Dr. Nachum Ulanovsky and postdoctoral fellow Dr. Yossi Yovel of the Institute’s Department of Neurobiology knew that bat sonar (or echolocation) obeys the same physical laws as the sonar on a submarine: the bats (or ships) emit a sound and listen for the echo, accurately judging the type and location of objects around them by the changes in the sound waves as they are reflected back. But there’s a tradeoff between detection and localization. The beam is most intense in the center, returning more information, which is good for detection; but localization is better done on the slope, where the intensity drops off as the signal spreads out, making it easier to follow movement across the beam.

Are bats able to choose the best echolocation strategy? Drs. Ulanovsky and Yovel, in collaboration with Dr. Cynthia Moss and research student Ben Falk from the University of Maryland, trained bats to locate and land – using echolocation alone – on a black sphere placed randomly in a completely dark room. A string of special microphones arrayed around the room’s walls traced the bats’ sound waves, while two infrared video cameras tracked their flight patterns.

The Egyptian fruit bats in Dr. Ulanovsky’s lab produce their signals in pairs of clicks. The researchers identified a pattern: the first set of double clicks was aimed left, and then right, and the next set was aimed right, and then left. As the bats closed in for a landing, they continued to throw their sound beams to alternate sides of the sphere, just where a mathematical formula for sonar sensing predicted they would be most effective. As the sphere was easily detectable, the bats' optimal strategy was one of localization. To test a situation in which detection was needed as well as localization, the scientists installed a large panel behind the sphere that echoed the sound waves back to the bats’ ears. Now they had to find the sphere’s echo amidst conflicting signals. This time, as the bats approached their target, they began to narrow their sweep and aim the beams more or less directly toward the sphere.

Many types of sensation, from echolocation in dolphins to sniffing in dogs to movements in the human eye, are based on some sort of active sensing. Drs. Ulanovsky and Yovel believe that what works for bats may well work for other animals: “sensing on the slope” could play a role in all of these and others.

For the past 10 years, the Weizmann Institute has been operating a research station in the semi-arid Yatir Forest, a pine forest at the edge of the Negev Desert. This station is part of a world-wide project composed of over 400 stations, called FLUXNET, which investigates the relationship between forests, the atmosphere, and climate around the globe. The contribution of the Yatir station, says Prof. Dan Yakir of the Department of Environmental Sciences and Energy Research, is unique as it “is one of very few in the semi-arid zone, which covers over 17% of the Earth’s land surface, and it has the longest record of the processes taking place in semi-arid forests.”

Forests counteract the greenhouse effect by removing heat-trapping CO₂ from the atmosphere and storing it in living trees. Over the years of measurement, Prof. Yakir’s group has found that the semi-arid forest, even though it’s not as luxuriant as the temperate forests farther north, is a surprisingly good carbon sink – better than most European pine forests and about on par with the global average. This was unexpected news for a forest sitting at the edge of a desert, and it indicated that there is real hope for the more temperate forests if things heat up under future global climate change scenarios.

But forests do more than just store CO₂, and Prof. Yakir, together with Dr. Eyal Rotenberg, decided to look at the larger picture – the total energy budget of a semi-arid forest. The first hint they had that other processes might be counteracting the cooling effect of CO₂ uptake came when they compared the forest’s albedo – how much sunlight is reflected from its surface back into space – with that of the nearby open shrub land. They found that the dark-colored forest canopy had a much lower albedo, absorbing quite a bit more of the sun’s energy than the pale, reflective surface of the surrounding areas. In a cloudless environment with high levels of solar radiation, albedo becomes an important factor in surface heating.

Next, the researchers looked at the mechanisms for “air conditioning” within the forest itself. To cool down, trees in wetter areas of the globe use water-cooled systems: They open pores in their leaves and simply let some of the water evaporate, drawing heat away in the process. But the semi-arid pine forest, with its limited water supply, is not built for evaporation. The scientists found that it uses an alternative, efficient, air-cooling system instead. As semi-arid forests are not as dense as their temperate counterparts, the air in the open spaces between the trees comes into contact with a large surface area, and heat can be easily transferred from the leaves to the air currents. This semi-arid air cooling system is quite efficient at cooling the treetops, and this cooling, in turn, leads to a reduction in infrared (thermal) radiation out into space. In other words, while the semi-arid forest can cool itself well enough to survive and take up carbon, it both absorbs more solar radiation energy (through the albedo effect) and retains more of this energy (by suppressing the emission of infrared radiation). Together, these effects turned out to be stronger than the scientists had expected. “Although the numbers vary with location and conditions,” says Prof. Yakir, “we now know it will take decades of forest growth before the ‘cooling’ CO₂ sequestration can overtake these opposing ‘warming’ processes.”

Prof. Yakir and Dr. Rotenberg then asked one more question: If planting semi-arid forests can in fact lead to warming over a good part of the forests’ life cycles, what happens when the opposite process – desertification – takes place? By applying what they had learned to existing data on areas that have turned to desert, they found that desertification, instead of hastening global warming, as is commonly thought, has actually mitigated it, at least in the short term. By reflecting sunlight and releasing infrared radiation, desertification of semi-arid lands over the past 35 years has slowed down global warming by as much as 20%, compared with the expected effect of the CO₂ rise over the same period. And in a world in which desertification is continuing at a rate of about six million hectares a year, that news might have a significant effect on how we estimate the rates and magnitude of climate change. Says Prof. Yakir, “Overall, forests remain hugely important climate stabilizers, not to mention the other ecological services they provide, but there are tradeoffs, such as those between carbon sequestration and surface radiation budgets, and we need to take these into consideration when predicting the future.”

To See or Not to See

How do the visual images we experience, which have no tangible existence, arise out of physical processes in the brain? New research at the Weizmann Institute of Science provides evidence, for the first time, that an “ignition” of intense neural activity underlies the experience of seeing.

In research recently published in the journal Neuron, Prof. Rafael Malach and research student Lior Fisch of the Weizmann Institute’s Department of Neurobiology worked with a neurosurgeon, Dr. Itzhak Fried of Tel Aviv Sourasky Medical Center, a distinguished team of medical doctors from the Center, and Weizmann Institute students. They asked a group of epileptic patients who had had electrodes clinically implanted into their brains in preparation for surgery to volunteer for some perceptual awareness tasks. The subjects looked at a computer screen, which briefly presented a “target” image – a face, house, or man-made object. This image was followed by a “mask” – a meaningless picture for distraction – at different time intervals after the target image had been presented. This allowed the experimenter to control the visibility of the images – the patients sometimes recognized the targets and sometimes failed to do so. By comparing the electrode recordings to the patients’ reports of whether they had correctly recognized the image or not, the scientists were able to pinpoint what was happening – and when and where – in the brain as transitions in perceptual awareness took place.

Says Prof. Malach, “We found that there was a rapid burst of neural activity occurring in the high-order visual centers of the brain – centers that are sensitive to entire images of objects, such as faces – whenever patients had correctly recognized the target image.” The scientists also found that the transition from not seeing to seeing happens abruptly. According to Mr. Fisch, “When the mask was presented too soon after the target image, it ‘killed’ the visual input signals, resulting in the patients being unable to recognize the object. The patients suddenly became consciously aware of the target image at a clear threshold, suggesting that the brain needs a specific amount of time to process the input signals in order for conscious perceptual awareness to be ignited.”

This study is the first of its kind to uncover strong evidence linking ignition of bursts of neural activity to perceptual awareness in humans. More questions remain: Is this the sole mechanism involved in the transition to perceptual awareness? To what extent is it a local phenomenon? By answering such questions, scientists might begin bridging the mysterious gap between the mind and the brain.

Prof. Rafael Malach’s research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the S. and J. Lurje Memorial Foundation; the Benjamin and Seema Pulier Charitable Foundation, Inc; Vera Benedek, Israel; and Mary Helen Rowen, New York, NY. Prof. Malach is the incumbent of the Barbara and Morris Levinson Professorial Chair in Brain Research.

The Pink Gene

Weizmann Institute Scientists Unravel the Genetic Secrets of a Pink Tomato

Many Far Eastern diners are partial to a variety of sweet, pink-skinned tomato. Dr. Asaph Aharoni of the Weizmann Institute’s Department of Plant Sciences has now revealed the gene that is responsible for producing these pink tomatoes. Dr. Aharoni’s research focuses on plants’ thin, protective outer layers, called cuticles, which are mainly composed of fatty, wax-like substances. In the familiar red tomato, this layer also contains large amounts of antioxidants called flavonoids that are the tomatoes’ first line of defense. Some of these flavonoids also give the tomato cuticles a bright yellow cast – the color component that is missing in the translucent pink skins of the mutants.

Using a lab system that is unique in Israel, and one of only a few in the world, Dr. Aharoni and his team are able to rapidly and efficiently identify hundreds of active plant substances called metabolites. A multidisciplinary approach developed over the past decade, known as metabolomics, enables them to create a comprehensive profile of all these substances in mutant plants and compare it with that of normal ones.

The research, carried out in Dr. Aharoni’s lab by Dr. Avital Adato, Dr. Ilana Rogachev, and research student Tali Mendel, showed that the differences between pink and red tomatoes go much deeper than skin color: the scientists identified about 400 genes whose activity levels are quite a bit higher or lower in the mutant tomatoes. The largest changes, appearing in both the plant cuticle and the fruit covering, were in the production of substances in the flavonoid family. The pink tomato also has less lycopene, a red pigment known to be a strong antioxidant that has been associated with reduced risk of cancer, heart disease, and diabetes. In addition, alterations in the fatty composition of the pink tomato’s outer layer caused its cuticle to be both thinner and less flexible that a regular tomato skin.

The researchers found that all of these changes can be traced to a mutation on a single gene known as SIMYB12. This gene acts as a “master switch” that regulates the activities of a whole network of other genes, controlling the amounts of yellow pigments as well as a host of other substances in the tomato. Says Dr. Aharoni, “Since identifying the gene, we found we could use it as a marker to predict the future color of the fruit in the very early stages of development, even before the plant has flowered. This ability could accelerate efforts to develop new, exotic tomato varieties, a process that can generally take over 10 years.”

Dr. Asaph Aharoni’s research is supported by the De Benedetti Foundation-Cherasco 1547 and the Willner Family Foundation. Dr. Aharoni is the incumbent of the Adolpho and Evelyn Blum Career Development Chair of Cancer Research.

Weizmann Institute Scientists Reveal
How Tendons Shape Developing Bones

Bones, muscles, and tendons work together to provide the perfect balance between stability and movement in the skeleton. Now, Weizmann Institute scientists have shown that this partnership begins in the embryo, when the bones are still taking shape. Their study, published in a recent issue of Developmental Cell, describes a previously unrecognized interaction between tendons and bones that drives the development of a strong skeletal system.

“Our skeleton, with its bones, joints, and muscle connections, serves us so well in our daily lives that we hardly pay attention to this extraordinary system,” says Dr. Elazar Zelzer of the Weizmann Institute’s Department of Molecular Genetics. “Although previous research has uncovered mechanisms that contribute to the development and growth of each component of this complex and wonderfully adaptable organ system, specific interactions between bones, muscles, and tendons that drive the assembly of the musculoskeletal system are not fully understood.”

Dr. Zelzer, research student Einat Blitz, Sergey Viukov and colleagues, were interested in uncovering the molecular mechanisms that regulate the formation of bone ridges – bony protuberances that provide a stable anchoring point for the tendons that connect muscles with bones. Bone ridges are critical for the skeleton’s ability to cope with the considerable mechanical stresses exerted by the muscles. The researchers used embryonic mouse skeletons to study a bone ridge called the deltoid tuberosity, located on the humerus bone in the arm.

They discovered, to their surprise, that rather than being shaped by processes within the skeleton, bone-ridge formation was directly regulated by tendons and muscles in a two-phase procedure. First, the embryonic tendons initiated bone-ridge formation by attaching to the skeleton. This interaction induced the tendon cells to express a specific protein called scleraxis, which in turn, led to the production of another protein, BMP4 – a molecule involved in the onset of bone formation. Blocking BMP4 production in tendon cells prevented deltoid tuberosity bone-ridge formation. In the second phase, the subsequent growth and ultimate size of the deltoid tuberosity was directly regulated by muscle activity.

The results demonstrate that tendons play an active role in initiating bone-ridge patterning. According to Dr. Zelzer, “These findings provide a new perspective on the regulation of skeletogenesis in the context of the musculoskeletal system, and they shed light on an important mechanism that underlies the assembly of this system.”

Dr. Elazar Zelzer’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Helen and Martin Kimmel Institute for Stem Cell Research; the Kirk Center for Childhood Cancer and Immunological Disorders; the David and Fela Shapell Family Center for Genetic Disorders Research; the estate of Rubin Feryszka; the estate of George Liebert; and the estate of Lela London. Dr. Zelzer is the incumbent of the Martha S. Sagon Career Development Chair.

More than a decade ago, Prof. Yair Reisner of the Weizmann Institute’s Department of Immunology pioneered a method for transplanting stem cells from family members who are a partial match. Based on these studies (in mice), he joined forces with Prof. Massimo F. Martelli, Head of the Hematology and Clinical Immunology Section at the University of Perugia, to demonstrate in more than 300 patients that the cure rate of these “mega dose” transplants is similar to that of transplants from matched, unrelated donors picked from international bone marrow donor registries. To combat the body’s tendency to reject the foreign cells, these stem cells are stripped of immune cells called T cells and given in high doses that overwhelm the host’s own immune system. Although removing donor T cells from the bone marrow reduces the risk of graft-versus-host disease – caused when the T cells attack the recipient’s tissues – the immune system is slow to recover after the transplant, leaving the patient at risk of serious infection. Doctors are faced with a difficult choice: Either remove the T cells from the bone marrow, increasing the risk of infection, or leave the T cells in the graft, putting the patient at risk for lethal graft-versus-host disease.

Prof. Martelli, working with Prof. Reisner, has now found a way to facilitate the recovery of the immune responses in recipients of T-cell-depleted bone marrow transplants. In a clinical trial, 25 of 26 leukemia and lymphoma patients who received mismatched mega-dose T-cell-depleted stem cell transplants from relatives showed prompt immune recovery, and their immune systems were functioning well several months later.

The scientists knew that certain regulatory T cells (T regs), rather than causing graft-versus-host disease, could actually help to prevent it in mice. T regs have also been shown to keep other immune responses in check, including preventing autoimmune attacks on the body’s own cells. In the present study, after purifying T regs from the donor’s blood, the cells were infused intravenously into the cancer patients, who had previously undergone standard radiation and chemotherapy treatments. Three days later, the patients received the donor stem cells, along with another kind of T cell – those that fight disease.

The patients who underwent this procedure showed quick, lasting improvements in immune activity, and most experienced no symptoms even though they received large doses of the T cells that are generally associated with lethal graft-versus-host disease.

Further follow-up on these patients and additional clinical trials will be needed before the procedure can be widely adopted, but these results strongly suggest that T regs used in mega-dose stem cells will further enhance the cure rate for bone marrow transplant patients without a matched donor in the family.

“It’s all about balance,” says team leader Dr. Avishay Gal-Yam of the Weizmann Institute of Science’s Department of Particle Physics and Astrophysics. “During a star’s lifetime, there’s a balance between the gravity that pulls its material inward and the heat produced in the nuclear reaction at its core, pushing it out. In a supernova we’re familiar with, of a star 10 to 100 times the size of the sun, the nuclear reaction begins with the fusion of hydrogen into helium, as in our sun. But the fusion keeps going, producing heavier and heavier elements, until the core turns to iron. Since iron doesn’t fuse easily, the reaction burns out, and the balance is lost. Gravity takes over and the star collapses inward, throwing off its outer layers in the ensuing shockwaves.”

The balance in a super-giant star is different. Here, the photons (light particles) are so hot and energetic, they interact to produce pairs of particles: electrons and their opposites, positrons. In the process, particles with mass are created from the massless photons, and this consumes the star’s energy. Again, things are thrown out of balance, but this time, when the star collapses, it falls in on a core of volatile oxygen, rather than iron. The hot, compressed oxygen explodes in a runaway thermonuclear reaction that obliterates the star’s core, leaving behind little but glowing stardust. “Models of ‘pair supernovae’ had been calculated decades ago,” says Dr. Gal-Yam, “but no one was sure these huge explosions really occur in nature. The new supernova we discovered fits these models very well.”

An analysis of the new supernova data led the scientists to estimate the star’s size at around 200 times the mass of the sun. This in itself is unusual, as observers had noted that the stars in our part of the universe seem to have a size limit of about 150 suns; some had even wondered if there was a physical constraint on a star’s girth. The new findings suggest that hyper-giant stars, while rare, do exist, and that even larger stars, up to 1,000 times the size of the sun, may have existed in the early universe. “This is the first time we’ve been able to analyze observations of such a massive exploding star,” says Dr. Paolo Mazzali of the Max Planck Institute for Astrophysics in Germany, who led the theoretical study of this object. “We were able to measure the amounts of new elements created in this explosion, including approximately five times the mass of our sun in highly radioactive, freshly synthesized nickel. Such explosions may be important factories for heavy metals in the universe.”

This massive supernova was found in a tiny galaxy only a hundredth the size of our own, and the scientists think that such dwarf galaxies could be natural harbors for the giant stars, somehow enabling them to surpass the 150-sun limit.

“Our discovery and analysis of this unique explosion has given us new insights into just how massive stars can get and how these stellar giants contribute to the makeup of our universe,” says Dr. Gal-Yam. “We hope to understand even more when we find additional examples from new surveys that we have recently begun to carry out, covering large, previously unexplored areas of the universe.”

Prof. Yonath’s research is driven by curiosity and ambition to better understand the world and our place within it. This research aims high: to understand one of the most complicated “machines” of the biological system.

The announcement of the award is especially meaningful to and joyous for the American Committee for the Weizmann Institute. One of the Committee’s most prominent leaders, Mrs. Helen Kimmel, together with her late husband, Martin, provided major funding for Prof. Yonath’s research for more than 20 years. Prof. Yonath is the Martin S. and Helen Kimmel Professor of Structural Biology; her research is supported by the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly. The special friendship developed between Prof. Yonath and Mrs. Kimmel over the years symbolizes the Weizmann partnership between science and philanthropy.

In the late 1970s, Prof. Yonath decided, when she was a young student at the Weizmann Institute, to take on the challenge of answering one of the key questions concerning the activities of live cells: to decipher the structure and mechanism of action of ribosomes – the cell’s protein factories. This was the beginning of a long scientific journey that has lasted decades, and required courage and devotion from the start. The journey began in a modest laboratory with a modest budget, and over the years increased to tens of researchers working under Prof. Yonath’s guidance.

This basic research, which began in an attempt to understand one of the principles of nature, eventually led to an understanding of how a number of antibiotics function, something that is likely to aid in the development of more advanced and effective antibiotics. This discovery will hopefully also help in the struggle against antibiotic-resistant bacteria, a problem recognized as one of the most central medical challenges of the 21st century.

Prof. Yonath can be considered a model of scientific vision for her courage in choosing a significant scientific question and devotion in realizing the goal to its end, which will hopefully broaden knowledge for the benefit of humanity.

BEYOND THE BASICS
“People called me a dreamer,” says Prof. Ada Yonath of the Structural Biology Department, recalling her decision to undertake research on ribosomes – the cell's protein factories. Solving the ribosome's structure would give scientists unprecedented insight into how the genetic code is translated into proteins; by the late 1970s, however, top scientific teams around the world had already tried and failed to get these complex structures of protein and RNA to take on a crystalline form that could be studied. Dreamer or not, it was hard work that brought results: Prof. Yonath and her colleagues made a staggering 25,000 attempts before they succeeded in creating the first ribosome crystals, in 1980.

And their work was just beginning. Over the next 20 years, Prof. Yonath and her colleagues would continue to improve their technique. In 2000, teams at the Weizmann Institute and the Max Planck Institute in Hamburg, Germany – both headed by Prof. Yonath – solved, for the first time, the complete spatial structure of both subunits of a bacterial ribosome. Science magazine counted this achievement among the ten most important scientific developments of that year. The next year, Prof. Yonath's teams revealed exactly how certain antibiotics are able to eliminate pathogenic bacteria by binding to their ribosomes, preventing them from producing crucial proteins.

Prof. Yonath's studies, which have stimulated intensive research worldwide, have now gone beyond the basic structure. She has revealed in detail how the genetic information is decoded, how the ribosome's inherent flexibility contributes to antibiotic selectivity, and the secrets of cross-resistance to various antibiotic families. Her findings are crucial for developing advanced antibiotics.

Graduate student Yaara Yeshurun, together with Profs. Noam Sobel and Yadin Dudai of the Institute’s Department of Neurobiology, thought that the key might not necessarily lie in childhood, but rather in the first time a smell is encountered in the context of a particular object or event. In other words, the initial association of a smell with an experience will somehow leave a unique and lasting impression in the brain.

To test this idea, the scientists devised an experiment: First, in a special smell laboratory, subjects viewed images of 60 objects, each presented simultaneously with either a pleasant or an unpleasant odor generated in a machine called an olfactometer. Next, the subjects were put in a functional magnetic resonance imaging (fMRI) scanner to measure their brain activity as they reviewed the images they’d seen and attempted to remember which odor was associated with each. Then, the whole test was repeated – images, odors, and fMRI – with the same images, but different odors accompanying each. Finally, the subjects came back one week later, to be scanned in the fMRI again. They viewed the objects one more time and were asked to recall the odors they associated with them.

The scientists found that after one week, even if the subject recalled both odors equally, the first association revealed a distinctive pattern of brain activity. The effect was seen whether the smell was pleasant or unpleasant. This unique representation showed up in the hippocampus, a brain structure involved in memory, and in the amygdala, a brain structure involved in emotion. The pattern was so profound, it enabled the scientists to predict which associations would be remembered just by looking at the brain activity within these regions following the initial exposure. The scientists could look at the fMRI data on the first day of the experiment and predict which associations would come up a week later. To see if other sensory experiences might share this tendency, the scientists repeated the entire experiment using sounds rather than smells; they found that sounds did not arouse a similar distinctive first-time pattern of activity. In other words, these results were specific to the sense of smell. “For some reason, the first association with smell gets etched into memory,” says Prof. Sobel, “and this phenomenon allowed us to predict what would be remembered one week later based on brain activity alone.”

Adds Ms. Yeshurun: “As far as we know, this phenomenon is unique to smell. Childhood olfactory memories may be special not because childhood is special, but simply because those years may be the first time we associate something with an odor.”

The survey, published in the November issue of The Scientist, reviewed the entries of more than 2,350 qualified respondents. Survey respondents represented 119 institutions: 94 from the U.S. and 25 from abroad. The respondents were asked to assess their working environment by indicating their level of agreement with 38 criteria in eight different areas, while also specifying how important each factor was to them. Research resources, pay, peers, job satisfaction, and tenure and promotion were among the eight categories included in the survey.

Princeton University was ranked the best place to work in academia in the U.S. and the Max Planck Institute of Molecular Cell Biology and Genetics was ranked the top international academic institution. The magazine determined that, overall, respondents focused on collaboration, team building, and unique funding opportunities as important work environment factors.

The Scientist magazine provides coverage of the latest developments in the life sciences. This year’s survey results, as well as in-depth analysis, full-color charts, methodology, and past survey results can be viewed at www.the-scientist.com/bptw.

The Weizmann Institute of Science, noted for its wide-ranging exploration of the natural and exact sciences, is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

As part of her philanthropic leadership appointment, Ms. Merlo will direct efforts to raise awareness and expand the reach of the Weizmann Institute of Science, while also championing the Institute’s crucial work to address the biggest challenges facing humanity. She will aim to further involve current New York supporters and recruit new supporters. Ms. Merlo will succeed Bruce Pollack, who served as Chair of the New York Region’s Executive Committee for four years.

Throughout her 33 years of employment with Philip Morris USA (PMUSA), Ms. Merlo held a variety of positions, including Vice President of Marketing Services, where she was responsible for Marketing Programs such as Event Sponsorship and Database Development. She also served as a Director of Brand Management.

Prior to her retirement in 2003, Ms. Merlo was Senior Vice President of Corporate Affairs at PMUSA. She directed internal and external communications; public affairs activities; corporate responsibility planning and programs; and consumer affairs and community relations, including charitable grants on behalf of the company. She also served as senior spokesperson.

"Ellen Merlo is among the American Committee’s most devoted and active leaders," Larry Blumberg, national Chairman of the organization, said. "I am delighted that she has agreed to lead the New York Region. Ellen’s passion for the Weizmann Institute is contagious, and her ability to communicate the importance of our mission is so valuable as we seek to expand our circle of supporters in New York and beyond."

Her appointment to the leadership position recognizes Ms. Merlo’s long-standing dedication to the Weizmann Institute of Science. She has been a New York Regional Executive Committee member, a member of the American Committee’s Board of Directors and its Executive Committee, and has been nominated as a member of the International Board of Governors of the Weizmann Institute of Science. Ms. Merlo also recently chaired a national task force for the American Committee on positioning and visibility, and at the 2009 Global Gathering in Los Angeles, she was inducted into the prestigious President’s Circle. Since her retirement, Ms. Merlo has taken on active roles in other philanthropic organizations as well, including serving as Vice President of the Baron de Hirsch Fund, and heading up her own charitable foundation, the Pearl Welinsky Merlo Foundation.

TrkA is a particular cell receptor well known for its "pro-life advocacies": when nerve growth factor proteins bind to TrkA receptors, it activates the receptors into promoting the growth and survival of neurons.

So when Fainzilber, together with Ph.D. student Liraz Harel, postdoctoral student Dr. Barbara Costa, technician Zehava Levy, and former Ph.D. student Dr. Marianna Tcherpakov carried out screening tests to identify other molecules involved in this signaling cascade, it took them by surprise to learn that TrkA may not be who it seems. They found that if TrkA teams up with another molecule called CCM2 – the newly identified player in this signaling cascade – they become "partners in crime," with TrkA turning into a cell killer.

However, though paradoxical, this atypical behavior may actually be rooting for life after all. This idea comes from findings concerning pediatric tumors of neural origin; specifically, medulloblastoma – the most common malignant brain tumor and the second most common malignancy among children less than 20 years of age, and neuroblastoma – the most common extracranial solid cancer in childhood.

Neuroblastoma displays unusual behavior, being one of the few human malignancies known to demonstrate spontaneous regression in some cases, but nobody knows how or why. Studies have shown that the tumors with positive prognosis usually express TrkA, while aggressive forms of the tumor do not. However, how TrkA induces tumor regression is yet unknown and the mechanism was an enigma.

What if CCM2 was the missing piece to the tumor regression puzzle? Together with a group of scientists in Germany who were conducting a large-scale gene expression study in tumors from neuroblastoma patients, they checked the expression levels of CCM2 and TrkA from the patient samples collected. The results were clear- cut: TrkA and CCM2 were always expressed together in certain tumors – those that showed the highest incidences of regression and patient survival.

The scientists confirmed their results by blocking the expression of either TrkA or CCM2 in some cells, which resulted in cell survival. On the other hand, by introducing CCM2 to cells lacking it, cell death was induced if TrkA was also present, suggesting that this mechanism could lead to tumor regression.

This research, recently published in Neuron, is one of the first to elucidate this paradoxical "pro-cell death" behavior of TrkA and the first to identify CCM2 as a crucial accessory in this particular pathway, as well as describing in detail just how these two molecules interact.

The award ceremony will take place on September 14, 2009, in the Schmidt Lecture Hall at the Weizmann Institute of Science. These awards, which have been granted within the framework of the Weizmann Institute’s National Postdoctoral Award Program for Advancing Women in Science, is intended to help young women conduct postdoctoral studies at leading universities abroad, assisting them in pursuing a career in the sciences: natural (physics, chemistry, and the life sciences) or exact (mathematics and computer science). The goal of the program is to begin closing the gap between the numbers of male and female scientists in the highest ranks of academia.

Recipients of the awards are selected by a special Feinberg Graduate School committee, headed by the Weizmann Institute President’s Adviser for Advancing Women in Science, Prof. Adi Kimchi.

Five of this year’s recipients completed their doctoral studies at the Hebrew University of Jerusalem, three at the Weizmann Institute of Science, two at the Technion – Israel Institute of Technology, and one at Tel Aviv University.

The program, now in its third year, is aimed at helping young women scientists to overcome the main bottleneck in their professional advancement – conducting postdoctoral studies abroad. The award provides various incentives – economic, as well as social and professional – and helps to alleviate the pressure on women, especially those who are married with young children, by financing their studies abroad for two years.

The ultimate goal of the award is to encourage women who are interested in pursuing a scientific career in Israel, with the intention of producing a future cadre of women leaders within Israeli research establishments.

Shapiro and his team at Weizmann introduced the first autonomous programmable DNA computing device in 2001. So small that a trillion fit in a drop of water, that device was able to perform such simple calculations as checking a list of 0s and 1s to determine if there was an even number of 1s. A newer version of the device, created in 2004, detected cancer in a test tube and released a molecule to destroy it. Besides the tantalizing possibility that such biology-based devices could one day be injected into the body - a sort of "doctor in a cell" locating disease and preventing its spread - biomolecular computers could conceivably perform millions of calculations in parallel.

Now, Shapiro and his team, in a paper published online today in Nature Nanotechnology, have devised an advanced program for biomolecular computers that enables them to “think” logically. The train of deduction used by this futuristic device is remarkably familiar. It was first proposed by Aristotle over 2000 years ago as a simple if…then proposition: “All men are mortal. Socrates is a man. Therefore, Socrates is mortal.” When fed a rule (All men are mortal) and a fact (Socrates is a man), the computer answered the question “Is Socrates Mortal?” correctly. The team went on to set up more complicated queries involving multiple rules and facts, and the DNA computing devices were able to deduce the correct answers every time.

At the same time, the team created a compiler - a program for bridging between a high-level computer programming language and DNA computing code. Upon compiling, the query could be typed in something like this: Mortal(Socrates)?. To compute the answer, various strands of DNA representing the rules, facts and queries were assembled by a robotic system and searched for a fit in a hierarchical process. The answer was encoded in a flash of green light: Some of the strands had a biological version of a flashlight signal - they were equipped with a naturally glowing fluorescent molecule bound to a second protein which keeps the light covered. A specialized enzyme, attracted to the site of the correct answer, removed the “cover” and let the light shine. The tiny water drops containing the biomolecular data-bases were able to answer very intricate queries, and they lit up in a combination of colors representing the complex answers.

Born in San Salvador and raised in Latin America and Africa, Baroness Ariane de Rothschild, a French and German citizen, has over twenty years of finance and banking experience. She now holds various board positions in Geneva and in Paris with the LCF Rothschild Group, as well as serving as chairwoman of BeCitizen, an advisory company in structured finance and fund management for the environment sector. In addition, she devotes much of her time to the Edmond and Benjamin de Rothschild Foundations, in which her personal interests mesh with the family’s commitment to education and philanthropic innovation in the arts and culture, medical research, environment, women’s empowerment, intercultural dialogue and social entrepreneurship.

The Rothschild-Weizmann Program for Excellence in Science Teaching, which began operating at the Weizmann Institute last year, grants master’s degrees to outstanding science and math teachers in middle and high schools. For those who already have advanced science degrees, the program also offers a track in developing educational initiatives, which combines practical experience with scientific research. The prestigious Rothschild-Weizmann Program deepens and broadens the teachers’ scientific knowledge, familiarizes them with the newest approaches to science education, introduces them to research in the field of science teaching and provides them with experience in leading original educational initiatives. Participants in the program receive study grants and an exemption from tuition, and they continue to teach in parallel to their studies. The first 50 teachers to join the program are now finishing their first year of studies.

Dr. Schwartz will promote the important work of the Weizmann Institute. He seeks to further engage the vibrant Southern California area, one of the American Committee’s most active and key regions in the U.S. He succeeds Lon Morton of Calabasas.

Dr. Schwartz is a board-certified physician and “serial” entrepreneur. He was founder and CEO of Continuing Medical Education (CME) Inc., and it was under his stewardship that the company became the largest proprietary provider of clinical information for U.S. healthcare providers. In 2004, five years after selling CME, he co-founded the Value Investing Congress, which provides high-quality, practical information on investing to hedge fund managers and ultra high-net-worth investors.

“We are delighted to have Dr. Schwartz at the helm of one of the most important regional areas for the American Committee,” Larry Blumberg, National Chairman, said. “Working closely with the Southern California volunteer leadership and with Janis Rabin, Executive Director of the region, we know that his passionate commitment to the Weizmann Institute will help us reach even greater heights of success in Los Angeles and beyond.”

Dr. Schwartz’s appointment to the chairmanship follows years of support of the Weizmann Institute of Science: a member of the American Committee Board of Directors, Executive Committee, and the Weizmann Institute’s International Board of Governors, he served as Chair of the Global Gathering Gala–the highlight of the American Committee’s yearly national event. He and his wife, Vera, are also members of the prestigious President’s Circle. Dr. Schwartz is a devoted husband, father, and grandfather. He resides in Pacific Palisades.

E. coli bacteria, for instance, which normally cruise harmlessly down the digestive tract, encounter a number of different environments on their way. In particular, they find that one type of sugar – lactose – is invariably followed by a second sugar – maltose – soon afterward. Pilpel and his team in the Molecular Genetics Department checked the bacteria’s genetic response to lactose and found that, in addition to the genes that enable it to digest lactose, the gene network for utilizing maltose was partially activated. When they switched the order of the sugars, giving the bacteria maltose first, there was no corresponding activation of lactose genes, implying that bacteria have naturally “learned” to get ready for a serving of maltose after a lactose appetizer.

Another microorganism that experiences consistent changes is wine yeast. As fermentation progresses, sugar and acidity levels change, alcohol levels rise, and the yeast’s environment heats up. Although the system was somewhat more complicated than that of E. coli, the scientists found that when the wine yeast feel the heat, they begin activating genes for dealing with the stresses of the next stage. Further analysis showed that this anticipation and early response is an evolutionary adaptation that increases the organism’s chances of survival.

Ivan Pavlov first demonstrated this type of adaptive anticipation, known as a conditioned response, in dogs in the 1890s. He trained the dogs to salivate in response to a stimulus by repeatedly ringing a bell before giving them food. In the microorganisms, says Pilpel, “evolution over many generations replaces conditioned learning, but the end result is similar.” “In both evolution and learning,” says Mitchell, “the organism adapts its responses to environmental cues, improving its ability to survive.” Romano: “This is not a generalized stress response, but one that is precisely geared to an anticipated event.” To see whether the microorganisms were truly exhibiting a conditioned response, Pilpel and Mitchell devised a further test for the E. coli based on another of Pavlov’s experiments. When Pavlov stopped giving the dogs food after ringing the bell, the conditioned response faded until they eventually ceased salivating at its sound. The scientists did something similar, using bacteria grown by Dr. Erez Dekel, in the lab of Prof. Uri Alon of the Weizmann Institute’s Molecular Cell Biology Department, in an environment containing the first sugar, lactose, but not following it up with maltose. After several months, the bacteria had evolved to stop activating their maltose genes at the taste of lactose, only turning them on when maltose was actually available.

“This showed us that there is a cost to advanced preparation, but that the benefits to the organism outweigh the costs in the right circumstances,” says Pilpel. What are those circumstances? Based on the experimental evidence, the research team created a sort of cost/benefit model to predict the types of situations in which an organism could increase its chances of survival by evolving to anticipate future events. The researchers are already planning a number of new tests for their model, as well as different avenues of experimentation based on the insights they have gained.

Pilpel and his team believe that genetic conditioned response may be a widespread means of evolutionary adaptation that enhances survival in many organisms – one that may also take place in the cells of higher organisms, including humans. These findings could have practical implications, as well. Genetically engineered microorganisms for fermenting plant materials to produce biofuels, for example, might work more efficiently if they gained the genetic ability to prepare themselves for the next step in the process.

Professor Ephraim Katzir, fourth President of Israel and one of the founding faculty members of the Weizmann Institute of Science, was born in Kiev, the Ukraine, in 1916. His parents, Yehuda and Tsila Katchalski, brought him to British-ruled Palestine in 1922. Following high school in Jerusalem, he enrolled in the Hebrew University of Jerusalem where he studied botany, zoology and bacteriology before finally concentrating on biochemistry and organic chemistry. In 1941, he completed his Ph.D. thesis on simple synthetic polymers of amino acids and continued his education at the Polytechnic Institute of Brooklyn, Columbia University and Harvard University.

While studying in Jerusalem he participated in the first non-commissioned officers’ course given by the underground Haganah. Later, Katzir became deeply involved in the Israel Army’s Science Corps, Hemed, founded at the start of the 1948 War of Independence, and for a time commanded it as a lieutenant colonel.

At the war’s end, in 1949, Katzir and his brother Aharon, also a scientist, joined the Weizmann Institute. Ephraim founded and headed the Biophysics Department, while Aharon headed the Polymer Research Department until his tragic death at the hands of terrorists at Ben-Gurion Airport in 1972.

Ephraim Katzir’s initial research centered on polyamino acids – synthetic models that facilitate the study of proteins. His pioneering studies contributed to the deciphering of the genetic code, the production of synthetic antigens and the clarification of the various steps of immune responses. The understanding of polyamino acid properties led, among other things, to Weizmann scientists’ development of Copaxone, a drug used worldwide for the treatment of multiple sclerosis.

Another major success was in immobilizing enzymes. Katzir developed a method for binding enzymes, which speed up numerous chemical processes, to a variety of surfaces and molecules. The method laid the foundations for what is now called enzyme engineering, which plays an important part in the food and pharmaceutical industries. For example, it is used to produce fructose-enriched corn syrup and semi-synthetic penicillins.

Along with his scientific research, Professor Katzir was profoundly involved in the social and educational aspects of science. He headed a governmental committee for the formulation of a national scientific policy, trained a generation of younger scientists, translated important material into Hebrew and helped to establish a popular science magazine. He served as Chief Scientist of the Israel Defense Ministry and Chairman of the Society for the Advancement of Science in Israel, the Israel Biochemical Society, the National Council for Research and Development and the Council for the Advancement of Science Education. He headed the National Biotechnology Council and was President of the World ORT Union.

In 1973, Katzir was elected fourth President of the State of Israel, a position he held until 1978. (It was upon becoming President that he changed his last name from Katchalski to Katzir.) During his term he paid special attention to the problems of society and education and was consistently concerned with learning more about all sectors of the population.

Upon completing his term of office, he returned to research at the Weizmann Institute and was named Institute Professor, a prestigious title awarded by Weizmann faculty and administration to outstanding scientists who made significant and meaningful contributions to science or to the State of Israel. He also devoted himself to the promotion of biotechnological research in Israel and founded the Department of Biotechnology at Tel Aviv University. The creation of this department was a continuation of his previous efforts to establish science-based industries in Israel: he had helped create several companies based on the fruits of scientific research.

In the later years of his scientific career Prof. Katzir turned to new areas of research. In one project, he headed a team of Weizmann scientists that won an international contest for computer modeling of proteins. In another study, he was part of an interdisciplinary Institute team that revealed an important aspect of snake venom’s effects on the body.

Katzir authored hundreds of scientific papers and served on the editorial and advisory boards of numerous scientific journals. International scientific symposia were held in Rehovot and Jerusalem to celebrate his 60th, 70th and 80th birthdays.

Prof. Katzir was a member of the Israeli Academy of Sciences and Humanities and of numerous other learned bodies in Israel and abroad, including The Royal Institution of Great Britain, The Royal Society of London, the National Academy of Sciences of the United States, the Academie des Sciences in France, the Scientific Academy of Argentine and the World Academy of Art and Science. He was visiting professor at Harvard University, Rockefeller University, University of California at Los Angeles and Battelle Seattle Research Center.

In addition, Katzir was awarded the Rothschild and Israel Prizes in Natural Sciences, the Weizmann Prize, the Linderstrom Land Gold Medal, the Hans Krebs Medal, the Tchernikhovski Prize for scientific translations, the Alpha Omega Achievement Medal and the Engineering Foundation’s International Award in Enzyme Engineering. He was the first recipient of the Japan Prize and was appointed to France’s Order of Legion of Honor. He received honorary doctorates from more than a dozen institutions of higher learning in Israel and around the world, including Harvard University, Northwestern University, McGill University, University of Oxford and the Technion-Israel Institute of Technology.

The magazine Annual Reviews quoted Katzir thus: “I have had the opportunity to devote much of my life to science. Yet my participation over the years in activities outside science has taught me there is life beyond the laboratory. I have come to understand that if we hope to build a better world, we must be guided by the universal human values that emphasize the kinship of the human race: the sanctity of human life and freedom, peace between nations, honesty and truthfulness, regard for the rights of others, and love of one’s fellows.”

Joshua Karlin brings to the position a unique and exciting set of skills and experiences. Most recently, as president of Aliya Marketing & Fundraising Group, Mr. Karlin acted as a marketing and fundraising consultant to U.S. and Israeli nonprofits and businesses. Mr. Karlin’s entrepreneurial talents first came to the fore at the beginning of his professional career, when he co-founded Ashley’s Ice Cream in New Haven, Conn. He later sold the company, which had more than 100 employees and seven stores. His background in philanthropy extends back over 10 years: Mr. Karlin acted as Director of Development and Endowment at the Jewish Federation of Rhode Island and as Director of Development at Tufts University Hillel. He also served on the National Committee on Planned Giving and is past president of the Planned Giving Council of Rhode Island.

As executive director of the Washington, D.C. Region, Mr. Karlin will advocate for the Weizmann Institute of Science and advance its mission of “Science for the Benefit of Humanity” in the District of Columbia and the greater Washington, D.C. metro area. He will focus his efforts on enhancing and cultivating relationships with major donors in the area and recruiting new and diverse volunteer leadership in order to promote visibility of and support for the Weizmann Institute of Science.

“The Washington, D.C. community is a vibrant and important part of our larger Weizmann Institute family. We look forward to seeing the Washington, D.C. Region grow and flourish under Joshua’s leadership,” Marshall S. Levin, Executive Vice President and CEO of the American Committee for the Weizmann Institute of Science, said.

Mr. Karlin received his B.A. cum laude from Tufts University.

Ms. Imberman, a member of the Weizmann President’s Circle and a renowned graphologist, has provided funding to the American Committee for the past three years to support the production of films that accentuate the significance and benevolence of supporting research at the Weizmann Institute. The films have been screened annually at the New York Region Gala dinner, and are also viewed by Weizmann Institute supporters across the country.

“We are proud that Arlyn Imberman’s creative vision has been recognized with two prestigious Telly awards,” Marshall S. Levin, Executive Vice President and CEO of the American Committee, said. “It was Arlyn’s goal to share the core philanthropic values and beliefs of Weizmann Institute supporters with a larger audience, and we have achieved that by producing these poignant videos. We are grateful for her generous support and creative guidance.”

The Dor L’ Dor film is a 7-minute discourse with three families who have made supporting the Weizmann Institute a priority over several generations. In the film, the Blumberg, Pickman, and Gurwin families explain their enthusiasm for the Weizmann Institute’s cutting-edge multidisciplinary research, talented scientists, and pursuit to solve some of the most difficult challenges facing humanity. Each family also addresses the value of philanthropy and the importance of passing down the dedication to philanthropic activities, including a commitment to supporting Weizmann, from one generation to the next.

A similar film, also produced by Ms. Imberman, was previously recognized with a Silver Telly, the top honor. The 29th Annual Telly Awards was one of the most competitive thus far, with 13,500 entries from all 50 states and countries around the world. The Telly Awards is the premier award honoring outstanding local, regional, and cable TV commercials and programs; the finest film and video productions; and groundbreaking web commercials, video, and film. More than 40 accomplished industry professionals, each a past Silver Winner, compose the prestigious Telly Awards judging panel. Entries do not compete against each other; instead, each entry is individually judged against a high standard of merit.

The winning films were created for the American Committee by Twenty-Two Productions, an award-winning New York City-based film production company, led by Dean Silvers and Marlen Hecht.

One can have a dream, two can make that dream so real, goes a popular song. Now a Weizmann Institute study has revealed that it takes two to perform an essential form of DNA repair.

Prof. Zvi Livneh of the Weizmann Institute’s Biological Chemistry Department has been studying DNA repair for some two decades: “Considering that the DNA of each cell is damaged about 20,000 times a day by radiation, pollutants, and harmful chemicals produced within the body, it’s obvious that without effective DNA repair, life as we know it could not exist. Most types of damage result in individual mutations – genetic ‘spelling mistakes’ – that are corrected by precise, error-free repair enzymes. Sometimes, however, damage results in more than a mere spelling mistake; it can cause gaps in the DNA, which prevent the DNA molecule from being copied when the cell divides, much like an ink blot or a hole on a book page interferes with reading. So dangerous are these gaps that the cell resorts to a sloppy but efficient repair technique to avoid them: it fills in the missing DNA in an inaccurate fashion. Such repair can save the cell from dying, but it comes at a price: this error-prone mechanism, discovered at the Weizmann Institute and elsewhere about a decade ago, is a major source of mutations.”

In a recent study he conducted with graduate students Sigal Shachar and Omer Ziv, as well as researchers from the US and Germany, Livneh revealed how the error-prone repair works. The team found that such repair proceeds in two steps and requires two types of enzymes, belonging to the family of enzymes called DNA polymerases, which synthesize DNA. First, one repair enzyme, “the inserter,” does its best to fit a genetic “letter” into the gap, opposite the damaged site in the DNA molecule; several enzymes can perform this initial step, which often results in the insertion of an incorrect genetic letter. Next, another enzyme, “the extender,” helps to restore regular copying of DNA by attaching additional DNA letters after the damaged site; only one repair enzyme is capable of performing this vital second step. These findings were published recently in the EMBO Journal.

Understanding how this major form of DNA repair works can have significant clinical implications. Since defects in this process increase the risk of cancer, clarifying its nuts and bolts might one day make it possible to enhance it in people whose natural DNA repair is deficient. In addition, manipulating this mechanism can improve the effectiveness of cancer drugs. Cancer cells can resist chemotherapy by exploiting their natural repair mechanisms, and blocking these mechanisms may help overcome this resistance, leading to a targeted destruction of the cancerous tumor.

True Grit Sea Urchins’ Digging Teeth are Designed to Stay Sharp

Sea urchins dig themselves hiding holes in the limestone of the ocean floor using teeth that don’t go blunt. Weizmann Institute scientists have now revealed their secrets, which might give engineers insights into creating ever-sharp tools or mechanical parts.

The urchins dig holes to fit their globular bodies using their five teeth, which, like those of rodents, are ground down at the tip but continue to grow on the other end throughout the animals’ lives. The amazing part, however, is that the urchins’ teeth, which need to be harder and stronger than the rocky limestone being dug out, are themselves made almost entirely of calcite – the same calcite that makes up much of the limestone. How is this possible? In a series of studies spanning more than a decade, Profs. Steve Weiner and Lia Addadi of Weizmann’s Structural Biology Department have discovered that the urchins’ secret lies in a combination of ingenious design strategies. The latest of these studies, conducted with postdoctoral fellow Yurong Ma and graduate student Yael Politi and in collaboration with Prof. Pupa Gilbert and Dr. Rebecca Metzler of the University of Wisconsin; Drs. Barbara Aichmayer, Oskar Paris, and Peter Fratzl from the Max Planck Institute of Colloids and Interfaces in Potsdam, Germany; and Dr. Anders Meibom from the Muséum National D’Histoire Naturelle in Paris, France, was reported recently in the Proceedings of the National Academy of Sciences (PNAS).

The scientists found that the sea urchins’ teeth contain crystals of magnesium calcite, which are smaller, harder, and denser than those of pure calcite; they are concentrated at the grinding tip of the tooth, particularly in the tip’s center, where the most force is being exerted in the course of grinding. What holds these crystals at the center of the tip is a matrix of larger and softer calcite crystals. While in most such materials a matrix of hard fibers contains a softer filling, the reverse is true for the urchins’ tooth: a matrix of relatively soft calcite fibers holds the harder magnesium calcite crystals, which allows these crystals to spread over the entire surface of the tooth. The presence of magnesium calcite crystals acts like sandpaper that helps to grind the rock down.

In the latest study, the researchers used x-ray photoelectron emission spectromicroscopy and other high-resolution imaging methods to uncover yet another amazing structural feature of sea urchin tooth design. They found that all the crystalline elements that make up the tooth are aligned in two different arrays, and that these arrays are “interdigitated,” or interlocked like the fingers of folded hands, just at the tip of the tooth, where most of the wear occurs. The scientists believe that interlocking produces a notched, serrated ridge resembling that of a carpenter’s file. This ridge is self-sharpening: as the tooth is being ground down, the crystalline layers break in such a way that the ridge always stays corrugated.

Prof. Lia Addadi’s research is supported by the Clore Center for Biological Physics; the Ilse Katz Institute for Material Sciences and Magnetic Resonance Research; the Helen and Martin Kimmel Center for Nanoscale Science; the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly; and the Carolito Stiftung. Prof. Addadi is the incumbent of the Dorothy and Patrick Gorman Professorial Chair.

For the scientific paper, please see: www.pnas.org/content/106/15/6048.full?sid=39c9feb7-911b-4679-bc95-f752b74e0dcd

Weizmann Institute Scientists Show: White Blood Cells Move Like Millipedes

How do white blood cells – immune system “soldiers” – get to the site of infection or injury? To do so, they must crawl swiftly along the lining of the blood vessel – gripping it tightly to avoid being swept away in the blood flow – all the while searching for temporary “road signs” made of special adhesion molecules that let them know where to cross the blood vessel barrier so they can get to the damaged tissue.

In research recently published in the journal Immunity, Prof. Ronen Alon and his research student Ziv Shulman of the Weizmann Institute’s Immunology Department show how white blood cells advance along the length of the endothelial cells lining the blood vessels. Current opinion maintains that immune cells advance like inchworms, but Alon’s new findings show that the rapid movement of the white blood cells is more like that of millipedes. Rather than sticking front and back, folding and extending to push itself forward, the cell creates numerous tiny “legs” no more than a micron in length – adhesion points, rich in adhesion molecules (named LFA-1) that bind to partner adhesion molecules present on the surface of the blood vessels. Tens of these legs attach and detach in sequence within seconds – allowing them to move rapidly while keeping a good grip on the vessels’ sides.

Next, the scientists turned to the Institute’s Electron Microscopy Unit. Images produced by transmission and scanning electron microscopes, taken by Drs. Eugenia Klein and Vera Shinder, showed that upon attaching to the blood vessel wall, the white blood cell legs “dig” themselves into the endothelium, pressing down on its surface. The fact that these legs – which had been thought to appear only when the cells leave the blood vessels – are used in crawling the vessel lining suggests that they may serve as probes to sense exit signals. The researchers found that the shear force created by the blood flow was necessary for the legs to embed themselves. Without the thrust of the rushing blood, the white blood cells couldn’t sense the exit signals or get to the site of the injury. These results explain Alon’s previous findings that the blood’s shear force is essential for the white blood cells to exit the blood vessel wall. The present study suggests that shear forces cause their adhesion molecules to enter highly active states. The scientists believe that the tiny legs are trifunctional: used for gripping, moving, and sensing distress signals from the damaged tissue.

In future studies, the scientists plan to check whether it is possible to regulate aggressive immune reactions (such as in autoimmune diseases) by interrupting the “digging” of immune cell legs into the endothelium. They also plan to investigate whether cancerous blood cells metastasize through the blood stream using similar mechanisms in order to exit the blood vessels and enter different tissues.

Dr. Maya Schuldiner of the Weizmann Institute’s Department of Molecular Genetics, one of the 34 scientists who joined the Institute faculty during the past three years, said: “Six months ago, my husband Oren (who has also become a senior scientist at the Weizmann Institute) and I returned to Israel after our postdoctoral studies in San Francisco. Even though we enjoyed living in this beautiful city which has some of the best universities in the world, not a day went by that we didn’t miss Israel. Other Israelis we met there also missed home. To my disappointment, and to theirs, many of them will not return home, as this would jeopardize their job satisfaction, their standard of living, and the level of education for their children. The Weizmann Institute enables us to engage in world-class science—with the same equipment and under the same conditions as those available at the best universities in the world—without giving up on our identities, without losing the possibility of raising our children as Israelis, and without having to miss our country. If only as many young Israeli scientists as possible could be as lucky as we are, and be able to return home.”

The Weizmann Institute of Science, named after Dr. Chaim Weizmann, has invested substantial resources and effort in providing young scientists the ability to conduct research in Israel, in an attempt to counteract the phenomenon known as “brain drain”: young Israeli scientists going abroad to do their postdoctoral research and deciding to remain overseas after receiving attractive job offers. The Weizmann Institute has spent some $30 million offering positions to 34 outstanding young Israeli scientists and financing their absorption into the Institute: establishing a laboratory, purchasing research equipment, and generating salaries for several laboratory workers and students. The Institute also funded each scientist’s move back to Israel, including transportation home for his or her entire family. Most scientists were offered on-campus housing—a particularly important component for those spending long hours in the lab. A kindergarten run by a steering committee comprising mainly scientist mothers was built on the Institute campus for the benefit of the many young scientists who are parents of preschool-age children. The kindergarten serves meals to the children and provides them with care till the late afternoon.

Now, a unique approach developed by Prof. David Milstein and colleagues in the Weizmann Institute’s Organic Chemistry Department provides important steps in overcoming this challenge. The team has demonstrated a new mode of bond generation between oxygen atoms, and even defined the mechanism by which it takes place. In fact, it is the generation of oxygen gas by the formation of a bond between two oxygen atoms originating from water molecules that proves to be the bottleneck in the water splitting process. Their results have recently been published in Science.

Nature, by taking a different path, has evolved a very efficient process: photosynthesis – carried out by plants – the source of all oxygen on Earth. Although there has been significant progress towards the understanding of photosynthesis, just how this system functions remains unclear; vast worldwide efforts have been devoted to the development of artificial photosynthetic systems based on metal complexes that serve as catalysts, with little success. (A catalyst is a substance that is able to increase the rate of a chemical reaction without getting used up.)

The new approach devised by the Weizmann team is divided into a sequence of reactions, which leads to the liberation of hydrogen and oxygen in consecutive thermal- and light-driven steps, mediated by a unique ingredient – a special metal complex that Milstein’s team designed in previous studies. Moreover, the one that they designed – a metal complex of the element ruthenium is a “smart” complex in which the metal center and the organic part attached to it cooperate in the cleavage of the water molecule.

The team found that, upon mixing this complex with water, the bonds between the hydrogen and oxygen atoms break, with one hydrogen atom binding to its organic part, while the remaining hydrogen and oxygen atoms (OH group) bind to its metal center.

This modified version of the complex provides the basis for the next stage of the process: the “heat stage.” When the water solution is heated to 100˚C, hydrogen gas is released from the complex – a potential source of clean fuel – and another OH group is added to the metal center.

“But the most interesting part is the third ‘light stage,’” says Milstein. “When we exposed this third complex to light at room temperature, not only was oxygen gas produced, but the metal complex also reverted back to its original state, which could be recycled for use in further reactions.”

These results are even more remarkable considering that the generation of a bond between two oxygen atoms promoted by a manmade metal complex is a very rare event, and it has been unclear how it can take place. Yet Milstein and his team have also succeeded in identifying an unprecedented mechanism for such a process. Additional experiments have indicated that during the third stage, light provides the energy required to cause the two OH groups to get together to form hydrogen peroxide (H₂O₂), which quickly breaks up into oxygen and water. “Because hydrogen peroxide is considered a relatively unstable molecule, scientists have always disregarded this step, deeming it implausible; but we have shown otherwise,” says Milstein. Moreover, the team has provided evidence showing that the bond between the two oxygen atoms is generated within a single molecule – not between oxygen atoms residing on separate molecules, as commonly believed – and it comes from a single metal center.

Discovery of an efficient artificial catalyst for the sunlight-driven splitting of water into oxygen and hydrogen is a major goal of renewable clean energy research. So far, Milstein’s team has demonstrated a mechanism for the formation of hydrogen and oxygen from water, without the need for sacrificial chemical agents, through individual steps, using light. For their next study, they plan to combine these stages to create an efficient catalytic system, bringing those in the field of alternative energy an important step closer to realizing this goal.

Participating in the research were former postdoctoral student Stephan Kohl, Ph.D. student Leonid Schwartsburd, and technician Yehoshoa Ben-David, all of the Organic Chemistry Department, together with staff scientists Lev Weiner, Leonid Konstantinovski, Linda Shimon, and Mark Iron of the Chemical Research Support Department.

Now, a unique approach developed by Prof. David Milstein and colleagues in the Weizmann Institute’s Organic Chemistry Department provides important steps in overcoming this challenge. The team has demonstrated a new mode of bond generation between oxygen atoms, and even defined the mechanism by which it takes place. In fact, it is the generation of oxygen gas by the formation of a bond between two oxygen atoms originating from water molecules that proves to be the bottleneck in the water splitting process. Their results have recently been published in Science.

Nature, by taking a different path, has evolved a very efficient process: photosynthesis – carried out by plants – the source of all oxygen on Earth. Although there has been significant progress towards the understanding of photosynthesis, just how this system functions remains unclear; vast worldwide efforts have been devoted to the development of artificial photosynthetic systems based on metal complexes that serve as catalysts, with little success. (A catalyst is a substance that is able to increase the rate of a chemical reaction without getting used up.)

The new approach devised by the Weizmann team is divided into a sequence of reactions, which leads to the liberation of hydrogen and oxygen in consecutive thermal- and light-driven steps, mediated by a unique ingredient – a special metal complex that Milstein’s team designed in previous studies. Moreover, the one that they designed – a metal complex of the element ruthenium is a “smart” complex in which the metal center and the organic part attached to it cooperate in the cleavage of the water molecule.

The team found that, upon mixing this complex with water, the bonds between the hydrogen and oxygen atoms break, with one hydrogen atom binding to its organic part, while the remaining hydrogen and oxygen atoms (OH group) bind to its metal center.

This modified version of the complex provides the basis for the next stage of the process: the “heat stage.” When the water solution is heated to 100˚C, hydrogen gas is released from the complex – a potential source of clean fuel – and another OH group is added to the metal center.

“But the most interesting part is the third ‘light stage,’” says Milstein. “When we exposed this third complex to light at room temperature, not only was oxygen gas produced, but the metal complex also reverted back to its original state, which could be recycled for use in further reactions.”

These results are even more remarkable considering that the generation of a bond between two oxygen atoms promoted by a manmade metal complex is a very rare event, and it has been unclear how it can take place. Yet Milstein and his team have also succeeded in identifying an unprecedented mechanism for such a process. Additional experiments have indicated that during the third stage, light provides the energy required to cause the two OH groups to get together to form hydrogen peroxide (H2O2), which quickly breaks up into oxygen and water. “Because hydrogen peroxide is considered a relatively unstable molecule, scientists have always disregarded this step, deeming it implausible; but we have shown otherwise,” says Milstein. Moreover, the team has provided evidence showing that the bond between the two oxygen atoms is generated within a single molecule – not between oxygen atoms residing on separate molecules, as commonly believed – and it comes from a single metal center.

Discovery of an efficient artificial catalyst for the sunlight-driven splitting of water into oxygen and hydrogen is a major goal of renewable clean energy research. So far, Milstein’s team has demonstrated a mechanism for the formation of hydrogen and oxygen from water, without the need for sacrificial chemical agents, through individual steps, using light. For their next study, they plan to combine these stages to create an efficient catalytic system, bringing those in the field of alternative energy an important step closer to realizing this goal.

Participating in the research were former postdoctoral student Stephan Kohl, Ph.D. student Leonid Schwartsburd, and technician Yehoshoa Ben-David, all of the Organic Chemistry Department, together with staff scientists Lev Weiner, Leonid Konstantinovski, Linda Shimon, and Mark Iron of the Chemical Research Support Department.

While exploding stars – supernovae – have been viewed with everything from the naked eye to high-tech research satellites, no one had directly observed what happens when a really huge star blows up. Dr. Avishay Gal-Yam of the Weizmann Institute’s Faculty of Physics and Prof. Douglas Leonard of San Diego State University recently located and calculated the mass of a gigantic star on the verge of exploding, following through with observations of the blast and its aftermath. Their findings have lent support to the reigning theory that stars ranging from tens to hundreds of times the mass of our sun all end up as black holes.

A star’s end is predetermined from birth by its size and by the “power plant” that keeps it shining during its lifetime. Stars, among them our sun, are fueled by hydrogen nuclei fusing together into helium in the intense heat and pressure of their inner cores. A helium nucleus is a bit lighter than the sum of the masses of the four hydrogen nuclei that went into making it and, from Einstein’s theory of relativity (E=MC²), we know that the missing mass is released as energy.

When stars like our sun finish off their hydrogen fuel, they burn out relatively quietly in a puff of expansion. But a star that’s eight or more times larger than the sun makes a much more dramatic exit. Nuclear fusion continues after the hydrogen is exhausted, producing heavier elements in the star’s different layers. When this process progresses to the point that the core of the star has turned to iron, another phenomenon takes over: In the enormous heat and pressure in the star’s center, the iron nuclei break apart into their component protons and neutrons. At some point, this causes the core and the layer above it to collapse inward, firing the rest of the star’s material rapidly out into space in a supernova flash.

A supernova releases more energy in a few days than our sun will release over its entire lifetime, and the explosion is so bright that one occurring hundreds of light years away can be seen from Earth even in the daytime. While a supernova’s outer layers are lighting up the universe with dazzling fireworks, the star’s core collapses further and further inward. The gravity created in this collapse becomes so strong that the protons and electrons are squeezed together to form neutrons, and the star’s core is reduced from a sphere 10,000 kilometers around to one with a circumference of a mere 10 kilometers. Just a crate-full of this star’s material weighs as much as our entire Earth. But when the exploding star is 20 times the mass of our sun or more, say the scientists, its gravitational pull becomes so powerful that even light waves are held in place. Such a star – a black hole – is invisible for all intents and purposes.

Until now, none of the supernovae stars that scientists had managed to measure had exceeded a mass of 20 suns. Gal-Yam and Leonard were looking at a specific region in space using the Keck Telescope on Mauna Kea in Hawaii and the Hubble Space Telescope. Identifying the about-to-explode star, they calculated its mass to be equal to 50-100 suns. Continued observation revealed that only a small part of the star’s mass was flung off in the explosion. Most of the material, says Gal-Yam, was drawn into the collapsing core as its gravitational pull mounted. Indeed, in subsequent telescope images of that section of the sky, the star seems to have disappeared. In other words, the star has now become a black hole – so dense that light can’t escape.

Dr. Avishay Gal-Yam’s research is supported by the Nella and Leon Benoziyo Center for Astrophysics; the Peter and Patricia Gruber Award; the Legacy Heritage Fund; and the William Z. and Eda Bess Novick Young Scientist Fund.

Even when our eyes are closed, the visual centers in our brain are humming with activity. Weizmann Institute scientists and others have shown in the last few years that the magnitude of sense-related activity in a brain that’s disengaged from seeing, touching, etc., is quite similar to that of one exposed to a stimulus. New research at the Institute has now revealed details of that activity, explaining why, even though our sense centers are working, we don’t experience sights or sounds when there’s nothing coming in through our sensory organs.

The previous studies of Prof. Rafael Malach and research student Yuval Nir of the Neurobiology Department used functional magnetic resonance imaging (fMRI) to measure brain activity in active and resting states. But fMRI is an indirect measurement of brain activity; it can’t catch the nuances of the pulses of electricity that characterize neuron activity.

Together with Prof. Itzhak Fried of the University of California at Los Angeles and a team at the EEG unit of the Tel Aviv Sourasky Medical Center, the researchers found a unique source of direct measurement of electrical activity in the brain: data collected from epilepsy patients who underwent extensive testing, including measurement of neuronal pulses in various parts of their brain, in the course of diagnosis and treatment.

An analysis of this data showed conclusively that electrical activity does indeed take place, even in the absence of stimuli. But the nature of the electrical activity differs if a person is experiencing a sensory event or undergoing its absence. In results that appeared recently in Nature Neuroscience, the scientists showed that during rest, brain activity consists of extremely slow fluctuations, as opposed to the short, quick bursts that typify a response associated with a sensory percept. This difference appears to be the reason we don’t experience hallucinations or hear voices that aren’t there during rest. The resting oscillations appear to be strongest when we sense nothing at all – during dream-free sleep.

The slow fluctuation pattern can be compared to a computer screensaver. Though its function is still unclear, the researchers have a number of hypotheses. One possibility is that neurons, like certain philosophers, must “think” in order to be. Survival, therefore, is dependant on a constant state of activity. Another suggestion is that the minimal level of activity enables a quick start when a stimulus eventually presents itself, something like a getaway car with the engine running. Nir: “In the old approach, the senses are ‘turned on’ by the switch of an outside stimulus. This is giving way to a new paradigm in which the brain is constantly active, and stimuli change and shape that activity.”

Malach: “The use of clinical data enabled us to solve a riddle of basic science in a way that would have been impossible with conventional methods. These findings could, in the future, become the basis of advanced diagnostic techniques.” Such techniques might not necessarily require the cooperation of the patient, allowing them to be used, for instance, on people in a coma or on young children.

For the scientific paper, please see: www.nature.com/neuro/journal/v11/n9/full/nn.2177.html

Bacteria are Models of Efficiency

The bacterium Escherichia coli, one of the best-studied single-celled organisms around, is a master of industrial efficiency. This bacterium can be thought of as a factory with just one product: itself. It exists to make copies of itself, and its business model is to make them at the lowest possible cost, with the greatest possible efficiency. Efficiency, in the case of a bacterium, can be defined by the energy and resources it uses to maintain its plant and produce new cells, versus the time it expends on the task.

Dr. Tsvi Tlusty and research student Arbel Tadmor of the Weizmann Institute of Science’s Physics of Complex Systems Department developed a mathematical model for evaluating the efficiency of these microscopic production plants. Their model, which appeared in the online journal PLoS Computational Biology, uses only five remarkably simple equations to check the efficiency of these complex factory systems.

The equations look at two components of the protein production process: ribosomes (the machinery in which proteins are produced) and RNA polymerase (an enzyme that copies the genetic code for protein production onto strands of messenger RNA for further translation into proteins). RNA polymerase is thus a sort of work “supervisor” that keeps protein production running smoothly, checks the specs, and sets the pace. The first equation assesses the production rate of the ribosomes themselves; the second, the protein output of the ribosomes; the third, the production of RNA polymerase. The last two equations deal with how the cell assigns the available ribosomes and polymerases to the various tasks of creating other proteins, more ribosomes, or more polymerases.

The theoretical model was tested in real bacteria. Do bacteria “weigh” the costs of constructing and maintaining their protein production machinery against the gains to be had from being able to produce more proteins in less time? What happens when a critical piece of equipment is in short supply – say, a main ribosome protein? Tlusty and Tadmor found that their model was able to accurately predict how an E. coli would change its production strategy to maximize efficiency following disruptions in the work flow caused by experimental changes to genes with important cellular functions.

What’s the optimum? The model predicts that a bacterium, for instance, should have seven genes for ribosome production. It turns out that that’s exactly the number an average E. coli cell has. Bacteria having five or nine get a much lower efficiency rating. Evolution, in other words, is a master efficiency expert for living factories, meeting any challenges that arise as production conditions change.

For the scientific paper, please see: www.ploscompbiol.org/article/info%3Adoi%2F10.1371%2Fjournal.pcbi.1000038

Weizmann Institute Scientists Show:

Extra Copies of a Gene Carry Extra Risk

Is more of a good thing better? A gene known as LIS1 is crucial for ensuring the proper placement of neurons in the developing brain. When an LIS1 gene is missing, brains fail to develop their characteristic folds; babies with lissencephaly, or “smooth brain,” are born severely mentally retarded. But new research by Prof. Orly Reiner of the Institute’s Molecular Genetics Department, which recently appeared in Nature Genetics, shows that having extra LIS1 genes can cause problems as well.

Reiner was the first to discover LIS1’s tie to lissencephaly, in 1993. Her latest study shows that LIS1 works by helping to determine polarity in the cell – how the various organelles are arranged inside the cell, as well as where it connects to neighboring cells. Neurons alter their polarity several times during development, especially when they take on an elongated shape and migrate to new locations in the brain.

But what if, rather than too little, the body has too much LIS1? One of the surprises to come out of the recent spate of post-human-genome research is the number of genes that can be repeated or deleted in an individual’s genome. Most extra copies of genes may be no more harmful than a computer backup disk, but scientists have been finding that some repeats can cause disease.

Research associate Dr. Tamar Sapir and lab technician Talia Levy, working in Reiner’s lab, developed a mouse model in which additional LIS1 protein was produced in the brain. The scientists found that the brains of these mice were a bit smaller than average. On closer inspection, they discovered a range of subtle changes in cell polarity and movement: nuclei within the proliferating zone tended to move faster, but with less control; rates of cell death were higher; and various factors in the cell became more disordered.

Reiner then asked whether their findings might apply to humans. Together with Jim Lupski and Drs. Weimin Bi and Oleg A. Shchelochkov of the Baylor College of Medicine in Houston, Texas, they searched through blood samples using a technique that matches a patient’s DNA with control DNA to identify additions or deletions in its sequence. They identified seven individuals with extra copies of either LIS1 or adjacent genes that are also involved in brain development. All suffered developmental abnormalities. Two of the patients – children with a second LIS1 gene – had previously been diagnosed with failure to thrive and delayed development, and were found to have small brain sizes. A third, who had three copies of the gene, was mentally retarded and suffered from bone deformation as well.

Reiner: “Several brain diseases, including schizophrenia, epilepsy, and autism, have been linked to faulty neuron migration, and recent research has hinted that some of these may involve variations in gene number. Our study is the first to demonstrate the effects of the duplication of a single gene in a mouse model and tie it to a new ‘copy number variation’ human disease.”

For the scientific paper, please see: www.nature.com/ng/journal/v41/n2/pdf/ng.302.pdf

Even when our eyes are closed, the visual centers in our brain are humming with activity. Weizmann Institute scientists and others have shown in the last few years that the magnitude of sense-related activity in a brain that’s disengaged from seeing, touching, etc., is quite similar to that of one exposed to a stimulus. New research at the Institute has now revealed details of that activity, explaining why, even though our sense centers are working, we don’t experience sights or sounds when there’s nothing coming in through our sensory organs.

The previous studies of Prof. Rafael Malach and research student Yuval Nir of the Neurobiology Department used functional magnetic resonance imaging (fMRI) to measure brain activity in active and resting states. But fMRI is an indirect measurement of brain activity; it can’t catch the nuances of the pulses of electricity that characterize neuron activity.

Together with Prof. Itzhak Fried of the University of California at Los Angeles and a team at the EEG unit of the Tel Aviv Sourasky Medical Center, the researchers found a unique source of direct measurement of electrical activity in the brain: data collected from epilepsy patients who underwent extensive testing, including measurement of neuronal pulses in various parts of their brain, in the course of diagnosis and treatment.

An analysis of this data showed conclusively that electrical activity does, indeed, take place even in the absence of stimuli. But the nature of the electrical activity differs if a person is experiencing a sensory event or undergoing its absence. In results that appeared recently in Nature Neuroscience, the scientists showed that during rest, brain activity consists of extremely slow fluctuations, as opposed to the short, quick bursts that typify a response associated with a sensory percept. This difference appears to be the reason we don’t experience hallucinations or hear voices that aren’t there during rest. The resting oscillations appear to be strongest when we sense nothing at all – during dream-free sleep.

The slow fluctuation pattern can be compared to a computer screen-saver. Though its function is still unclear, the researchers have a number of hypotheses. One possibility is that neurons, like certain philosophers, must ‘think’ in order to be. Survival, therefore, is dependant on a constant state of activity. Another suggestion is that the minimal level of activity enables a quick start when a stimulus eventually presents itself, something like a getaway car with the engine running. Nir: ‘In the old approach, the senses are ‘turned on’ by the switch of an outside stimulus. This is giving way to a new paradigm in which the brain is constantly active, and stimuli change and shape that activity.’

Malach: ‘The use of clinical data enabled us to solve a riddle of basic science in a way that would have been impossible with conventional methods. These findings could, in the future, become the basis of advanced diagnostic techniques.’ Such techniques might not necessarily require the cooperation of the patient, allowing them to be used, for instance on people in a coma or on young children.

For the scientific paper, please see:  http://www.nature.com/neuro/journal/v11/n9/full/nn.2177.html

In 2006, Prof. Nava Dekel of the Institute’s Biological Regulation Department, together with doctors in the in vitro fertilization (IVF) unit of the Kaplan Medical Center, made the surprising discovery that performing a uterine biopsy – causing a slight injury to the lining of the uterus just before a woman undergoes IVF doubles the chances of a successful pregnancy. Although the mechanism was not completely clear, Dekel and her team assumed that the injury provokes a response in the uterus that makes it more receptive to the embryo’s implantation.

The next year, Dekel was in Toronto, Canada, giving a lecture in the framework of the Weizmann Women and Science series, organized by Weizmann Canada. That lecture was reported in detail in a local Jewish newspaper, where it caught the attention of Howard and Roslyn Kaman. After many years of undergoing unsuccessful fertility treatments, failed IVF, and miscarriages, the article gave the couple new hope. They contacted Dekel by e-mail, and she referred them to Drs. Amichai Barash and Irit Granot, who had participated in the original research along with Drs. Yael Kalma and Yulia Gnainsky of the Weizmann Institute.

The doctors in Rehovot sent, as requested, a detailed description of the procedure, which was then performed in a fertility clinic in Toronto. The result: A healthy baby girl, Hannah Esther Angel Kaman, was born this past October.

Prof. Nava Dekel’s research is supported by the Kirk Center for Childhood Cancer and Immunological Disorders. Prof. Dekel is the incumbent of the Philip M. Klutznick Professorial Chair of Developmental Biology.

Weizmann Institute Scientists Create Working Artificial Nerve Networks
Scientists have already hooked brains directly to computers by means of metal electrodes, in the hope of both measuring what goes on inside the brain and eventually healing conditions such as blindness or epilepsy. In the future, the interface between brain and artificial system might be based on nerve cells grown for that purpose. In research that was recently featured on the cover of Nature Physics, Prof. Elisha Moses of the Physics of Complex Systems Department and his former research students Drs. Ofer Feinerman and Assaf Rotem have taken the first step in this direction by creating circuits and logic gates made of live nerves grown in the lab.

When neurons – brain nerve cells – are grown in culture, they don’t form complex “thinking” networks. Moses, Feinerman, and Rotem wondered whether the physical structure of the nerve network could be designed to be more brain-like. To simplify things, they grew a model nerve network in one dimension only – by getting the neurons to grow along a groove etched in a glass plate. The scientists found they could stimulate these nerve cells using a magnetic field (as opposed to other systems of lab-grown neurons that only react to electricity).

Experimenting further with the linear setup, the group found that varying the width of the neuron stripe affected how well it would send signals. Nerve cells in the brain are connected to great numbers of other cells through their axons (long, thin extensions), and they must receive a minimum number of incoming signals before they fire one off in response. The researchers identified a threshold thickness, one that allowed the development of around 100 axons. Below this number, the chance of a response was iffy, while just a few over this number greatly raised the chance a signal would be passed on.

The scientists then took two thin stripes of around 100 axons each and created a logic gate similar to one in an electronic computer. Both of these “wires” were connected to a small number of nerve cells. When the cells received a signal along just one of the “wires,” the outcome was uncertain; but a signal sent along both “wires” simultaneously was assured of a response. This type of structure is known as an AND gate. The next structure the team created was slightly more complex: Triangles fashioned from the neuron stripes were lined up in a row, point to rib, in a way that forced the axons to develop and send signals in one direction only. Several of these segmented shapes were then attached together in a loop to create a closed circuit. The regular relay of nerve signals around the circuit turned it into a sort of biological clock or pacemaker.

Moses: “We have been able to enforce simplicity on an inherently complicated system. Now we can ask, ‘What do nerve cells grown in culture require in order to be able to carry out complex calculations?’ As we find answers, we get closer to understanding the conditions needed for creating a synthetic, many-neuron ‘thinking’ apparatus.”

For the scientific paper, please see: www.nature.com/nphys/journal/v4/n12/pdf/nphys1099.pdf

Weizmann Institute Scientists Discover How Cancer Cells Survive a Chemotherapy Drug
What separates the few cancer cells that survive chemotherapy – leaving the door open to recurrence from those that don’t? Weizmann Institute scientists developed an original method for imaging and analyzing many thousands of living cells to reveal exactly how a chemotherapy drug affects each one.

For research student Ariel Cohen, together with Naama Geva-Zatorsky and Eran Eden in the lab of Prof. Uri Alon of the Institute’s Molecular Cell Biology Department, the question posed an interesting challenge. To approach it, they needed a method that would allow them to cast a wide net on the one hand – to sift through the numerous cellular proteins that could conceivably affect survival – but that would let them zoom in on the activities of individual cells in detail, on the other. Letting the computer take over the painstaking work of searching for anomalies enabled the team to look at the behavior of over 1,000 different proteins. Even so, it took several years to complete the project, which entailed tagging the specific proteins in each group of cancer cells with a fluorescent gene and capturing a series of time-lapse images over 72 hours. A second, fainter fluorescent marker was added to outline the cells so the computer could identify them. A chemotherapy drug was introduced 24 hours into this period, after which the cells began the process of either dying or defending themselves against the drug.

The team’s efforts have produced a comprehensive library of tagged cells, images, and data on cancer-cell proteins – a virtual goldmine of ready material for further cancer research. And they succeeded in pinpointing two proteins that seem to play a role in cancer cell survival.

Although most of the proteins behaved similarly in all the cells, the researchers found that a small subset of them – around five percent – could act unpredictably, even when the cells and drug exposure were identical. The scientists called these proteins bimodal, as they acted in one of two ways.

The team then asked whether any of the bimodal proteins they identified were those that occasionally promote cell survival. They found two molecules that seemed to fit the bill. One of them, known by the letters DDX5, is a multitasking protein that, among other things, plays a role in initiating the production of other proteins. The other, RFC1, also plays varied roles, including directing the repair of damaged DNA. When the researchers blocked the production of these proteins in the cancer cells, the drug became much more efficient at wiping out the growth.

Cohen: “This method gave us tremendous insight into how a cell responds to a drug. By conducting an unbiased study – we started with no preconceived notions of which proteins were involved – we were able to pinpoint possible new drug targets and to see how certain activities might boost the effectiveness of current drugs.”

For the scientific paper, please see: www.sciencemag.org/cgi/reprint/322/5907/1511.pdf

In addition, the Science Mobile, a teaching lab-in-a-van, is available to residents of the south free of charge. Its team can be invited to conduct entertaining and enjoyable science activities in southern Israel, in facilities protected from rocket attacks.

Click here to link to a brief video describing the Institute’s efforts to reach as many children as possible from the cities under attack, by bringing children to its Rehovot campus and also by dispatching a science mobile (a science lab in a van) to locations in the south where children are spending innumerable hours in bomb shelters.

Lee Brown brings to the position nearly three decades of experience in Chicago- and greater Midwest-area organizations focused on health, science, humanity, and personal development. As Vice President of Sinai Health System (encompassing Chicago’s Mt. Sinai Hospital, Schwab Rehabilitation Hospital, Mt. Sinai Children’s Hospital, Sinai Community Institute, and the Sinai Urban Health Institute), he was responsible for the structure and administration of the organization’s Department of Development, and also laid the groundwork for a $20 million capital campaign, its first in 20 years. Previously, Mr. Brown had been Director of Development for the Upper Midwest/Chicago Region of the Anti-Defamation League. He also worked for the American Cancer Society, The Salvation Army, and Boy Scouts of America.

In his role as Executive Director of the Midwest Region, Mr. Brown will advocate for the Weizmann Institute of Science and advance its mission of “Science for the Benefit of Humanity” in Chicago and the Midwestern United States. He will focus his efforts on enhancing and cultivating relationships with major donors in the area and recruiting new and diverse volunteer leadership in order to promote visibility of and support for the Weizmann Institute of Science.

Mr. Brown received his B.A. in Public Service from Northern Illinois University.

The program – entitled “Making Connections” – will bring together scientists from the Weizmann Institute of Science in Israel with their UK counterparts from the University of Oxford, the University of Cambridge, Imperial College London (ICL), and University College London (UCL).

The timing of the project’s launch is significant, as it comes amid continuing attempts to impose an academic boycott on Israeli institutions. The UK University and College Union (UCU) has just announced that it is ending its academic boycott of Israel.

Since its inception in 1950, this is the first time that Weizmann UK has provided grants for such an initiative, which is funded entirely by UK philanthropists.

As soon as the program was launched, it received 29 applications from the Weizmann Institute – far more than had been anticipated. Of these, 10 projects were shortlisted and, with the help of Professors Benjamin Chain (UCL), David Klug (ICL), and Haim Garty (Weizmann Institute), five were selected for funding by Weizmann UK.

The five winning research programs will focus on brain processes involved in learning and memory; understanding the nature of dark energy in the universe; the physical principles that govern the basic processes of living cells; deciphering the molecular events that take place in living cells; and the self-assembly of advanced materials.

Lord Mitchell, Chairman of Weizmann UK, said: “This is a very important development in international scientific collaboration. Our first five projects deal with some of the most challenging areas at the forefront of modern scientific investigation and we are proud to be leading the way.”

Weizmann Institute President Prof. Daniel Zajfman concurs: “Science knows no borders. Scientific ideas and discoveries, whether it be in the short- or long-term, benefit all humankind. Thus, it seems only natural that scientists worldwide should focus their efforts collectively in broadening the boundaries of human knowledge. Our vision is that this pioneering program will develop into a broad, prestigious, bi-national project, akin to existing programs that Israel has developed with the U.S. and Germany. It will be initiated on a competitive basis of quality assessment and will serve scientists from all universities and research institutions in the two countries.”

Originally planned as two programs over a five-year period, initial response suggests a swift increase may be possible.

The survey, published in The Scientist’s November issue, reviewed entries from over 2,300 qualified respondents. These respondents represented a total of 73 institutions: 54 from the U.S. and 19 from abroad. Survey respondents were asked to assess their work environments by indicating their level of agreement with 41 criteria, in eight different areas. Categories included the quality of mentoring, infrastructure and environment, pay, research resources, and tenure.

An analysis by the magazine determined that Australia is the best country overall in which to conduct scientific research. Runners-up were Israel, Belgium, the United States, and Canada. Readers ranked J. David Gladstone Institutes in San Francisco as the best academic environment in the United States.

Prof. Haim Garty, a Vice President of the Weizmann Institute, said in an interview with The Scientist, “What’s unique to us … is that the red tape is minimal. The Institute’s role is to provide the resources and stay out of the way.”

The Scientist, the magazine of life sciences, has been published for over 20 years. Details on the survey can be viewed at www.the-scientist.com.

Mindy Ginsberg brings to the position a strong background in fundraising and marketing in the Palm Beach area. She served as Director of Institutional Advancement, Southeast Region, for Yeshiva University and the Albert Einstein College of Medicine from November 2002 to May 2008. Previously, Ms. Ginsberg had served as an independent fundraising consultant for the National United Jewish Communities, as well as the Adolph and Rose Levis Jewish Community Center and the Mount Zion Foundation, both in Boca Raton. Ms. Ginsberg had also worked in senior development capacities for the Southeast Regional Office of National Hadassah (1996-9) and the Jewish Federation of Palm Beach County (1990-6).

In her role as Executive Director of the Palm Beach Region, Ms. Ginsberg will advocate for the Weizmann Institute of Science and advance its mission of Science for the Benefit of Humanity in southeastern Florida. In particular, she will focus her efforts on representing the Weizmann Institute to major donors in the area and recruiting new and diverse lay leadership. She succeeds Alex Bruner.

Ms. Ginsberg received her B.A. from Brandeis University. Her husband, David, owns DMG Insurance and Financial Services, and together they have two sons: Brandon, 12, and Steven, 9.

Rhoda and Gerald Blumberg first established their ties to the Weizmann Institute 35 years ago, and have been devoted supporters ever since. Their enthusiasm was passed down to their son, Larry, who is currently the American Committee’s Chairman and, like his father, worked his way through the ranks of leadership, serves in both legal and lay capacities. Larry is also an Institute Governor and the recipient of an honorary doctorate from the Institute. As experts in estate planning and charitable giving, Jerry and Larry have both lent their legal services to the American Committee. A former American Committee Vice President, today, at age 97, Jerry is an Honorary Vice Chairman and a Governor Emeritus of the Institute. Jerry, Rhoda, Larry, and Robin are all members of the President’s Circle and pillars of the Weizmann family.

President’s Circle members Joseph and Phyllis Gurwin have made philanthropy a priority, and Joseph’s children, Laura Flug and Eric Gurwin, have inherited this dedication to Weizmann. Laura is a member of the American Committee’s national Executive Committee and President’s Circle, following in the footsteps of her father, who is a Board member, Institute Governor, and recipient of an honorary doctorate from the Institute. Joseph’s wife, Phyllis, has recently been elected to the American Committee’s Board as well.

Presenting Sponsors Gladys and Morton Pickman have set an impressive example of generosity for the next generation, inspiring Gladys’s daughter and son-in-law, Ellen and Stephen Danetz, to become active supporters of the Weizmann Institute of Science. The philanthropic ethic cultivated by Gladys and Morton reflects the spirit of unity and history that characterize the Institute. Gladys and Ellen are descendants of one of the founding fathers of the Institute and the State of Israel, Harry Levine. Their close relationship with him inspired their fervent commitment to Israel and Weizmann, and Mac has led the way as a Board member, Institute Governor, and, along with Gladys, a member of the President’s Circle.

The benefit will also commemorate the 60th birthday of the State of Israel, as well as the 60th anniversary of the naming of the Weizmann Institute (founded 15 years earlier as the Daniel Sieff Research Institute). Political analyst Jeff Greenfield will act as the master of ceremonies, and the evening will feature entertainment by Miri Ben-Ari, known as the “Hip-Hop Violinist.”

All proceeds from the 2008 New York Gala will be applied to purchase a DNA Sequencing System–a critical piece of instrumentation required by Weizmann scientists working in a variety of research disciplines. The success of the Human Genome Project marked the beginning of a new era in genetics research, medical care, and technology: the era of individualized medicine. Thanks to advanced technology, the field of genomics is moving at an exponential rate, and reached another landmark in the fall of 2007 with the first-ever sequencing of the entire genome of an individual. Weizmann scientists include world-renowned genomics researchers, and the Institute was Israel’s liaison to the Human Genome Project. This prestige and brainpower must be fully utilized in order to keep up with the fast-moving science of the future, and to fulfill the Institute’s mission of “Science for the Benefit of Humanity.”

Today, the Weizmann Institute of Science in Rehovot, Israel, is one of the world's top-ranking multidisciplinary research institutions. Noted for its wide-ranging exploration of the natural and exact sciences, the Institute is home to 2,600 scientists, students, technicians, and supporting staff. Institute research efforts include the search for new ways of fighting disease and hunger, examining leading questions in mathematics and computer science, probing the physics of matter and the universe, creating novel materials, and developing new strategies for protecting the environment.

The Dinner Chairs are Gershon Kekst, Ellen Merlo, Andrew R. Morse, Bruce G. Pollack, and Larry Simon.

Airborne particles such as soot – known collectively as aerosols – rise into the atmosphere where they interact with clouds. Understanding what happens when the two meet is extremely complicated, in part because clouds are highly dynamic systems that both reflect the sun’s energy back into space, cooling the upper atmosphere, and trap heat underneath, warming the lower atmosphere and the Earth’s surface. Aerosols, in turn, can have both heating and cooling effects on clouds. On the one hand, water droplets form around the aerosol particles, which may extend the cloud cover. On the other hand, particles, especially soot, absorb the sun’s radiation, stabilizing the atmosphere and thus reducing cloud formation.

Dr. Ilan Koren and Hila Afargan of the Weizmann Institute’s Environmental Sciences and Energy Research Department, together with colleagues from UMBC and NASA’s Goddard Space Flight Center in Maryland, have, for the first time, developed an analytical model that puts all of these factors together to show when aerosols rising into the clouds will heat things up and when they will cool them off. The scientists tested their model on data from the Amazon, finding it reflected the true situation on the ground so accurately they could rule out the possibility that random changes in cloud cover – rather than aerosols from burning forests – were at work.

Their findings, which appear in the August 15, 2008 issue of Science, reveal that adding small quantities of aerosols into a clean environment can indeed produce a net cooling effect. As more and more particles enter the cloud layer, however, the effect progressively switches from cooling to heating mode. The researchers also found that the extent of the original cloud cover is important. A completely overcast sky prevents the sun’s rays from reaching the aerosols, so the result may be additional cooling of the atmosphere and the Earth’s surface. But the larger the ratio of open sky to clouds, the more aerosol particles absorb radiation, thus hastening the heating of the remaining cloud cover, reducing cloud cover, and heating the system.

An accurate model of the intricate relationship between clouds and aerosols has been a key missing piece in the picture of human-induced climate change. The scientists believe their findings may help both climate modelers and policy makers to understand the true climatic consequences of burning trees or sooty industrial fuels.

The quest to understand a cell’s path of descent, called a cell lineage tree, is shared by many branches of biology and medicine as gleaning such knowledge is key to answering many fundamental questions, such as whether neurons in our brain can regenerate, or whether new eggs are created in adult females.

So far, only tree lineages of tiny organisms, such as worms, which possess only a thousand cells, or “branches,” have been determined. Now, Prof. Ehud Shapiro of the Institute’s Biological Chemistry, and Computer Science and Applied Mathematics Departments, together with Doctoral students Dan Frumkin and Adam Wasserstrom have developed a novel way to reconstruct, in principle, trees for larger organisms, including humans.

The human body is made of about 100 trillion cells, all of which are descendants of a single cell – the fertilized egg (zygote). Cells that have undergone a small number of cell divisions are relatively close descendants (akin to branches representing children and grandchildren etc., on a family tree), while some cells may have undergone hundreds or even thousands of divisions (“distant cell generations”). Knowing the number of cell divisions since the zygote, known as the depth of cells, would enable scientists to address questions about the behavior of the body under physiological and pathological conditions.

Until now, estimates of cell depth were based on theoretical calculations and assumptions, but Shapiro provides a practical way of determining cell depth precisely. The concept behind their new method is simple: Previous research indicated that each time a cell divides, harmless mutations are introduced, and that “cell relatives” of distant generations tend to acquire more mutations, drifting away from the original DNA sequence of the zygote. Inspired by this, the team developed a non-invasive, accurate and systematic way, involving DNA amplification and computer simulations, to quantitatively estimate cell depth on the basis of the number of mutations in microsatellites (repetitive DNA sequences), and has applied it to several cell lineages in mice.

According to the team’s estimates, as reported in PLoS Computational Biology, the average depth of B cells – a type of immune cell – is related to mouse age, suggesting a rate of one cell division per day. In contrast, various types of adult stem cells underwent fewer divisions, supporting the notion that they are relatively quiescent.

Shapiro and Frumkin, in collaboration with Prof. Gideon Rechavi from the Sheba Medical Center and others then decided to apply this method to reconstruct, for the first time, the family tree of a cancer cell. “Despite several decades of scientific research, basic properties of the growth and spread of tumor cells remain controversial. This is surprising, since cancer is primarily a disturbance of cell growth and survival, and an aberrant growth pattern is perhaps the only property that is shared by all cancers. However, because the initiation and much of the subsequent development of tumors occurs prior to diagnosis, studying the growth and spread of tumors seems to require retrospective techniques and these have not been forthcoming,” explains Shapiro.

Therefore, by reconstructing a cancer cell lineage tree and performing an analysis of mutations accumulated in the cells, scientists would be able to trace back and reveal several aspects of the tumor’s developmental history. Shapiro: “We intend to apply this method to study key questions in human cancers, including when and where does a tumor initiate? The progression from pre-malignant to malignant states. At what stage does metastasis occur? Can the depth of tumor cells serve as a prognostic marker for cancer severity? And does chemotherapy target a subset of cells characterized by distinct lineage features (e.g. greater depth)?”

So far, their findings, featured on the cover of the July 15th issue of Cancer Research, show that cancer cells (extracted from tissue sections of a mouse lymphoma by laser micro-dissection) had almost double the number of branched generations (i.e., had divided almost twice as many times) compared to adjacent normal lung cells in the same amount of time. They were also able to calculate the age of the tumor and characterize its growth pattern. Further analysis was sufficient to corroborate the long-standing hypothesis on the single-cell origin of cancer.

The scientists believe cell lineage studies of cancer can greatly enhance our understanding of, and eventually lead us to the root of cancer.

But how does this happen? How exactly is the half embryo able to maintain its tissues and organs in the correct proportions despite being smaller than a normal sized embryo?

Despite many years of research, this question has remained unanswered – until now. More than 80 years since Spemann’s classic experiment, Profs. Naama Barkai, Benny Shilo and research student Danny Ben-Zvi of the Weizmann Institute of Science’s Molecular Genetics Department, together with Prof. Abraham Fainsod of the Hebrew University-Hadassah School of Medicine, Jerusalem, have finally discovered the mechanisms involved.

Previous studies have shown that the growth and development of cells and organs within the embryo is somehow linked to a special group of substances called morphogens. These morphogens are produced in one particular area within the embryo and then spread throughout the entire embryo in varying concentrations. Scientists then began to realize that the fate of embryo cells, that is to say, the type of tissue and organ they are eventually going to develop into, is determined by the concentration of morphogen that they come into contact with. But this information does not answer the specific question as to how proportion is maintained between organs?

The idea for the present research came about when Weizmann Institute scientist Prof. Naama Barkai and her colleagues developed a mathematical model to describe interactions that occur within genetic networks of an embryo.

The data ascertained from this model suggest that the way morphogens spread throughout the embryo in different concentrations is different than previously thought. The team predicts that an inhibitor molecule, which is secreted from a localized source at one side of the embryo and can bind the morphogen, acts as a type of ferry that "shuttles" the morphogen to the other side. Therefore, the mathematical model suggests that it is the interactions between the two substances that enable the embryo to keep the relative proportion between organs constant, irrespective of its size. Indeed, these predictions have been validated by experiments conducted on frog embryos by the research team.

The importance of the role of these morphogenic substances, as well as their mechanism of action, is evident by the fact that they have been conserved throughout evolution, where different variants can be found to exist in species ranging from worms to fruit flies and up to higher species including humans. Therefore, understanding the processes that govern embryonic cell development could have many implications. For example, it may lead, in the future, to scientists being able to repair injured tissues.

The Davidson Institute was founded in 2001 with a $20 million endowment gift from Guardian Industries Corp. Its establishment was a direct continuation and expansion of the activities of the Weizmann Institute in the field of science education. The Davidson Institute’s primary goal is to develop science, technology, and mathematics education in Israel. This most recent gift will strengthen its current positive impact, in addition to broadening its scope even further to include more children, teachers, and communities.

As the only institute of its kind – geared towards science education – the Davidson Institute is a prominent model throughout the world. It provides a wide range of educational programs and activities for teachers, students, and the general public. Its goal is to revitalize and nurture scientific, mathematical, and technological education both in the K-12 school system and the public at large. The Davidson Institute is active in the international arena in a number of areas of science education, including projects designated to promote development of leadership of science teachers, and joint science projects and activities between school classes from Israel and other countries.

In the interest of fostering high teaching standards, the Davidson Institute facilitates professional teacher development, organizing numerous long-term education programs, workshops, annual conferences, and seminars. The Davidson Institute also organizes unique activities to bring science closer to students of all ages and levels, from challenging the most advanced students, to providing tutoring and interactive support for those lagging behind. Finally, in the modern world, in which scientific and technological knowledge is essential to an individual’s performance, the Davidson Institute facilitates science literacy for the general public, initiating lectures, public discussions, and conferences on popular science.

“It is essential that the Weizmann Institute broaden its proven, successful educational science initiatives to reach even more people in Israel and around the world,” Mr. Davidson, President and C.E.O. of Guardian Industries Corp., said. “I believe that education – particularly science education – is an absolute necessity for a healthy and vibrant society.”

Prof. Haim Harari, who first initiated the Davidson Institute and has served as its Chairman since its founding, expressed his deep gratitude to the William Davidson Foundation and Mr. Davidson, stating that “in the 21st century, a certain level of understanding and appreciation of science and technology is a crucial component of any modern society, serving as the key to economic and intellectual success of every country and each individual. The numerous programs of the Davidson Institute of Science Education are dedicated to bringing science to all, whether they are exceptionally talented students, members of the general public, or youngsters who are outside the mainstream of society.”

Prof. Daniel Zajfman, President of the Weizmann Institute of Science, thanked Mr. Davidson on behalf of the William Davidson Foundation for its ongoing commitment and generosity. “Bill Davidson’s vision is that education is society’s most vital investment. We are honored that he has chosen to continue this successful partnership with the Weizmann Institute and carry out our mission of strengthening science education in Israel and beyond.”

Thermodynamics tell us that the interaction between a large heat source (a heat bath) and an ensemble of much smaller systems must bring them – at least on average – progressively closer to thermal equilibrium. Now Prof. Gershon Kurizki, Dr. Noam Erez and doctoral student Goren Gordon of the Chemical Physics Department, in collaboration with Dr. Mathias Nest of Potsdam University, Germany, have shown that ensembles of quantum systems in thermal contact with a heat bath could present a drastic departure from this allegedly universal trend, a prediction they recently reported in Nature.

With complete disregard for this physical rule, the ensemble may, remarkably, heat up even when it is hotter than the bath or cool down when it is colder. The scientists showed that if the energy of these systems is measured repeatedly, both systems and bath will undergo temperature increase or decrease, and this change depends only on the rate of measurement – not on the actual results of these measurements.

How can these effects of quantum measurements be explained? As opposed to classical measurement, which may be completely nonintrusive, measuring quantum systems decouples them from their heat bath. This decoupling, followed by recoupling of the two when measurement ceases, introduces energy (at the expense of the measuring apparatus) into the systems and the bath alike, and thus heats them up. When this happens over a very short time interval, the systems cannot be discriminated from the bath. For longer time intervals, the systems and bath start exchanging energy as coupled oscillators (analogous to connected springs). This energy exchange will cause the quantum systems to lose energy to the bath, thus lowering the temperature of the ensembles. Depending on whether the measurements are repeated at short or long intervals, it should be possible to heat up or cool down the systems.

The predicted effects may be the key to developing novel heating and cooling schemes for atomic, molecular and solid-state devices. Such schemes might allow ultrafast temperature control by optical measurements performed at an extremely high rate.

Weizmann Institute Scientists Find New “Quasiparticles”

Weizmann Institute physicists have demonstrated, for the first time, the existence of “quasiparticles” with one quarter the charge of an electron. This finding could be a first step toward creating exotic types of quantum computers that might be powerful, yet highly stable.

Fractional electron charges were first predicted over 20 years ago under conditions existing in the so-called quantum Hall effect, and were found by the Weizmann group some ten years ago. Although electrons are indivisible, if they are confined to a two-dimensional layer inside a semiconductor, chilled down to a fraction of a degree above absolute zero and exposed to a strong magnetic field that is perpendicular to the layer, they effectively behave as independent particles, called quasiparticles, with charges smaller than that of an electron. But until now, these charges had always been fractions with odd denominators: one third of an electron, one fifth, etc.

The experiment done by research student Merav Dolev in Prof. Moty Heiblum’s group, in collaboration with Drs. Vladimir Umansky and Diana Mahalu, and Prof. Ady Stern, all of the Condensed Matter Physics Department, owes the finding of quarter-charge quasiparticles to an extremely precise setup and unique material properties: The gallium arsenide material they produced for the semiconductor was some of the purest in the world. The scientists tuned the electron density in the two-dimensional layer – in which about three billion electrons were confined in the space of a square millimeter – such that there were five electrons for every two magnetic field fluxes. The device they created is shaped like a flattened hourglass, with a narrow “waist” in the middle that allows only a small number of charge-carrying particles to pass through at a time. The “shot noise” produced when some passed through and others bounced back caused fluctuations in the current that are proportional to the passing charges, thus allowing the scientists to accurately measure the quasiparticles’ charge.

Quarter-charge quasiparticles should act quite differently from odd fractionally charged particles, and this is why they have been sought as the basis of the theoretical “topographical quantum computer.” When particles such as electrons, photons, or even those with odd fractional charges change places with one another, there is little overall effect. In contrast, quarter-charge particle exchanges might weave a “braid” that preserves information on the particles’ history. To be useful for topologically-based quantum computers, the quarter-charge particles must be shown to have “non-Abelian” properties – that is the order of the braiding must be significant. These subtle properties are extremely difficult to observe. Heiblum and his team are now working on devising experimental setups to test for these properties.

Prof. Moty Heiblum’s research is supported by the Joseph H. and Belle R. Braun Center for Submicron Research. Prof. Heiblum is the incumbent of the Alex and Ida Sussman Professorial Chair in Submicron Electronics.

Weizmann Institute Scientists Develop A New Approach to Treating Autoimmune Disease
In autoimmune diseases, the immune system turns against the body’s own tissues and organs, wreaking havoc and destruction for no apparent reason. Partly because the origins of these diseases are so obscure, no effective treatment exists, and the suffering they inflict is enormous. Now Weizmann Institute scientists have developed a method that in the future may make it possible to treat autoimmune diseases effectively without necessarily knowing their exact cause. Their approach is equivalent to sending a police force to suppress a riot without seeking out the individuals who instigated the unrest.

In healthy people, a small but crucial group of immune cells called regulatory T cells, or T-regs, keeps autoimmunity in check, but in people with inflammatory bowel disease (IBD), one of the most common autoimmune disorders, too few of these cells appear in the diseased intestine, and the ones that do fail to function properly. The new Weizmann Institute approach consists of delivering highly selective, genetically engineered functioning T-regs to the intestine. The study was conducted by Dr. Eran Elinav, a physician from Tel Aviv Sourasky Medical Center’s gastroenterology institute who is working toward his Ph.D. at the Weizmann Institute, and lab assistant Tova Waks, in the laboratory of Prof. Zelig Eshhar of the Immunology Department.

Relying on Eshhar’s earlier work in which he equipped a different type of T cell to zero in on cancerous tumors, the team genetically engineered T-regs, outfitting these cells with a modular receptor consisting of three units. One of these units directed the cells to the intestine while the other two made sure they became duly activated. As reported in the journal Gastroenterology, the approach proved effective in laboratory mice with a disease that simulates human IBD: Most of the mice treated with the genetically-engineered T-regs developed only mild inflammation or no inflammation at all.

The cells produced what the scientists called a “bystander” effect: They were directed to the diseased tissue using neighboring, or “bystander” markers that identified the area as a site of inflammation, and suppressed the inflammatory cells in the vicinity by secreting soluble suppressive substances.

The scientists are currently experimenting with human T-regs for curing ulcerative colitis and believe that in addition to IBD, their “bystander” approach could work in other autoimmune disorders, even if their causes remain unknown. They also think the method could be valuable in suppressing unwanted inflammation in diseases unrelated to autoimmunity, as well as in preventing graft rejection and certain complications in bone marrow and organ transplantation, in which inflammation is believed to play a major role.

Living cells become infected by viruses in two steps. First, the virus penetrates the cell. Next, in the second and crucial step, the cell starts producing new viruses, which spread and infect additional cells. At the beginning of this production process, the cell makes the outer wall of the virus, which is a container of sorts composed of proteins and known as the capsid. The cell then makes copies of viral DNA and inserts it into the capsid. The result is a new, functioning virus that is ready to leave the host cell and infect more cells.

Understanding how viruses infect cells and how new viruses are produced in the course of the infection allows scientists to interrupt the infection cycle, blocking viral diseases. One of the difficulties, however, is that the invasion strategies of different viruses greatly vary from one another.

The mimivirus, known, among other things, for its exceptional size – it is five to ten times larger than any other known virus – poses an interesting challenge in this respect. This virus was discovered only in the late twentieth century, as its extraordinary size made it impossible to identify it by regular means. In addition, it contains much more genetic material than other viruses, a feature that forces the mimivirus to develop particularly efficient methods for introducing its viral DNA into the host cell and for inserting the genetic “parcel” into the protein container during the production of new viruses in the host cell.

The Weizmann Institute’s Prof. Abraham Minsky and graduate students Nathan Zauberman and Yael Mutsafi of the Organic Chemistry Department, together with Drs. Eugenia Klein and Eyal Shimoni of Chemical Research Support, have now revealed the details of some of the methods used by this virus. In their new study, the scientists have obtained, for the first time, three-dimensional pictures of the openings through which the viral genetic material is injected into an infected cell, and of the process by which this genetic material is inserted into the protein capsid.

In all previously studied viruses, viral genetic material was shown to be injected into the cell (during the cell’s infection) and to enter the newly formed protein container (during the production of new viruses inside the cell) through the same channel, which was created in the viral container. In contrast, the Institute scientists discovered that the giant mimivirus uses a different channel – located in a different part of its capsid – for each of these two goals. The scientists also discovered that the DNA helix in both these processes does not form a long thread, as in other viruses, but rather is organized into a densely packed block. The researchers believe that these unique traits serve to specifically facilitate both the injection into the host cell and the insertion of the large quantity of genetic material in the mimivirus.

In the Weizmann study, electron microscope images of the mimivirus invading an amoeba cell showed that just after invasion, the walls of the protein capsid – a polygon composed of 20 triangles – separate from one another and open up like flower petals to create a large, star-shaped entry nicknamed the “stargate.” The viral membrane underneath the stargate fuses with the amoeba cell membrane, creating a broad channel that leads into the amoeba. The pressure released with the sudden opening of the walls – which is 20 times greater than the pressure pushing the cork out of a Champagne bottle – pushes the viral DNA into the channel, whose large dimensions allow the genetic material to pass quickly into the amoeba cell.

Additional images show how the viral genetic material is inserted into the newly formed protein container when new viruses are produced in the host cell. In this process, the viral genetic material is delivered to its destination through an opening in the new container’s wall opposite the stargate. The insertion must overcome the pressure inside the container and is probably driven by an “engine” located within the wall that harbors the opening.

The scientists believe that the study of the mimivirus’s life cycle, from cellular infection to the production of new viruses, may yield valuable insights into the mechanisms of action of numerous other viruses, including those that cause human diseases.

We know the musical note do is farther from la than from re on a scale – not only because our ears tell us the distance is greater, but because their frequencies are farther apart. No such physical relationship had been discovered for smells, in part because odor molecules are much more difficult to pin down than sound frequencies. To create their map, the scientists began with 250 odorants and generated, for each, a list of around 1,600 chemical characteristics. From this dataset, the researchers, led by Rafi Haddad, a graduate student with Prof. Noam Sobel in the Neurobiology Department, and Prof. David Harel of the Computer Science and Applied Mathematics Department, together with their colleague Rehan Khan, created a multidimensional map of smells that revealed the distance between one odor molecule and another.

Eventually, they pared the list of traits needed to situate an odor on the map down to around 40. They then checked to see whether the brain recognizes this map, similar to the way it recognizes musical scales. They reexamined numerous previously published studies that measured the neural response patterns to smells in a variety of lab animals – from fruit flies to rats – and found that across all the species, the closer any two smells were on the map, the more similar the neural patterns. The scientists also tested 70 new odors by predicting the neural patterns they would arouse and running comparisons with the unpublished results of olfaction experiments done at the University of Tokyo. They found that their predictions closely matched the experimental results.

These findings lend support to the scientists’ theory that, contrary to the commonly held view that smell is a subjective experience, there are universal laws governing the organization of smells, and these laws determine how our brains perceive them.

Weizmann Institute Scientists Build a Better DNA Molecule
Building faultless objects from faulty components may seem like alchemy. Yet scientists from the Weizmann Institute’s Computer Science and Applied Mathematics and Department of Biological Chemistry have achieved just that, using a mathematical concept called recursion. “We all use recursion, intuitively, to compose and comprehend sentences like ‘the dog that chases the cat that bit the mouse that ate the cheese that the man dropped is black,’” says Prof. Ehud Shapiro.

Recursion allows long DNA molecules to be composed hierarchically from smaller building blocks. But synthetic DNA building blocks have random errors within their sequence, as do the resulting molecules. Correcting these errors is necessary for the molecules to be useful. Even though the synthetic molecules are error prone, some of them are likely to have long stretches that do not contain any faults. These stretches of faultless DNA can be identified, extracted, and reused in another round of recursive construction. Starting from longer and more accurate building blocks in this round increases the chances of producing a flawless long DNA molecule. The team, led by doctoral students Gregory Linshiz and Tuval Ben-Yehezkel under the supervision of Shapiro, found in their experiments that two rounds of recursive construction were enough to produce a flawless target DNA molecule. If need be, however, the error correction procedure could be repeated until the desired molecule is formed.

The team’s research, recently published in the journal Molecular Systems Biology, provides a novel way to construct faultless DNA molecules with greater speed, precision, and ease of combining synthetic and natural DNA fragments than existing methods. “Synthetic DNA molecules are widely needed in biological and biomedical research, and we hope that their efficient and accurate construction using this recursive process will help to speed up progress in these fields,” says Shapiro.

Prof. Ehud Shapiro’s research is supported by the Clore Center for Biological Physics; the Arie and Ida Crown Memorial Charitable Fund; the Cymerman - Jakubskind Prize; the Fusfeld Research Fund; the Phyllis and Joseph Gurwin Fund for Scientific Advancement; the Henry Gutwirth Fund for Research; Ms. Sally Leafman Appelbaum, Scottsdale, AZ; the Carolito Stiftung, Switzerland; the Louis Chor Memorial Trust Fund; and the estate of Fannie Sherr, New York, NY. Prof. Shapiro is the incumbent of the Harry Weinrebe Chair of Computer Science and Biology.

Weizmann Institute Scientists Create New Nanotube Structures
Thanks to the rising trend toward miniaturization, carbon nanotubes – which are about 100,000 times thinner than a human hair and possess several unique and very useful properties – have become the choice candidates for use as building blocks in nanosized electronic and mechanical devices. But it is precisely their infinitesimal dimensions, as well as their tendency to clump together, that make it difficult for scientists to manipulate nanotubes.

Dr. Ernesto Joselevich, together with Ph.D. student Ariel Ismach and former M.Sc. student Noam Geblinger of the Weizmann Institute’s Materials and Interfaces Department, are developing techniques to coax carbon nanotubes to self-assemble into ordered structures – essentially making the nanotubes do the hard work for them.

Ironically, the universal principle of “order through chaos” has allowed the team’s most recent research to give rise to nanotubes that are strikingly more ordered and complex than any ever observed before. These intriguing new nanotube structures, which the scientists have dubbed “serpentines” due to their self-assembly into snake-like or looped configurations, have recently been reported in the cover article of the journal Nature Nanotechnology.

“It may seem paradoxical – trying to create order through chaos – but in fact, this is a common phenomenon on the macroscale. Systems affected by forces that fluctuate from one extreme to another tend to self-organize into much more complexly ordered structures than those in which the external forces are ‘calm.’ We applied this principle at the nanoscale to see if it would have the same effect, and indeed, it did,” says Joselevich.

Serpentines are a common geometry in many functional macroscale systems: antennas, radiators, and cooling elements. Analogously, nanotube serpentines could find a wide range of nano-device applications, such as cooling elements for electronic circuits and opto-electronic devices, as well as in power-generating, single-molecule dynamos. “But the feature I find most intriguing about these serpentines,” says Joselevich, “is their beauty.”

A typical supernova is preceded by the burn-out of a massive star. When the nuclear fuel at its core runs out, the star collapses under its own weight. The resulting body, now known as a neutron star, is so dense that one teaspoonful of its core material weighs as much as all the humans on earth. This extreme compression is followed by a rebound, creating a shock wave that bounces off the surface of the newly-formed neutron star and rips through its outer, gaseous layers. These layers are ejected, flying off the surface in rapidly expanding shells.

For the last four decades, astronomers have theorized that the explosion is preceded by a burst of x-ray radiation that lasts for several minutes. For the first time, that burst was actually seen all previous observations had taken place when the star was already an expanding shell of debris, days or even weeks after the explosions’ start. Both luck and the Swift satellite’s unique design played a role in the discovery. In January of this year, Drs. Alicia Soderberg and Edo Berger of Princeton University, USA, were using the satellite, which measures gamma rays, X rays and ultraviolet light, to observe another supernova in a spiral galaxy in the Lynx constellation, 90 million light-years from Earth. At 9:33 EST, they spotted an extremely bright five-minute X-ray burst and realized it was coming from another location within the same galaxy.

The Princeton scientists immediately assembled a team of 15 research groups around the world to investigate, including Prof. Eli Waxman and Dr. Avishay Gal-Yam of the Weizmann Institute’s Physics Faculty. Gal-Yam performed measurements and calculations that enabled the scientific team to cancel out the various disturbances that affect astronomical data, such as radiation-absorbing interstellar dust, which skews observed measurements. The shock-wave eruption and X-ray generation of this supernova explosion went exactly according to the theoretical model that Waxman and Prof. Peter Meszaros of Penn State University had developed earlier. The data showed that the explosion – known as supernova 2008D – is a relatively common type of supernova, and not a rare supernova involving jets of gamma ray radiation.

Already, the observation has provided scientists with valuable new information on supernovae, including the dimensions of the exploding star, the structure of its envelope and the properties of the shock wave that hurls off the star’s outer envelope. As they continue to analyze the data, the scientists believe it may help them to solve some of the outstanding puzzles surrounding these types of explosion. For instance, according to mathematical calculations of the forces involved in neutron star collapse, the bouncing shock wave should stall out before it manages to eject the stellar envelope. Clearly, this is not what happens in nature, but clues found in the Swift observations may help researchers to correct the model.

Now that they have observed a supernova from the pre-explosion stage, the scientists are not only gaining a better understanding of the little-understood processes that make these stars explode, they hope their knowledge of the x-ray emissions will enable them to catch more stars that are right on the brink of becoming supernovae.

Studies will take place two days a week for the first two years, and one day a week in the third year. The rest of the week, the participants can continue their normal teaching duties. Participants will be selected on the basis of recommendations and personal interviews, and each will receive a study grant in addition to an exemption from tuition.

For teachers who already have advanced degrees, the program offers a multi-track option that will integrate practical studies with research that will take place one day a week. Participants in this branch of the program are also eligible for study scholarships.

A continuing-education program will be offered to those who finish either track, in collaboration with the Science Teaching Department and other scientific departments at the Weizmann Institute, and with the Davidson Institute of Science Education, which also conducts its activities at the Weizmann Institute. The continuing-education program will aim to support the participants in developing and implementing innovative science education projects.

The Caesarea Program is open to outstanding science and math teachers who have at least three years of teaching experience. Those teachers chosen to participate in this prestigious program are required to commit to teaching for at least another three years after they complete their studies.

Enzymes are, without a doubt, a valuable model for understanding the intricate works of nature. These molecular machines – which life would not exist without – are responsible for initiating chemical reactions within the body. Millions of years of natural selection have fine-tuned the activity of such enzymes, allowing chemical reactions to take place millions of times faster. In order to create artificial enzymes, a comprehensive understanding of the structure of natural enzymes and their mode of action, as well as advanced protein engineering techniques, is needed. A team of scientists from the University of Washington, Seattle, and the Weizmann Institute of Science, Israel, have made a crucial breakthrough toward this endeavor. Their findings have recently been published in the scientific journal Nature.

Enzymes are biological catalysts that are made from a string of amino acids, which fold into specific three-dimensional protein structures. The scientists’ aim was to create an enzyme for a specific chemical reaction whereby a proton (a positively charged hydrogen atom) is removed from carbon – a highly demanding reaction and rate-determining step in numerous processes for which no enzymes currently exist, but which would be beneficial in helping to speed up the reaction. During the first heat of the “competition,” the research team designed the “heart” of the enzymatic machine – the active site – where the chemical reactions take place.

The second heat of the competition was to design the backbone of the enzyme; i.e., to determine the sequence of the 200 amino acids that make up the structure of the protein. This was no easy feat, seeing as there are an infinite number of ways to arrange 20 different types of amino acids into strings of 200. But in practice, only a limited number of possibilities are available, as the sequence of amino acids determines the structure of the enzyme which, in turn, determines its specific activity. Prof. David Baker of the University of Washington, Seattle, used novel computational methodologies to scan tens of thousands of sequence possibilities, identifying about 60 computationally designed enzymes that had the potential to carry out the intended activity. Of the 60 tested sequences, eight advanced to the next “round,” having showed biological activity. Of these remaining eight, three sequences got to the “final stage,” which proved to be the most active. Drs. Orly Dym and Shira Albeck of the Weizmann Institute’s Structural Biology Department solved the structure of one of the final contestants, and confirmed that the enzymes created were almost identical to the predicted computational design.

But the efficiency of the new enzymes could not compare to that of naturally occurring enzymes that have evolved over millions of years. This is where “mankind” was on the verge of losing the competition to nature, until Prof. Dan Tawfik and research student Olga Khersonsky of the Weizmann Institute’s Biological Chemistry Department stepped in and were able to develop a method allowing the synthetic enzymes to undergo “evolution in a test tube” that mimics natural evolution. Their method is based on repeated rounds of random mutations, followed by scanning the mutant enzymes to find the ones that showed the most improvement in efficiency. These enzymes then underwent further rounds of mutation and screening. Results show that it takes only seven rounds of evolution in a test tube to improve the enzymes’ efficiency 200-fold, compared with the efficiency of the computer-designed template, resulting in a million-fold increase in reaction rates compared with those that take place in the absence of an enzyme.

The scientists found that the mutations occurring in the area surrounding the enzyme’s active site caused minor structural changes, which in turn resulted in an increased chemical reaction rate. These mutations, therefore, seem to correct shortcomings in the computational design by shedding light on what might be lacking in the original designs. Other mutations increased the flexibility of the enzymes, which helped to increase the speed of substrate release from the active site.

“Reproducing the breathtaking performances of natural enzymes is a daunting task, but the combination of computational design and molecular in vitro evolution opens up new horizons in the creation of synthetic enzymes,” says Tawfik. “Thanks to this research, we have gained a better understanding of the structure of enzymes, as well as their mode of action. This, in turn, will allow us to design and create enzymes that nature itself had not ‘thought’ of, which could be used in various processes, such as neutralizing poisons and developing medicines, as well as for many further potential applications.”

Mr. Levin, former Senior Associate National Director and Director of National Development for the Anti-Defamation League (ADL), was selected after a nationwide search for a candidate to direct the American Committee. The Committee represents the Weizmann Institute of Science, based in Rehovot, Israel, and develops philanthropic support in the U.S. for the Institute’s scientific research programs.

Lawrence S. Blumberg, Chairman of the American Committee’s Board of Directors, announced Mr. Levin’s appointment. A search committee presented its findings to the Board’s Executive Committee, which approved the selection of Mr. Levin.

“We are delighted and fortunate that Marshall Levin is joining the American Committee at this time in our organization’s history,” Mr. Blumberg said in New York. “He brings an exceptional portfolio of relevant professional experience to the Weizmann Institute family, including managing major national fund-raising programs; broad knowledge of and a substantial connection to Israel; private sector entrepreneurial expertise; and most importantly, a true passion for our mission of Science for the Benefit of Humanity.” Marshall Levin’s professional reputation spans the globe and includes senior positions in Jewish communal life and in the private sector. Mr. Levin is an honors graduate of Swarthmore College. He holds a Master of Social Service from Bryn Mawr Graduate School of Social Work and Social Research. In addition to his senior position at ADL, Mr. Levin served as Executive Director of Financial Resource Development for UJA-Federation of New York; Executive Director of Community Planning & Allocations for The Associated:Jewish Community Federation of Baltimore; Supervisor of Northern Israel in charge of Crisis Intervention for the Ministry of Social Welfare; Lecturer at the Haifa University School of Social Work; and executive director of synagogues in the Conservative and Reform movements.

In the for-profit arena, Mr. Levin served as president and CEO of a national education and entertainment company, and as editor-in-chief of a publishing house.

At the American Committee, Mr. Levin will direct and oversee the organization’s extensive financial resource development activities in the U.S., including its 10 regional offices. During the 2007 fiscal year, the Committee raised $121 million for the Weizmann Institute, exceeding the previous year’s $89 million achievement.

“It is a privilege to work on behalf of an institution that serves all of humanity without distinction and has improved the quality of lives of millions of people around the globe,” Mr. Levin said. “Moreover, it is a privilege to represent one of Israel’s finest assets, and to know that our efforts here will directly assist the Weizmann Institute to maintain and expands its record of excellence in scientific research and education.”

Mr. Levin succeeds Martin Kraar in the position, who recently concluded a decade of service at the American Committee.

Based on principles of active sensing that are widely adopted in the animal kingdom, the multinational team is developing innovative touch technologies, including a “whiskered” robotic rat. The whiskered robot will be able to quickly locate, identify, and capture moving objects. “The use of touch in the design of artificial intelligence systems has been largely overlooked, until now,” says Prof. Ehud Ahissar of the Weizmann Institute of Science’s Neurobiology Department, whose research team is one of the groups participating in the multinational project.

“In nocturnal creatures, or those that inhabit poorly lit places, the use of touch is widely preferred to vision as a primary means of learning and receiving physical information about their surrounding environment.” One such animal that employs this method is the rat. Several groups of the international consortium are investigating the ways in which rats use their bristly whiskers to explore their environment, and how their brains process such information. “If we succeed in understanding what makes an animal’s sense of touch so efficient, we will be able to develop robots imitating this feature, and put them to effective use.”

What is the whisker’s “secret”? Why is the sense of touch through a rat’s whiskers much more efficient than that of the average person’s fingertips? The consortium’s teams have provided some insights into these questions. One explanation concerns the way in which the sensory system works: Whiskers actively sweep back and forth repetitively, accumulating information about the surrounding environment. The sensing begins in the neurons at the whiskers’ bases, which then fire signals off to the brain. Moreover, experiments have shown that the way in which a rat uses its whiskers is context-dependent. The seemingly simple act of feeling out a three-dimensional object, for example, requires three different types of code, each encoding a different dimension — the horizontal, the vertical, and the radial (distance from the whisker base). The horizontal plane, for instance, is encoded in the precise timing of neural signals relative to the whisking motion. The vertical, i.e., the object height, is encoded by the vertical spacing of the whiskers, which are arranged grid-like on either side of the snout. The radial plane, on the other hand, is encoded in the number of times the neurons fire: The closer an object is to the rat’s snout, the higher the number of neuron-signaling spikes.

The consortium’s research also suggest that the signals travel from the whiskers through parallel pathways that function within parallel closed feedback loops, constantly monitoring the signals they receive and changing their responses accordingly. The researchers believe that it is the complex interactions between the feedback loops that are responsible for the rich and accurate control of movement, but at the same time, it poses an engineering challenge when trying to build artificial systems based on this concept.

“In order to investigate the role of feedback loops further,” says Prof. David Golomb of Ben Gurion University, Israel, whose research team is one of the groups participating in the multinational project, “consortium members will implement theoretical methods and calculations from theoretical physics and applied mathematics in order to develop and research models that describe the complicated neural processes that control active sensing.” The models are based on experimental observations, and are expected to be tested by experimental consortium teams.

Ahissar: “The aim of this research is to help gain a better understanding of the brain, on the one hand, and to advance technology on the other. That is to say, researchers can use robots as an experimental tool, by building a brain-like system, step-by-step, gaining insights into the workings of the brain’s inside components. With regard to technological applications, we suggest that it is the multiple closed feedback loops that are the key features giving biological systems an advantage over robotic systems. Therefore, implementing this biological knowledge will hopefully allow robotics researchers to build machines that are more efficient, which can be used in rescue missions, as well as search missions under conditions of restricted visibility.”

The BIOTACT project, which is funded primarily by the EC Seventh Research Framework Programme, includes participation by scientists from universities, research institutes, and high-tech companies from Britain, Israel, Switzerland, Italy, France, Germany, and the U.S.

The Scholarship Fund was established by the Perlman Family Foundation. This contribution makes a significant impact upon the Weizmann Institute’s world-renowned cancer research programs. The Perlman family’s generosity will now make $1,250,000 available for cancer research at the Weizmann Institute’s campus in Rehovot, Israel, where scientists are gaining new insights into how cancer develops and spreads, in addition to developing better treatments, preventions, and diagnostics.

Joan “Joni” Perlman Rosenberg was the youngest child of Jane and the late Harold L. Perlman, who were treasured friends of the Weizmann Institute and members of the American Committee’s President’s Circle. Harold Perlman was a long-standing member of its International Board of Governors and was the founding Chairman of the Chicago Region of the American Committee for the Weizmann Institute of Science. Harold and Jane Perlman’s most prominent gift was the establishment of the Perlman Chemical Sciences Building, home of the Departments of Materials and Interfaces and Chemical Physics, and the focal point of research in these disciplines since its dedication more than three decades ago. The Perlmans also founded the Perlman Institute of Chemical Sciences, the Perlman Wing for Magnetic Resonance Spectroscopy, and took part promoting scholarly exchanges between Institute scientists and their counterparts in American centers of research and higher education. Harold was awarded the title of Weizmann Honorary Fellow in 1974.

Joni Perlman was an educator in the Chicago area, where she was born and raised. She and her husband, Laurence “Larry” M. Rosenberg, had three sons: David, Daniel, and Michael. After receiving her Master’s degree in Education, she became a school teacher until dedicating herself full-time to the care of her family and raising of her boys. Her teaching career was to be the beginning of her lifelong work for the welfare of children, and she remained active until the very end of her life volunteering in the Jewish community for children’s causes.

In 1984, she died of breast cancer at age 45. The Scholarship Fund established in her name at the Weizmann Institute of Science honors her commitment to education by encouraging the pursuit of knowledge. It is also faithful to her mantra — “Live, Love, Laugh” —as it aspires to a brighter future and an enhanced quality of life for others with cancer.

The Joni Perlman Rosenberg Scholarship Fund for the Support of Cancer Research continues the Perlman family’s philanthropic tradition with the Weizmann Institute of Science. The Scholarship will be used to support students at the Weizmann Institute’s Feinberg Graduate School participating in cancer research.

The funds will be used by the Weizmann Institute of Science in Israel for two major initiatives: the Lorry I. Lokey Pre-Clinical Research Facility and the Lorry I. Lokey Research School of Biochemical Sciences. The gift is the largest single contribution ever made to the American Committee in its 63-year history.

Lokey is the founder of Business Wire, a leading San Francisco-based news release distribution service. During a recent visit to the campus of the Weizmann Institute, he called the philanthropic gift “one of the best investments of my life.”

As the only facility of its kind in Israel and in the region, the Pre-Clinical Research Facility will dramatically increase the resources of Weizmann Institute scientists, particularly in research areas with medical and health implications. When completed, it will be the largest core research facility on the Institute’s campus.

The facility will be utilized by many of the Institute’s 130 biological science research groups, and will house the campus’s most advanced imaging equipment. Research conducted in the building will span the medical spectrum, including studies on cancer, genetic disorders, neurodegenerative diseases, diabetes, bone and muscle development, and immune system disorders.

Thanks to a dedicated suite of biohazard laboratories, scientists also will be able to research viruses and lower-grade infectious diseases, such as influenza and hepatitis.

The Weizmann Institute’s biochemistry graduates already play leadership roles internationally and in Israel’s academic and private sectors in biotechnology, hi-tech, security, pharmaceuticals, and other key drivers of the Israeli economy. The new Lorry I. Lokey Research School of Biochemical Sciences will be a centerpiece of the Institute’s graduate education program. By boosting student benefits and the school’s visibility, Lokey’s endowment will make the school even more competitive, and help ensure that it will be among the top choices for talented graduate students worldwide in the life sciences.

Each new Ph.D. student in the Lokey Research School will be supported directly by an increased budget (supplementing the scholarship all Graduate School students currently receive, which covers the cost of tuition and a living stipend). Other new planned amenities include a prestigious annual colloquium which would bring top life scientists to the Weizmann Institute campus.

Professor Daniel Zajfman, President of the Weizmann Institute, said that Lokey’s gift will have a profound effect on the future of science, Israel, and every graduate bearing the Lokey Research School name with pride.

“Lorry Lokey understands that the partnership between science and philanthropy has the potential to improve dramatically the quality of our lives and to reduce human suffering. We are so grateful for his visionary leadership and for the trust he places in the scientists and students of our Institute,” he said.

Richard H. Jones, U.S. Ambassador to Israel, said that Lokey’s gift “helps strengthen the ties between Israel and the U.S.,” in addition to furthering science research that serves all of humanity without distinction.

As one of the nation’s leading philanthropists, Lokey’s many other charitable activities emphasize both science research and education, particularly in universities and high schools.

The benefit will honor Michael Lewitt, President and Managing Member of Hegemony Capital Management, LLC, a boutique investment advisory firm which he co-founded. The dinner will celebrate Mr. Lewitt’s individual accomplishments, as well as the innovative spirit the Weizmann Institute of Science brings to the Palm Beach community.

Dinner Co-Chairs are Cindy and Dr. Jeffrey Braun, Suzy Garfinkle, Karen Stein, and Rick Stone. Dr. Harlan Waksal, a member of the American Committee’s Executive Committee and President’s Circle and Secretary of the Board of Directors, will serve as master of ceremonies. Dr. Waksal will highlight some of the most recent breakthroughs at the Institute, and will discuss Weizmann’s philosophy of multidisciplinary, collaborative, curiosity-driven basic science research.

Pulitzer Prize-winning columnist George Will, whose column for The Washington Post is syndicated in almost 500 newspapers in the United States and Europe, will be the keynote speaker. Mr. Will is a contributing editor of Newsweek magazine, a founding panelist on ABC television’s This Week, and an author of several books about political theory and baseball.

As the evening’s honoree, Mr. Lewitt will receive the first Dr. Albert Willner Leadership Award. Named for Dr. Albert Willner, President Emeritus of the American Committee, the award honors outstanding individuals for their critical contributions to the community on behalf of the Weizmann Institute of Science.

The Weizmann Institute of Science, located in Rehovot, Israel, is one of the world’s leading centers of science and technology research. The Institute’s 2,600-strong scientific community addresses crucial problems in health and medicine, energy, technology, agriculture, and the environment. The Institute also plays a key role in the economic development of Israel, and in fostering scientific cooperation with other countries. For over 60 years, the American Committee has been a major source of its support.

More information about the Palm Beach Region Dinner can be obtained by calling the Palm Beach regional office at 561.210.8440.

Prof. Yonath has spent most of her scientific career working to unravel the structure of the ribosome, a complex of many components that functions as the cell’s “protein factory.” Her research has revealed how disease-causing bacteria develop resistance to antibiotics. Prof Yonath is the Martin S. and Helen Kimmel Professor of Structural Biology, and Director of the Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly.

The international Awards Jury for 2008, which was presided over by Professor Gunter Blobel, Nobel Prize in Medicine 1999, is made up of 18 eminent members of the scientific community. Professor Christian de Duve, Nobel Prize in Medicine 1974, is the Founding President of the Award.

The 2008 Award Laureates in life sciences included Professor Lihadh Al-Gazali, UAE University, United Arab Emirates; Assistant Professor V. Narry Kim, Seoul National University, Republic of Korea; Professor Ana Belen Elgoyhen, Institute for Genetic Engineering and Molecular Biology (CONICET), Buenos Aires, Argentina; and Professor Elizabeth Blackburn, University of California, San Francisco, U.S.

The Awards will be presented at a ceremony on March 6, 2008 at UNESCO headquarters in Paris by Koïchiro Matsuura, Director-General of 2008 UNESCO, and Sir Lindsay Owen-Jones, Chairman of L’Oréal.

Created in 1998, the L’OREAL-UNESCO Awards For Women in Science recognize five laureates annually, one from each of the five continents, who have contributed to the advancement of science. The candidates are proposed by an international network of more than 2,000 scientists. The Laureates serve as role models for future generations, encouraging young women around the world to follow in their footsteps. Each Laureate receives $100,000.

Some people are oblivious to the odor in the locker room after a game, while others wrinkle their noses at the slightest whiff of sweat. Research by Prof. Doron Lancet and research student Idan Menashe of the Weizmann Institute of Science’s Molecular Genetics Department, which appeared recently in PLoS Biology, has now shown that this difference is at least partly genetic.

Our sense of smell often takes a back seat to our other senses, but humans can perceive up to 10,000 different odors. Like mice, which boast a highly developed sense of smell, we have about 1,000 different genes for the smell-detecting receptors in our olfactory 'retinas.' In humans, however, over half of these genes have, in the last few million years, become defunct – some in all people, while others in just parts of the population.

Lancet and his team had their experimental volunteers sniff varying concentrations of compounds that smelled like banana, eucalyptus, spearmint, or sweat, and noted the sensitivity with which the subject was able to detect the odor. They then compared the results with genetic patterns of receptor gene loss and found that one gene (OR11H7P) appeared to be associated with the capacity for smelling sweat. When participants had two genes with disrupting mutations, they were likely to be impervious to the offending odor, while those that were hypersensitive to the smell had at least one intact gene.

The scientists noted, however, that while having at least one intact OR11H7P gene might determine whether you can tell by the smell that your loved one has just come from the gym, this is not the entire story. Women were generally slightly more sensitive to many smells than men, and some individuals of both sexes were better or worse in across-the-board acuity to all odorants. Finally (as is always the case), not all was in the genes – environmental factors were seen to play a role as well.

Repeating Genes

Huntington’s disease is a genetic time bomb: Programmed in the genes, it appears at a predictable age in adulthood, causing a progressive decline in mental and neurological function and finally death. There is, to date, no cure. Huntington’s and a number of diseases like it, collectively known as trinucleotide repeat diseases, are caused by an unusual genetic mutation: A three-letter piece of gene code is repeated over and over in one gene. Scientists at the Weizmann Institute have now proposed a mechanism that provides an explanation for the remarkable precision of the time bomb in these diseases. This explanation may, in the future, point researchers in the direction of a possible prevention or cure.

The number of repeats in Huntington’s patients ranges from 40 to over 70. Scientists have noted that, like clockwork, one can predict – by how many times the sequence repeats in a patient’s gene – both the age at which the disease will appear and how quickly the disease will progress. The basic assumption has been that the protein fragment containing the amino acid (glutamine) encoded in the repeating triplet slowly builds up in the cells until eventually reaching toxic levels. This theory, unfortunately, fails to explain some of the clinical data. For instance, it doesn’t explain why patients with two copies of the Huntington’s gene don’t exhibit symptoms earlier than those with a single copy. Plus, glutamine is produced in only some trinucleotide diseases, whereas the correlation between sequence length and onset age follows the same general curve in all of them, implying a common mechanism not tied to glutamine.

Research student Shai Kaplan in Prof. Ehud Shapiro’s lab in the Biological Chemistry Department and the Computer Sciences and Applied Mathematics Department realized the answer might lie in somatic mutations – changes in the number of DNA repeats that build up in our cells throughout our lives. The longer the sequence, the greater the chance of additional mutation, and the scientists realized that the genes carrying the disease code might be accumulating more and more DNA repeats over time, until some critical threshold is crossed.

Based on the literature on some 20 known trinucleotide repeat diseases and their knowledge of the mechanisms governing somatic mutation, Shapiro, Kaplan (who is also in the Molecular Cell Biology Department), and Dr. Shalev Itzkovitz created a computer simulation that could take a given number of genetic repeats and show both the age of onset and the way in which the disease progresses. Their findings were recently presented in PLoS Computational Biology.

The new disease model appears to fit all of the facts and to provide a good explanation for the onset and progression of all of the known trinucleotide repeat diseases. Experimentation in research labs could test this model, say the scientists and, as it predicts that all these diseases operate by somatic expansion of a trinucleotide repeat, it also suggests that a cure for all might be found in a drug or treatment that slows down the expansion process.

Bound to Identify Intruders

The first lines of defense in our immune systems are specialized mobile units that check the identity of cells to determine whether they are 'self' or 'foreign.' A team of scientists, led by Prof. Israel Pecht of the Weizmann Institute’s Immunology Department, has now revealed in fine detail how the body’s 'reconnaissance unit' continuously screens and inspects identity. These new findings may lead to deeper insights into the workings of the immune system, its function in health and malfunction in disease, as well as yielding new directions in pharmaceutical and medical research.

White blood cells called T cells employ specialized receptors called TCRs (T-cell receptors) for cell identification. TCRs bind to molecules present on all our body’s cells that act as 'self-I.D. cards.' Small fragments of bodily components bound to grooves in these molecules provide additional confirmation that the cell is ours and intruder-free. TCRs, when they examine these complexes (antigens), are able to spot foreign bits, even when one amino acid in the antigen is out of order, and can pick just one infected cell out of thousands of healthy ones, even when they harbor a previously unknown virus.

How does this interaction take place? Pecht, together with colleagues in Germany and France, has now provided the first step-by-step understanding of the process. Using a method that resolves these biological events at millisecond (a thousandth of a second) intervals, they were able to show how TCR binding progresses through time. Their findings recently appeared in the Proceedings of the National Academy of Sciences (PNAS).

The team found that binding of the TCR to the antigen takes place in two separate stages, confirming the widely held theory that the process is an 'induced fit': The original physical contact between the two molecules initiates the second step, in which conformational changes occur in the receptor as it molds itself to fit the antigen shape.

This research, says Pecht, may go a long way toward explaining a seeming paradox of long standing: How T cells can be highly specific – able to precisely identify a particular protein structure – and yet able to bind to a very wide variety of protein molecules. Additional studies based on this research may clarify the process further – shedding light on the causes of autoimmune diseases and infections such as HIV that evade the immune system, as well as advancing the search for new drugs and treatments for a variety of diseases.

The evening was emceed by senior political television correspondent Jeff Greenfield.

The night also included a commemoration of the 50th anniversary of the Weizmann Institute’s Feinberg Graduate School. Graduates of the school came from across the country to participate in a celebratory processional.

Recipients of the awards, which are known as the Sara Lee Schupf Postdoctoral Awards, have been selected by a special Feinberg Graduate School committee headed by the Weizmann Institute President’s Advisor for the Advancement of Women in Science, Prof. Hadassa Degani. The new program, funded by the Clore Foundation and S. Donald Sussman, is in its first year.

Three of the recipients conducted their doctoral studies at the Hebrew University of Jerusalem, three at the Weizmann Institute of Science, two at the Technion — Israel Institute of Technology, two at Ben-Gurion University of the Negev, and one at Tel Aviv University.

The 2007 award recipients are:

• Lilac Amirav. Title of Ph.D. thesis from the Technion — Israel Institute of Technology, Department of Chemistry: “A Novel Spray Technique for the Production of Semiconductor Nanocrystals.” Topic of postdoctoral research to be conducted at the University of California, Berkeley: “Improved Solar Energy Harvesting with a Semiconductor-Metal Nanorod Photocatalyst.”
• Yael Artzy-Randrup. Title of Ph.D. thesis from Tel Aviv University, Department of Zoology: “Modeling Spatially Structured Biological Systems.” Topic of postdoctoral research to be conducted at the University of Michigan: “The Impact of Environmental Forcing on the Dynamics and Evolution of Infectious Diseases.”
• Hadas Hawlena. Title of Ph.D. thesis from Ben-Gurion University of the Negev, Department of Life Sciences: “Interrelated Nature of Host-Parasite Interactions: Role of Ecological Factors.” Topic of postdoctoral research to be conducted at Indiana University: “Evolution of Virulence and Bacteriocins in Bacteria.”
• Ayelet Lamm (Margalit). Title of Ph.D. thesis from the Hebrew University of Jerusalem, Department of Genetics: “Functional and Structural Analysis of the Barrier-to-Autointegration Factor (BAF) Gene in C. elegans.” Topic of postdoctoral research to be conducted at Stanford University’s School of Medicine: “Genomic Imprinting and Epigenetic Modifications in C. elegans.”
• Anat Levin. Title of Ph.D. thesis from the Hebrew University of Jerusalem, School of Computer Science and Engineering: “Learning and Inference in Low-Level Vision.” Topic of postdoctoral research to be conducted at the Massachusetts Institute of Technology: “A Bayesian Analysis of Camera Light Field Samplings and Reconstructions.”
• Genela Morris. Title of Ph.D. thesis from the Hebrew University of Jerusalem, Department of Physiology: “Neural Mechanisms of Reinforcement Learning in the Basal Ganglia.” Topic of postdoctoral research to be conducted at the Neuroscience Research Center, Charite, Germany: “Evaluating the Roles of the Cortex, Basal-Ganglia and Hippocampus during Sensory Rule Learning.”
• Irena Pekker. Title of Ph.D. thesis from the Weizmann Institute of Science, Department of Plant Sciences: “Mediators of the KANADI-Morphogenetic Signaling.” Topic of postdoctoral research to be conducted at the University of Massachusetts Medical School: “The Role of the Essential RNA Helicase Armitage in Gene Silencing.”
• Adi Salomon. Title of Ph.D. thesis from the Weizmann Institute of Science, Department of Materials and Interfaces: “A Different View of Charge Transport through Alkyl Chain Monolayers.” Topic of postdoctoral research to be conducted at ISIS, France: “Surface Plasmons Molecules Coupling.”
• Genia Sklute. Title of Ph.D. thesis from the Technion Israel Institute of Technology, Department of Chemistry: “Dinuclear Zinc Catalysis: Towards the Asymmetric Cyanomethylation Reaction.” Topic of postdoctoral research to be conducted at Stanford University: “New Multicomponent Approach for the Creation of Chiral Quaternary Centers in the Carbonyl Allylation Reactions.”
• Ervin Tal-Gutelmacher. Title of Ph.D. thesis from Ben-Gurion University of the Negev, Department of Materials Engineering: “Hydrogen Interactions with Titanium Based Alloys.” Topic of postdoctoral research to be conducted at the Institute for Materials Physics, Germany: “The Effect of Hydrogen on the Grain Growth Phenomena in Titanium.”
• Neta Wexler Sal-Man. Title of Ph.D. thesis from the Weizmann Institute of Science, Department of Biological Chemistry: “Characterization of the Parameters Involved in the Oligomerization of Transmembrane Domain of Integral-Membrane Proteins.” Topic of postdoctoral research to be conducted at the University of British Columbia: “The Assembly of Type III Secretion System of Pathogenic Escherichia coli.”

The awards will help outstanding women scientists overcome the main bottleneck that impedes their professional training — conducting postdoctoral research abroad. These two or so years are considered a critical step in which up-and-coming scientists must prove their ability to conduct independent research. Yet personal, financial, and family considerations may all conspire to keep many women from being able to spend several years abroad, and the result is a relatively small number of women entering the academic track compared to men.

The Weizmann Institute’s Women in Science Program aims to change that situation. Within its framework, the Institute will now annually grant special awards that will allow outstanding women scientists to conduct postdoctoral research in leading labs around the world. The grants will give women (particularly married women or mothers of young children) incentives — financial, but also social, personal, and professional — to spend two years of training abroad. The long-term goal of the program is to invest resources in women who plan to develop their scientific careers in Israel, and to create a female leadership within the Israeli research community.

REHOVOT, ISRAEL — November 1, 2007 — Taking a chance on an experiment — this is one of the impulses that drive evolution. Living cells are, from this angle, great subjects for experimentation: Changes in one molecule can have all sorts of interesting consequences for many other molecules in the cell. Such experiments on genes and proteins have led the cell, and indeed all life, on a long and fascinating evolutionary journey.

Prof. Naama Barkai of the Weizmann Institute’s Molecular Genetics Department recently took a look at gene expression — the process in which the encoded instructions are translated into proteins — and the evolution of mechanisms in the cell for controlling that expression. Changes in genes, and thus in protein structure, are a double-edged sword: They can give cells new abilities or advantages for survival, but they can also spell disease or death for the organism. Not all genes evolve at the same rate. Indeed, some have been conserved through long stretches of evolution: Similar versions of some genes are found in yeast, plants, worms, flies, and humans. When do cells hold on to specific gene sequences, and when do they allow evolution to experiment with them? Clearly, highly conserved genes fulfill some basic, universal function for all life, and changes in their sequences have drastic consequences, involving death or the inability to multiply. How does evolution “decide” which genes need to be conserved, and which it can change freely? What keeps these genes safe from the ongoing experimentation that’s constantly carried out on other genes?

Barkai and her team discovered a sort of “risk distribution law” for evolution. They found that a genetic “phrase” that regularly shows up in the promoter region of genes (the bit of genetic code responsible for activating the gene) contains a key to gene conservation: The expression of a gene that contains the sequence TATA in its promoter is more likely to have evolved than that of a gene that does not have TATA in its promoter. In other words, the level of risk appears to written in the gene code, in a way that’s similar to financial risk analysis: When the cost of error is high, an investor’s willingness to chance the risk is low, but if the cost of a mistake is negligible, even if the chance of making one is high, the possibility of gain may make the risk worthwhile. Evolution, it seems, discovered this principle millions of years before Wall Street.

In a different study, Barkai and her research team investigated the effects of a drastic evolutionary experiment that nature sometimes performs on living cells: the doubling of an entire genome. They looked at two related species of yeast, one of which (S. cerevisiae) had undergone genome doubling millions of years ago. After the duplication, cerevisiae seem to have learned a new trick: it gained the ability to grow and multiply without oxygen.

To find if this difference is connected to changes in gene expression, the team tested 50 genes that play a role in processing oxygen in both species. They discovered one gene segment — a bit responsible for expression of these genes — that had changed in the course of the genome doubling in cerevisiae. The effects of this change were seen in over 50 genes and dramatically affected the oxygen requirements of the yeast.

The ability to live without oxygen might give cerevisiae a clear advantage over its sister yeast if there were a radical change in the make-up of the Earth’s atmosphere. But it is exactly this combination of environmental change and genetic experimentation that has fueled evolution for millions of years and is still driving it today.

Copaxone® was the first original Israeli drug to be approved by the U.S. Food and Drug Administration (FDA), and is today marketed in over 40 countries worldwide, including the U.S., Europe, Australia, Latin America, and Israel.

The drug molecule was the fruit of research by Prof. Michael Sela, Prof. Ruth Arnon, and Dr. Dvora Teitelbaum of the Weizmann Institute’s Immunology Department. It was developed for the treatment of MS by Teva, which produces and markets Copaxone® today.

“Until now, medical treatments for all kinds of diseases have relied on trial-and-error methods to determine dosage and treatment protocols,” says Prof. Ariel Miller of the Ruth and Bruce Rappaport Faculty of Medicine at the Technion, and Head of the Multiple Sclerosis and Brain Research Center, Carmel Medical Center, Haifa. “But the process of fixing the correct dosage affects the efficacy of the treatment and can lead to complications in some cases.” In the past few years, it has been shown that many drugs are not equally effective for every patient, and this variability is due, at least in part, to genetic differences. Finding medications and doses to suit the genetic makeup of each individual patient is likely to be more successful and to cause fewer side effects.

The new research, which deals with the genetic components of the response to Copaxone®, was recently published in the journal Pharmacogenetics and Genomics. It represents a significant step toward realizing this medical vision. In the collaborative study, Teva supplied DNA samples from drug-treated patients, and the genetic tests were performed at the Crown Human Genome Center of the Weizmann Institute, headed by Prof. Doron Lancet of the Institute’s Department of Molecular Genetics. The scientists used state-of-the-art equipment — the first of its kind in Israel — that allows for the rapid and accurate scanning of variations in the human genome. The scientists then examined the links between the genetic markers they found and the response of MS patients to Copaxone®. They identified several genes that are tied to a positive response to the drug.

“We analyzed the DNA sequences in 27 candidate genes from each patient participating in the trial,” said Lancet, “and we identified two genes with a high potential for determining the response to Copaxone®. In the future, it may be possible to use this method to scan the genome of MS sufferers, to predict the response levels in advance, and to optimize the dosage and treatment protocol to suit each patient personally.”

Also participating in the research were Prof. Jacques Beckmann (formerly at the Weizmann Institute); Drs. Liat Hayardeny and Dan Goldstaub of Teva; and Iris Grossman, a joint research student at the Technion and the Weizmann Institute.

Copaxone® — Interface between Past and Future

In the 1950s, Prof. Efraim Katzir of the Weizmann Institute of Science, later fourth president of the State of Israel, commenced research on the properties of proteins — the building blocks of all biological systems. This research led to the design of simple synthetic models of proteins, called “polyamino acids.” His research student at the time, Prof. Michael Sela (who later became president of the Weizmann Institute and was the recipient of, among many honors, the Israel Prize), decided to test the influence of these synthetic molecules on the immune system. This research led him to the conclusion that it might be possible to use these synthetic substances to curb symptoms of MS — an autoimmune disease in which the body’s immune system attacks proteins in the fatty layer surrounding nerve fibers, preventing the conductance of electrical signals through them.

Sela, together with his student at the time, Prof. Ruth Arnon (recipient of the Israel Prize and past vice president of the Weizmann Institute and vice president of the Association of Academies of Sciences in Asia), and Dr. Dvora Teitelbaum, conducted a long series of experiments. These experiments eventually led to the development of Copaxone®, and clinical trials carried out by Teva showed its efficacy in treating MS. At the end of the process, in 1996, Copaxone® became the first original Israeli drug to be approved by the U.S. FDA. Today, following ten years of active sales in the U.S. and 40 countries around the world, Copaxone® has made a significant contribution to the Israeli economy.

In sight and hearing, for instance, our perceptions are determined by the physical properties of waves - the length of light waves in sight, and the frequency of sound waves in hearing. But until now, there was no known physical factor that could explain how our brains sense odors. The new study, conducted by Prof. Noam Sobel of the Institute’s Neurobiology Department and his colleagues, represents a first step in understanding the physical laws that underlie our perception of smell. Their results appeared recently in the Journal of Neuroscience.

To identify the general principles by which our sense of smell is organized, the researchers began with a database of 160 different odors that had been ranked by 150 perfume and smell experts according to a set of 146 characteristics (sweetish, smoky, musty, etc.). These data were then analyzed with a statistical program that examined the variance in perception among the smell experts. The scientists found that the data fell along an axis that describes the “pleasantness rating” of the odors running from “sweet” and “flowery” at one end to “rancid” and “sickening” at the other. The same distribution along this axis, they discovered, closely describes the variation in chemical and physical properties from one substance to another. From this, the researchers found they could build a model to predict, from the molecular structure of a substance, how pleasing its smell would be perceived.

To double-check their model, Sobel and his team tested how experimental subjects assessed the pleasantness of 50 odors they had never smelled before. They found that the ratings of their test subjects fit closely with the ranking shown by their model. In other words, the researchers were able to predict the level of pleasantness quite well, even for unfamiliar smells. They noted that, although preferences for smells are commonly supposed to be culturally learned, their study showed that the responses of American, Jewish Israeli, and Muslim-Arab Israeli subjects all fit the model’s predictions to the same extent.

Sobel: “Our findings show that the way we perceive smells is at least partially hard-wired in the brain. Although there is a certain amount of flexibility, and our life experience certainly influences our perception of smell, a large part of our sense of whether an odor is pleasant or unpleasant is due to a real order in the physical world. Thus, we can now use chemistry to predict the perception of the smells of new substances.”

Is heading straight for a goal the quickest way there? If the name of the game is evolution, suggests new research at the Weizmann Institute of Science, the pace might speed up if the goals themselves change continuously.

Nadav Kashtan, Elad Noor, and Prof. Uri Alon of the Institute’s Molecular Cell Biology and Physics of Complex Systems Departments create computer simulations that mimic natural evolution, allowing them to investigate processes that, in nature, take place over millions of years. In these simulations, a population of digital genomes evolves over time towards a given goal: to maximize fitness under certain conditions. Like living organisms, genomes that are better adapted to their environment may survive to the next generation or reproduce more prolifically. But such computer simulations, though sophisticated, don’t yet have all the answers. Achieving even simple goals may take thousands of generations, raising the question of whether the three-or-so billion years since life first appeared on the planet is long enough to evolve the diversity and complexity that exist today.

Evolution takes place under changing environmental conditions, forcing organisms to continually readapt. Intuitively, this would slow things down even further, as successive generations must switch tack again and again in the struggle to survive. But when Kashtan, Noor, and Alon created a simulation in which the goals changed repeatedly, they found that its evolution actually speeded up. They even found that the more complex the goal – i.e., the more generations needed reach it under fixed conditions – the faster evolution accelerated in response to changes in that goal.

Computerized evolution ran fastest, the scientists found, when the changes followed a pattern they believe may be pervasive in nature. In previous research, Kashtan and Alon had shown that evolution may often be modular – involving adjustments to standard parts, rather than wholesale remodeling. They theorized that the forces acting on evolution may be modular as well, and for each goal, they defined subgoals that could each change in relation to the others. “In an organism, for example, you might classify these subgoals as the need to eat, the need to keep from being eaten, and the need to reproduce. The same subgoals must be fulfilled in each new environment, but there are differences in nuance and combination," says Kashtan. "We saw a large speedup, for instance, when we repeatedly exchanged an ‘OR’ for an ‘AND’ in the computer code defining our goals, thus changing the relationship between subgoals.”

Although the main aim of this research, which appeared recently in the Proceedings of the National Academy of Sciences (PNAS), was to shed light on theoretical questions of evolution, it may have some practical implications, particularly in engineering fields in which evolutionary tools are commonly used for systems design, and in computer science, by providing a possible way to accelerate optimization algorithms.

Shrinking Giants, Exploding Dwarves
When white dwarf stars explode, they leave behind a rapidly expanding cloud of “stardust” known as a Type Ia supernova. These exploding events, which shine billions of times brighter than our sun, are all presumed to be extremely similar, and thus have been used extensively as cosmological reference beacons to trace distance and the evolution of the Universe.

Astronomers have now – for the first time ever – provided a unique set of observations obtained with the ESO Very Large Telescope in Chile and the 10-meter Keck telescope in Hawaii, enabling them to find traces of the material that had surrounded a white dwarf star before it exploded. Their data set is unique in that no Type Ia supernova event has ever been observed at this level of detail over a several-month period following the explosion.

These observations support a widely accepted model proposing that a white dwarf star interacts with a companion star – a red giant. Due to the white dwarf’s strong gravitational pull, this companion star continuously loses mass through “force feeding” its gases to the white dwarf. When the mass of the white dwarf grows past a critical value, it explodes.

Through their observations, which took place over the course of four months, and combined with archival data, the astronomers detected the presence of a number of expanding shells surrounding a Type Ia supernova event. The makeup of these shells suggests they are the remnants of the red giant star that fed the white dwarf.

These results were recently published in the journal Science. The data were collected by two teams of researchers: one at ESO, headed by Dr. Ferdinando Patat, and one at the California Institute of Technology, led by Dr. Avishay Gal-Yam. Dr. Gal-Yam has recently joined the Weizmann Institute of Science as a senior scientist in the Condensed Matter Physics Department.

A Gene for Metastasis
Weizmann Institute Scientists Reveal the Actions of a Key Player in Colorectal Cancer

Colorectal cancer is one of the most prevalent cancers in the Western world. The tumor starts off as a polyp but then turns into an invasive and violent cancer, which often spreads to the liver. In an article recently published in the journal Cancer Research, Prof. Avri Ben-Ze’ev and Dr. Nancy Gavert of the Weizmann Institute’s Molecular Cell Biology Department reveal mechanisms that help this cancer metastasize.

In a majority of cases, colorectal cancer is initiated by changes in a key protein – beta-catenin. One of the roles of this protein is to enter the cell nucleus and activate gene expression. But in colorectal and other cancers, beta-catenin over-accumulates in the cell and inappropriately activates genes, leading to cancer.

Surprisingly, one of the genes activated by beta-catenin, which had been previously detected in colorectal cancer cells by Ben-Ze’ev’s group, codes for a receptor called L1-CAM. This receptor is a protein usually found on nerve cells, where it plays a role in nerve cell recognition and motility. What is this receptor doing in cancer cells? Ben-Ze’ev’s previous research had shown that L1-CAM is only expressed on certain cells located at the invasive front of the tumor tissue, hinting that it could be an important player in metastasis.

In this study, the scientists found that colorectal cancer cells engineered to express the L1-CAM gene indeed spread to the liver, while those cells lacking L1-CAM did not.

In collaboration with Prof. Eytan Domany and research student Michal Sheffer of the Institute’s Physics of Complex Systems Department, Ben-Ze’ev then compared the expression of genes induced by L1-CAM in cultured colon cancer cells to those in 170 samples of colorectal cancer tissue removed from patients, and in 40 samples of normal colon tissue. Out of some 160 genes induced by L1-CAM, about 60 were highly expressed in the cancerous tissue, but not in normal colon tissue. Ben-Ze’ev plans to conduct further research into the role of these genes, to uncover L1-CAM’s function in metastasis.

A team of scientists headed by Prof. Idit Shachar of the Weizmann Institute’s Immunology Department and Dr. Michal Haran of the Hematology Institute of the Kaplan Medical Center recently discovered what makes these cancer cells stay alive. They then launched a targeted attack on the survival mechanism they discovered and succeeded in significantly raising cancer cell mortality rates. Their findings, which appeared recently in Proceedings of the National Academy of Sciences (PNAS), may lead to future treatments for this disease, as well as for other diseases in which B lymphocytes accumulate in the blood.

In previous research, Shachar had found that a specific receptor - a protein on the outer surface of healthy B cells - fulfills a crucial role in helping these cells to survive. She wondered if the same protein might also be a central player in the abnormally high survival rates of cancerous B cells.

Members of Shachar’s research team, including Inbal Binsky, Diana Starlets, Yael Gore, and Frida Lantner, together with Kaplan Medical Center doctors Haran, Lev Shvidel, Prof. Alan Berrebi, and Nurit Harpaz, scientists from Yale University, and David Goldenberg of the Garden State Cancer Center in New Jersey, examined B cells taken from chronic lymphocytic leukemia patients. They discovered that, even in the earliest stages of the disease, these cells have an unusually high level of both the survival receptor and another protein that binds to the receptor. The scientists found that this protein, in binding to the receptor, initiates a series of events within the cell that leads to enhanced cell-survival capabilities. For instance, in one of these events, a substance is produced that helps to regulate the cell’s lifespan. This substance causes another protein to be produced, which then prevents the self-destruct program from being activated.

The team treated the chronic lymphocytic leukemia cells with an antibody that attached to the survival receptor, blocking its activity and causing the cancer cell death rate to soar.

The antibodies they used are produced by the firm Immunomedics, in New Jersey, and are currently entering clinical trials for the treatment of several different types of cancer. Following this research, which has revealed the mechanism for the antibody’s actions, the company is planning trials for chronic lymphocytic leukemia, as well.

Shachar: “The abnormally elevated levels of this receptor seem to be important factors in the development of this disease, right from the beginning, and they are responsible for the longevity of these cancerous B cells. Blocking the receptor or other stages in the pathway they activate might be a winning tactic, in the future, in the war against cancers involving B cells.”

Dudai and research student Reut Shema, together with Todd Sacktor of the State University of New York (SUNY) Downstate Medical Center, trained rats to avoid certain tastes. They then injected a drug to block a specific protein into the taste cortex -- an area of the brain associated with taste memory. They hypothesized, on the basis of earlier research by Sacktor, that this protein, an enzyme called PKMzeta, acts as a miniature memory “machine” that keeps memory up and running. An enzyme causes structural and functional changes in other proteins: PKMzeta, located in the synapses -- the functional contact points between nerve cells -- changes some facets of the structure of synaptic contacts. It must be persistently active, however, to maintain this change, which is brought about by learning. Silencing PKMzeta, reasoned the scientists, should reverse the change in the synapse. And this is exactly what happened: Regardless of the taste the rats were trained to avoid, they forgot their learned aversion after a single application of the drug. The technique worked just as successfully a month after the memories were formed (in terms of life span, more or less analogous to years in humans), and all signs so far indicate that the affected unpleasant memories of the taste had indeed disappeared. This is the first time that memories in the brain were shown to be capable of erasure so long after their formation.

“This drug is a molecular version of jamming the operation of the machine,” says Dudai. “When the machine stops, the memories stop as well.” In other words, long-term memory is not a one-time inscription on the nerve network, but an ongoing process which the brain must continuously fuel and maintain. These findings raise the possibility of developing future, drug-based approaches for boosting and stabilizing memory.

For a cell such as a cancer cell to migrate, it first must detach itself from neighboring cells and the intercellular material to which it is anchored. Before it can do this, it receives an order from outside the cell saying: “prepare to move.” This signal takes the form of a substance called a growth factor, which, in addition to controlling movement, can activate a number of processes in the cell including division and differentiation. The growth factor attaches to a receptor on the cell wall, initiating a sequence of changes in the cellular structure. The cell’s internal skeleton -- an assembly of densely-packed protein fibers -- comes apart and the protein fibers then form thin threads on the outside of the cell membrane that push the cell away from its neighbors. In addition, a number of protein levels change: some get produced in higher quantities and some in lower.

To understand which proteins are modulated by the growth factor and the nature of the genetic mechanisms involved in cancer cell migration, a team of researchers pooled their knowledge and resources. This team, headed by Prof. Yosef Yarden of the Weizmann Institute’s Biological Regulation Department and his research group, included Drs. Menachem Katz, Ido Amit, and Ami Citri; Tal Shay, a student in the group of Prof. Eytan Domany of the Physics of Complex Systems Department; and Prof. Gideon Rechavi of the Chaim Sheba Medical Center at Tel Hashomer.

To begin with, the team mapped all of the genetic changes that take place in the cell after the growth factor signal is received. As they sifted through the enormous amount of data they received, including details on every protein level that went up or down, one family of proteins stood out. Tensins, as they are called, are proteins that stabilize the cell structure. But to the scientists' surprise, the amounts of one family member rose dramatically while, at the same time, the levels of another dropped.

Despite the familial similarity, the team found a significant difference between them. The protein that drops off has two arms: One arm attaches to the protein fibers forming the skeleton, and the other anchors itself to the cell membrane. This action is what stabilizes the cell’s structure. The protein that increases, on the other hand, is made up of one short arm that only attaches to the anchor point on the cell membrane. Rather than structural support, this protein acts as a kind of plug, blocking the anchor point, and allowing the skeletal protein fibers to unravel into the threads that push the cells apart. The cell is then free to move, and, if it’s a cancer cell, to metastasize to a new site in the body.

In experiments with genetically engineered cells, the scientists showed that the growth factor directly influences levels of both proteins, and that these, in turn, control the cells’ ability to migrate. Blocking production of the short tensin protein kept cells in their place, while overproduction of this protein plug increased their migration.

Next, the scientists carried out tests on tumor samples taken from around 300 patients with inflammatory breast cancer, a rare but swift and deadly form of the disease, which is associated with elevated growth factor levels. The scientists found a strong correlation between high growth factor activity and levels of the “plug” protein. High levels of this protein, in turn, were associated with cancer metastasis to the lymph nodes -- the first station of migrating cancer cells as they spread to other parts of the body.

In another experiment, the scientists examined the effects of drugs that block the growth factor receptors on the cell walls. In patients who received these drugs, the harmful “plug” proteins had disappeared from the cancer cells. Prof. Yarden: “The mechanism we identified is clinically important. It can predict the development of metastasis and possibly how the cancer will respond to treatment.” This discovery may, in the future, aid in the development of drugs to prevent or reduce the production of the unwanted protein, and thus prevent metastasis in breast or other cancers.

Also participating in this research were Sara Lavi, Nir Ben-Chetrit, Gabi Tarcic, Dr. Moshit Lindzen, and Roi Avraham from Prof. Yarden’s group; Tal Shay from Prof. Domany’s group; Dr. Ninette Amariglio and Dr. Jasmine Jacob-Hirsch from Prof. Rechavi’s group at Sheba Medical Center; a research team from the Institute of Molecular Pathology and Immunology and the Medical Faculty at Porto University, Portugal; and researchers from the University of California at Davis, Boston University, and GlaxoSmithKline, North Carolina.

Often, things can be improved by a little “contamination.” Steel, for example, is iron with a bit of carbon mixed in. To produce materials for modern electronics, small amounts of impurities are introduced into silicon a process called doping. It is these impurities that enable electricity to flow through the semiconductor and allow designers to control the electronic properties of the material.

Scientists at the Weizmann Institute of Science, together with colleagues from the U.S., recently succeeded in being the first to implement doping in the field of molecular electronics -- the development of electronic components made of single layers of organic (carbon-based) molecules. Such components might be inexpensive, biodegradable, versatile, and easy to manipulate. The main problem with molecular electronics, however, is that the organic materials must first be made sufficiently pure, and then ways must be found to successfully dope these somewhat delicate systems.

This is what Prof. David Cahen and postdoctoral fellow Dr. Oliver Seitz of the Weizmann Institute’s Material and Interfaces Department, together with Drs. Ayelet Vilan and Hagai Cohen from the Chemical Research Support Unit and Prof. Antoine Kahn from Princeton University, did. They showed that such contamination is indeed possible, after they succeeded in purifying the molecular layer to such an extent that the remaining impurities did not affect the system’s electrical behavior. The scientists doped the “clean” monolayers by irradiating the surface with ultraviolet (UV) light or weak electron beams, changing chemical bonds between the carbon atoms that make up the molecular layer. These bonds ultimately influenced electronic transport through the molecules.

This achievement was recently described in the Journal of the American Chemical Society. The researchers foresee that this method may enable scientists and electronics engineers to substantially broaden the use of these organic monolayers in the field of nanoelectronics. Dr. Seitz: “If I am permitted to dream a little, it could be that this method will allow us to create types of electronics that are different, and maybe even more environmentally friendly, than the standard ones that are available today.”

Opposites Interfere
In a classic physics experiment, photons (light particles), electrons, or any other quantum particles are fired, one at a time, at a sheet with two slits cut in it that sits in front of a recording plate. For photons, a photographic plate reveals an oscillating pattern (bands of light and dark) a sign that each particle, behaving like a wave, has somehow passed through both slits simultaneously and interfered, canceling the light in some places and enhancing it in others.

If single quantum particles can exist in two places at once, and interfere with themselves in predictable patterns, what happens when there are two quantum particles? Can they interfere with each other? Prof. Mordehai Heiblum of the Weizmann Institute’s Condensed Matter Physics Department and his research team have been experimenting with electrons fired across special semiconductor devices. Quantum mechanics predicts that two electrons can indeed cause the same sort of interference as that of a single electron on one condition: that the two are identical to the point of being indistinguishable. Heiblum and his team showed that, because of such interference, these two particles are entangled the actions of one are inextricably tied to the actions of the other even though they come from completely different sources and never interact with each other. The team’s findings recently appeared in the journal Nature.

Dr. Izhar Neder and Nissim Ofek, together with Drs. Yunchul Chung, Diana Mahalu, and Vladimir Umansky, fired such identical electron pairs from opposite sides of their device, toward detectors that were placed two to a side of the device. In other words, each pair of detectors could detect the two particles arriving in one of two ways: particle 1 in detector 1 and particle 2 in detector 2, or, alternatively, particle 2 in detector 1 and particle 1 in detector 2. Since these two “choices” are indistinguishable, the choices interfere with each other in the same way as the two possible paths of a single quantum particle interfere. The scientists then investigated how the choice of one particle affected the pathway taken by the other, and found strong correlations between them. These correlations could be affected by changing, for example, the length of the path taken by one particle. This is the first time an oscillating interference pattern between two identical particles has been observed, proving, once again, the success of quantum theory.

When Off-Target is Right On
All organisms perform intricate molecular computations to survive. Unlike manmade computer components that are meticulously ordered on a chip, the molecules that make up biological “computers” are diffuse within the cell. Yet these must pinpoint and then bind to specific counterparts while swimming in the cell’s thick, erratic molecular stew something like finding a friend in a Tokyo subway station during rush hour.

In the classical view of molecular recognition, the binding molecules fit each other like a lock and key. Half a century of research has shown, however, that in numerous cases, the molecules need to deform in order to bind, as the key is not an exact fit for the molecular lock. Why would evolution choose such an inexact system?

The work of Dr. Tsvi Tlusty and research student Yonatan Savir of the Weizmann Institute’s Physics of Complex Systems Department, suggests a possible answer. A simple biophysical model they developed indicates that, in picking out the target molecule from a crowd of look-alikes, the recognizer has an advantage if it’s slightly off-target. This may appear to be counterintuitive: Why search for a key that does not match its lock exactly, and then require that the imperfect key warp its shape to fit the lock? The researchers’ model shows that the key’s deformation actually helps in discerning the right target. Although the energy required to deform the molecular key slightly lowers the probability of its binding to the right target, it also reduces the probability that it will bind to a wrong one by quite a bit. Thus, the quality of recognition i.e., the ratio of the right to wrong binding probabilities increases. The research was published recently in the journal PLoS ONE.

This simple mechanism is coined “conformational proofreading” and may explain the observed deformations in many biological recognition systems. Furthermore, conformational proofreading may turn out be a crucial factor affecting the evolution of biological systems, and it may also be useful in the design of artificial molecular recognition systems.

Live Broadcasts
To help molecular biologists in the difficult task of keeping abreast of current events in the world of cells and organisms, they employ reporter genes to “broadcast” specific happenings. For example, if a scientist is interested in the whereabouts and activities of a certain gene, the reporter “follows” it, and when this gene is activated in any way, the reporter gene produces an easily detectable protein, such as green fluorescent protein (GFP). The scientists are then able to “read” this “report” and learn about the specific events that are occurring and in what regions.

The light given off by these proteins is scattered in the tissue, however, reducing the resolution of many images. An alternative to fluorescent proteins is reporters that would be detectable via magnetic resonance imaging (MRI). But for most of the candidate reporters proposed so far, a second material needs to be administered in addition to the reporter gene to allow the MRI to detect its signals. Unfortunately, processes such as fetal development and those that take place within the central nervous system present barriers to these additional substances

Prof. Michal Neeman and Dr. Batya Cohen of the Weizmann Institute’s Biological Regulation Department, along with Ph.D. students Keren Ziv and Vicki Plaks and colleagues, have now developed genetically modified mice that carry a promising candidate reporter named ferritin, which could circumvent these problems. Ferritin works by sequestering iron from cells. When it is overexpressed, iron uptake increases, causing signal changes in the surrounding environment that can be detected by MRI, without the need to administer an additional substance.

As recently described in the journal Nature Medicine, ferritin has so far successfully broadcast live reports via MRI detection from the liver, endothelial cells, and even during fetal development in pregnant mice, without the need for additional substances.

"Norman Cohen has served the American Committee and the Weizmann Institute in different capacities for over three decades. His help has been crucial to our success and is simply immeasurable,” Robert B. Machinist, American Committee Chairman, said. “Now, I am delighted that Pennie has accepted the position of President. She brings commitment, energy, and real organizational skills to our leadership team.”

Pennie Abramson has dedicated her time and energy to the American Committee for the Weizmann Institute of Science for 25 years. She is a longstanding member of the Board of Directors’ Executive Committee and has also chaired the American Committee’s Washington, D.C. Region. Along with her husband, Gary Abramson, she is a member of the President’s Circle. Ms. Abramson recently concluded her tenure as Vice-Chair of National Programs, where she led U.S. donor program initiatives that helped raise awareness and significant support for the Institute.

Pennie Abramson’s philanthropic interests are wide-ranging. She is the current Chairperson of the Montgomery County Public Schools Educational Foundation, and is an active member of the Fisher Island Philanthropic Foundation, which supports children’s charities based in Miami. Ms. Abramson is also a member of the Board of Trustees for Friends of Cancer Research and has served on the boards of the Make-A-Wish Foundation and Imagination Station. She has acted as Chair of the Women’s Division for State of Israel Bonds and has lent valuable leadership support to the American Cancer Society and the Leukemia Society of America. Ms. Abramson has been married to Gary for 37 years. They have three children and one grandchild.

In her role as President, Ms. Abramson will advocate for the Weizmann Institute of Science and advance its mission of Science for the Benefit of Humanity. She will particularly focus her efforts on representing the Weizmann Institute to major donors around the country.

Outgoing President Norman Cohen has been involved with the Weizmann Institute since 1970, when he endowed the Norman D. Cohen Chair in Computer Science. Since then, he has filled several vital leadership roles, including Chairman of the American Committee and International Deputy Chairman of the Weizmann Institute. He is a member of the President’s Circle, an International Governor, and a member of the Executive Committee of the American Committee’s Board of Directors. In 1990, the Weizmann Institute awarded him an Honorary Doctorate. Professionally, Mr. Cohen is one of the founders of Lechmere Sales, a chain of New England-based retail stores. He resides in both New York and Palm Beach. The Weizmann Institute has benefited greatly from his counsel, guidance, business acumen, and loyalty.

The numbers of women and men completing graduate degrees (M.S. and Ph.D.) in the sciences are close to even. But in Israel, as in the rest of the world, relatively few women end up on the track to academic advancement, and their representation on the higher levels of academic faculties is abysmally low.

A new, Israel-wide initiative put forward by the Weizmann Institute to help fill the ranks of outstanding women scientists has been established with the support of the Clore Foundation and S. Donald Sussman. This year, as part of this Weizmann Institute of Science Women in Science Program, ten young women will receive Sara Lee Schupf Postdoctoral Awards. Any young woman who has completed a Ph.D. in an Israeli academic institution in one of the natural or exact sciences, and who has been accepted to postdoctoral studies abroad, is eligible to apply. The awards will average about $20,000 a year and are meant to supplement scholarships received from foundations or host institutions, to assist women, particularly those with families, in coping with the added financial burden.

Bottleneck
The two or so years a scientist spends abroad conducting postdoctoral research is considered a critical step to career success, in which the up-and-coming scientist gains independence and is exposed to the international scientific community in which she must prove herself. Yet this stage can be a bottleneck for women, especially as many have spouses and young children by this point in life. Personal, financial, and family considerations may all conspire to keep these women from being able to spend several years abroad, and the result is a relatively small number of women entering the academic track.

The Sara Lee Schupf Postdoctoral Awards, conferred within the framework of the Weizmann Institute of Science Women in Science Program funded by the Clore Foundation and S. Donald Sussman, aim to change that situation. The grants will give women incentives financial, but also social, personal, and professional to engage in postdoctoral research in leading labs around the world. The long-term goal of the program is to invest resources in women who plan to develop their scientific careers in Israel, and to create a feminine leadership within the Israeli research community.

The Weizmann Institute is now calling for women who have completed a Ph.D. in science in an Israeli university to submit their candidacy for one of these awards. A special selection committee at the Institute, headed by the President’s Advisor for the Advancement of Women in Science, Prof. Hadassa Degani, will evaluate the applications and choose ten outstanding women, who will receive their awards in October 2007.

Nerve cells (neurons) have long, thin extensions called axons that can reach up to a meter and or more in length. Often, these extensions are covered by myelin, which is formed by a group of specialized cells called glia. Glial cells revolve around the axon, laying down the myelin sheath in segments, leaving small nodes of exposed nerve in between. More than just protection for the delicate axons, the myelin covering allows nerve signals to jump instantaneously between nodes, making the transfer of these signals quick and efficient. When myelin is missing or damaged, the nerve signals can’t skip properly down the axons, leading to abnormal function of the affected nerve and often to its degeneration.

In research published recently in Nature Neuroscience, Weizmann Institute scientists Prof. Elior Peles, graduate student Ivo Spiegel, and their colleagues in the Molecular Cell Biology Department and in the United States, have now provided a vital insight into the mechanism by which glial cells recognize and myelinate axons.

How do the glial cells and the axon coordinate this process? The Weizmann Institute team found a pair of proteins that pass messages from axons to glial cells. These proteins, called Necl1 and Necl4, belong to a larger family of cell adhesion molecules, so called because they sit on the outer membranes of cells and help them to stick together. Peles and his team discovered that even when removed from their cells, Necl1, normally found on the axon surface, and Necl4, which is found on the glial cell membrane, adhere tightly together. When these molecules are in their natural places, they not only create physical contact between axon and glial cell, but also serve to transfer signals to the cell interior, initiating changes needed to undertake myelination.

The scientists found that production of Necl4 in the glial cells rises when they come into close contact with an unmyelinated axon, and as the process of myelination begins. They observed that if Necl4 is absent in the glial cells, or if they blocked the attachment of Necl4 to Necl1, the axons that were contacted by glial cells did not myelinate. In the same time period, myelin wrapping was already well underway around most of the axons in the control group.

“What we’ve discovered is a completely new means of communication between these nervous system cells,” says Peles. “The drugs now used to treat MS and other degenerative diseases in which myelin is affected can only slow the disease, but not stop or cure it. Today, we can’t reverse the nerve damage caused by these disorders. But if we can understand the mechanisms that control the process of wrapping the axons by their protective sheath, we might be able to recreate that process in patients.”

True to his favorite saying—“Don’t give until it hurts; give until it feels good”—Mr. Gardner’s support for the Weizmann Institute of Science reflects his enthusiasm for basic research. “I just love basic science,” he says. The self-proclaimed “physics geek” explains that “basic research is the underlying kingpin to everything that’s developed.”

Mr. Gardner has personal motivations for supporting the Weizmann Institute as well: his wife battled lymphoma three times and has been cancer-free for five years, thanks in part to the drug Rituximab, developed at the Weizmann Institute. The scientist responsible for Rituximab spoke at a symposium organized by the American Committee that the Gardners attended, and the couple felt the direct impact of the Institute’s credo: “Science for the Benefit of Humanity.”

His appointment to the Board follows several years of participation in American Committee activities, both in Austin and at the annual Global Gatherings hosted by different Regional branches of the Committee.

Aside from the Weizmann Institute of Science, Mr. Gardner’s primary philanthropic interest is Texas A&M University, where he received his B.A; he now serves on the Board of the Texas A&M Research Foundation. He is involved with the University’s Hillel, and has been active in many other causes as well, including local Hospice programs, Extend-A-Care, the Financial Planning Association, Temple Beth Israel, and the American Israel Public Affairs Committee (AIPAC). He is the former President of B’nai B’rith and of the Jewish Federation of Austin and has received the Jewish Community Council’s “Community Leadership Award.”

By coordinating local receptions that feature visiting Weizmann Institute scientists, he hopes to promote “the excitement of science” to a wide variety of Central Texans who may not be familiar with the Weizmann Institute. As a Board member, Mr. Gardner will advocate the humanitarian mission of the American Committee for the Weizmann Institute of Science, and help shape its financial resource development strategies.

Prof. Mordechai “Moti” Liscovitch and graduate student Oran Erster of the Weizmann Institute’s Biological Regulation Department, together with Dr. Miri Eisenstein of Chemical Research Support, have recently developed a unique “switch” that can control the activity of any protein, raising it several-fold or stopping it almost completely. The method provides researchers with a simple and effective tool for exploring the function of unknown proteins, and in the future the new technique may find many additional uses.

The switch has a genetic component and a chemical component: Using genetic engineering, the scientists insert a short segment of amino acids into the amino acid sequence making up the protein. This segment is capable of binding strongly and selectively to a particular chemical drug, which affects the activity level of the engineered protein by increasing or reducing it. When the drug is no longer applied, or when it is removed from the system, the protein returns to its natural activity level.

As reported recently in the journal Nature Methods, the first stage of the method consists of preparing a set of genetically engineered proteins (called a “library” in scientific language) with the amino acid segment inserted in different places. In the second stage, the engineered proteins are screened to identify the ones that respond to the drug in a desired manner. The researchers have discovered that in some of the engineered proteins the drug increased the activity level, while in others this activity was reduced. Says Prof. Liscovitch: “We were surprised by the effectiveness of the method it turns out that a small set of engineered proteins is needed to find the ones that respond to the drug. With their greater resources, biotechnology companies will be able to create much larger sets of engineered proteins in order to find one that best meets their needs.”

The method developed by the Weizmann Institute scientists is ready for immediate use, both in basic biomedical research and in the pharmaceutical industry, in the search for proteins that can serve as targets for new drugs. Beyond offering a potent tool that can be applied to any protein, the method has an important advantage compared with other techniques: It allows the total and precise control over the activity of an engineered protein. Such activity can be brought to a desired level or returned to its natural level, at specific locations in the body and at specific times all this by giving exact and well-timed doses of the same simple drug.

In addition, the method could be used one day in gene therapy. It may be possible to replace damaged proteins that cause severe diseases with genetically engineered proteins, and to control these proteins’ activity levels in a precise manner by giving appropriate doses of the drug. Another potential future application is in agricultural genetic engineering. The method might make it possible, for example, to create genetically engineered plants in which the precise timing of fruit ripening would be controlled using a substance that increases the activity of proteins responsible for ripening. Moreover, numerous proteins are used in industrial processes, as biological sensors and in other applications. The possibility of controlling these applications strengthening or slowing the rate of protein activity in an immediate and reversible manner can be of great value.

“I am delighted that Larry has agreed to accept the challenge of chairing the American Committee,” Mr. Machinist said. “Larry’s longstanding commitment to the Weizmann Institute makes him uniquely qualified to serve as Chairman in the U.S., and to work closely with the new administration at the Institute, led by Mandy Moross, Chair of the Board of Governors.”

Mr. Blumberg has been intimately involved with the Weizmann Institute for more than 25 years, honoring a family tradition of friendship with the Institute. His father, Gerald Blumberg, joined the Board of the American Committee in the 1970’s and served as Vice President. Now, at age 95, Gerald Blumberg is an Honorary Vice Chairman of the Committee and a Governor Emeritus of the Weizmann Institute. Gerald Blumberg and his wife, Rhoda, as well as Lawrence Blumberg and his wife, Robin Lynn, are members of the American Committee’s President’s Circle.

Mr. Blumberg devotes himself to both national and international support for the Weizmann Institute. In 1981, he attended a symposium entitled “The Impact of Science Upon Our Lives,” which introduced him to the importance of basic scientific research and the critical role the Weizmann Institute plays both in science and in the development of the State of Israel. The symposium inspired Mr. Blumberg, and his passion has not wavered. He travels frequently to Israel and to the Institute’s campus in Rehovot. He regularly attends meetings of the International Board of Governors. Mr. Blumberg is the Vice-Chairman of the Institute’ s Executive Committee and recently completed the maximum term of nine years as a Deputy Chairman of the Board of Governors. In 2001, the Weizmann Institute awarded Mr. Blumberg a Ph.D. Honoris Causa in recognition of his outstanding leadership and philanthropic commitment.

Mr. Blumberg has proven a dedicated and determined friend to the American Committee, as well. He is an enthusiastic participant in U.S. regional events, having served as Chair of the New York Region. Since joining the national Board of Directors in 1981, Mr. Blumberg has served on its Executive Committee and Administrative Council and led the Planned Giving Committee and the New York Executive Committee. He has acted as Secretary, Vice-President, and General Counsel.

As managing partner of Gerald & Lawrence Blumberg, LLP (www.glblumberg.com), Mr. Blumberg advises and represents individuals, families, and charitable organizations, particularly in estate planning, real estate, family-owned businesses and charitable giving. Mr. Blumberg began his career representing consumers’ interests in Washington, D.C. with the U.S. Federal Trade Commission.

Mr. Blumberg was a University Scholar at NYU’s University College of Arts and Sciences. He received his J.D. from Columbia Law School, where he was a Harlan Fiske Stone Scholar. Mr. Blumberg is married to Robin Lynn, who works in the field of urban planning and advocacy for the Municipal Art Society of New York. They have three children, Daniel, Carla and Ilana.

How myoblasts identify other myoblasts and how they cling together had been established, but the way that the cell membranes fuse into one has remained a mystery. Now, a study by Weizmann Institute scientists has shed light on this mystery. The study was carried out by research student Rada Massarwa and lab technician Shari Carmon under the guidance of Dr. Eyal Schejter and Prof. Ben-Zion Shilo of the Institute’s Molecular Genetics Department, with help from Dr. Vera Shinder of the Electron Microscopy Unit. The cells’ system for identifying other myoblasts and sticking to them consists of protein molecules that poke through the outer cell membrane one end pointing out and the other extending into the body of the cell. These recognition proteins anchor the cells together, but what makes myoblasts open their doors to each other and merge into one cell?

The scientists discovered that a protein called WIP, which attaches to the internal part of the myoblast recognition protein, plays a key role in muscle cell fusion. WIP communicates between the recognition protein and the cell’s internal skeleton, which is made of tough, elastic fibers composed of a protein called actin. The skeletal actin applies force to the abutting cell membranes, opening and enlarging holes that allow the cells to merge. The Weizmann Institute team found that the WIP protein is activated by an external signal once myoblasts identify and attach to each other. Only when it receives this signal does WIP hook the actin fibers in the skeleton up to the myoblast recognition protein, allowing cell fusion to proceed.

The WIP protein has been conserved evolutionarily. In other words, versions of it exist in all animals, from microorganisms such as yeast, through worms and flies, and up to humans. This means that the protein fulfills a function necessary for life but also, say the scientists, because of this conservation, studies conducted on this protein in fruit flies can teach us quite a bit about how it works in humans.

To further examine the role of WIP, the scientists knocked out the gene responsible for producing it in fruit flies. In flies that did not make the protein, normal muscle fibers were not produced. WIP-deficient myoblasts continued to identify and cozy up to one another, but fusion between cell membranes did not take place, and multi-nucleated muscle fibers failed to form. An article describing these findings appeared today in the journal Developmental Cell.

This study, which improves our understanding of the process of muscle formation, may assist in the future, in devising new and advanced methods for healing muscle. Specifically, these might include ways of fusing stem cells with injured or degenerated muscle fibers.

Fusion between cell membranes plays a key role in development of different kinds of bone cells, placental cells, and immune system cells, as well as in fertilization and in the penetration of viruses into living cells. Understanding how membrane fusion takes place may one day lead to the development of ways to encourage the process when it’s needed or hinder it when it’s likely to cause harm.

The principal objectives of the seminar are:

-Introduce methods of incorporating cutting-edge scientific research into science education;

-Bring innovative teaching/learning strategies and models into the classroom;

-Establish an international, professional network of science teachers;

-Foster collaboration between science teachers, schools, and students through affiliation with the Davidson Institute of Science Education at the Weizmann Institute

Details
The seminar will be held from Monday, July 23 through Tuesday, July 31, 2007. International participants should arrive at the Weizmann Institute on Sunday, July 22, 2007.

Thanks to generous support provided by The Jess & Sheila Schwartz Family Foundation, program costs are fully subsidized. Accommodations are on the campus of the Weizmann Institute. Participants must purchase their own airfare and pay a registration fee of $120.

Secondary school science teachers interested in participating in the International Seminar should complete information and registration forms before April 30, 2007. Notification of acceptance will be sent upon receipt of registration fee.

Please note: Number of participants is limited. Registration fees will be returned if all spaces have been filled.

For further information, please contact Tina Begleiter at (212) 895-7934 or tina@acwis.org, or go to http://www.weizmann.ac.il/davidson

The cells, called osteoclasts, have some unique features not seen in any other cell type. Osteoclasts move around the bone until they reach a site where they sense that their services are required, at which point they undergo a transformation called polarization. The polarized osteoclast sticks itself tightly to the bone, while an impermeable ring forms around the cell perimeter. This ring functions to keep the bone-eating acids and enzymes produced between the cell and the bone confined to the demolition site.

How does this ring form? To solve the mystery, Prof. Benjamin Geiger, Dean of Biology, and Prof. Lia Addadi of the Structural Biology Department, together with doctoral students Chen Luxenburg and Dafna Geblinger, and with the assistance of Dr. Eugenia Klein (electron microscopy unit), Prof. Dorit Hanein and Karen Anderson of the Burnham Institute, San Diego applied two different observation methods to samples of stripped-down, polarized osteoclasts: electron microscope imaging that allowed them to see fine details of the ring structure, and a light microscope method in which specific features glow. Because each method captures different information at a different scale, combining them was tricky, but the two together gave them a much more extensive picture than either alone.

They found that the ring is composed of dot-like structures called podosomes, anchored to the cell membrane. When the osteoclast is on the move, these little dots amble randomly around the cell, but when the cells prepare to dissolve the bone, they make a beeline for the edge. Scientists had been unsure how podosomes were involved in ring formation or, if they did form the ring, whether they somehow fused together or kept their individual shapes. The research team’s findings showed clearly that the ring is made of individual podosomes held together by interconnecting protein filaments they throw out to each other.  “The podosomes are like folk dancers,” says Geiger. “As soon as the music starts up, they join hands and form a tight circle. From afar, a circle of dancers looks like a blur, but now we have managed to make out the individual dancers.”

Addadi points out that isolated podosomes look, from above, like a tent with rope-like lines radiating from a central pole. “In effect,” she says, “the podosomes may be more than just seals. They appear to act as highly connected nodes of communication between the inside and outside of the cell, enabling the cell to adjust its activity according to the condition of the bone underneath.”

Doubly Safe Activation
"Dual key” activation, in which two people must act in concert to launch a weapon, is often installed to safeguard highly destructive arms. New research at the Weizmann Institute of Science shows that cells may employ this strategy as well before launching certain potent weapons of the immune system.

Interferons, which were discovered 50 years ago, are the body’s first line of defense against viral attack. They are produced in cells that have been invaded by viruses, and from there, they spread out to warn other cells to prepare for the impending onslaught. These signaling molecules are associated with the symptoms fever and inflammation of viral infections such as the flu. Three main interferon families have been identified, and they are known by the Greek letters alpha, beta and gamma. Interferons alpha and beta are very similar: They have nearly identical modes of action and even attach to the same receptor on the cell wall. Interferon gamma is different from these two. It has its own receptor and, in addition to its immediate antiviral actions, is involved in a number of crucial activities in the immune system, including a step known as antigen presenting, which enables the immune system to tailor antibodies to a specific enemy, and the activation of certain immune cells that engulf and destroy pathogens.

But new findings published recently in the Proceedings of the National Academy of Sciences (PNAS), show that the third type of interferon often doesn’t act alone. The Weizmann Institute team headed by Prof. Menachem Rubinstein of the Molecular Genetics Department, which included Dr. Vladimir Hurgin, Dr. Daniela Novick and Dr. Ariel Werman, together with Prof. Charles Dinarello of the University of Colorado, USA, found that another molecule that’s produced inside cells, interleukin 1- alpha (IL-1 alpha), must be present for initiating many of the basic activities of interferon gamma.

While molecules have been known to work together in this way, the collaboration between interferon gamma and IL-1 alpha came as something of a surprise to scientists: Although the molecules are produced in two independent systems, they match like two halves of a key: IL-1 alpha doesn’t affect alpha or beta interferons, and interferon gamma seems to work specifically with IL-1 alpha. They were also surprised because interferons, which form the basis of a number of drugs (mainly alpha and beta), have been widely studied, yet the connection between these two molecules had not been seen before. Rubinstein’s explanation is that previous interferon experiments had been performed with cells that produced their own IL-1 alpha in the lab culture, and thus scientists had missed its effect.

Interferon gamma and IL-1 alpha have a synergistic effect on each other, activating around 500 genes, including those that bring about the fever and muscle aches. Rubinstein: “The antiviral activity of interferon gamma comes at a high cost. We think this is the reason the body uses a ‘dual key’ system to provide an extra level of security before paying that price.”

One Membrane, Many Frequencies
Modern hearing aids, though quite sophisticated, still do not faithfully reproduce sound as hearing people hear it. New findings at the Weizmann Institute of Science shed light on a crucial mechanism for discerning different sound frequencies and thus may have implications for the design of better hearing aids.

Research by Dr. Itay Rousso of the Weizmann Institute’s Structural Biology Department, which recently appeared in the Proceedings of the National Academy of Sciences (PNAS), suggests that a thin structure in the inner ear called the tectorial membrane responds to different frequencies. This membrane communicates between the outer hair cells which amplify sound in the form of mechanical vibrations and the inner hair cells which convert these mechanical vibrations to electrical signals and pass them on to the brain via the auditory nerve. If certain genes for this membrane are missing or damaged, total deafness ensues.

Rousso and research student Rachel Gueta, together with researchers at the Ben-Gurion University of the Negev, wanted to explore the mechanical properties of the tectorial membrane. Using an atomic force microscope, which probes surfaces with a fine microscopic needle, they tested the resistance of the  gel-like membrane at various points to assess precisely how rigid or flexible it was. To their surprise, the scientists found that the level of rigidity varies significantly along the length of the membrane: One end of the membrane can be up to ten times more rigid than the other.

These differences occur in the part of the membrane that is in direct contact with the outer hair cells. Observation under a scanning electron microscope revealed that this variation is due to changes in the way the protein fibers are arranged: At one end, they form a flimsy, net-like structure that allows the membrane to be flexible; on the rigid side the fibers are densely and uniformly packed.

The more rigid a tectorial membrane is, the higher the frequency at which it can vibrate. Thus, the flexible end of the membrane, which should respond to low-frequency vibration, is found near the hair cells that transmit low frequencies, and the rigid end near hair cells that transmit high ones. This spatial separation, say the scientists, translates into the ability to distinguish between sounds of different frequencies.

The new understanding of the mechanics of hearing may assist in the development of better hearing aids. Rousso, meanwhile, plans to continue exploring how variations in membrane rigidity affect hearing. He intends to test tectorial membranes under different physiological conditions to further understand how we hear such a wide range of frequencies (the highest is a thousand times the lowest), as well as to shed light on the causes of certain hearing problems.

It’s Only a Game of Chance
The validity of a leading theory that has held a glimmer of hope for unraveling the intricacies of the brain has just been called into question. Dr. Ilan Lampl of the Weizmann Institute of Science’s Neurobiology Department has produced convincing evidence to the contrary. His findings recently appeared in the journal Neuron.

Cells in the central nervous system tend to communicate with each other via a wave of electrical signals that travel along neurons. The question is: How does the brain translate this information to allow us to perceive and understand the world before us?

It is widely believed that these electrical signals generate spiked patterns that encode different types of cognitive information. According to the theory, the brain is able to discriminate between, say, a chair and a table because each of them will generate a distinct sequence of patterns within the neural system that the brain then interprets. Upon repeated presentation of that object, its pattern is reproduced in a precise and controlled manner. Previous experiments had demonstrated repeating patterns lasting up to one second in duration.

But when Lampl and his colleagues recorded the activity of neurons in the brain region known as the cortex in anaesthetized rats and analyzed the data, they found no difference in the number of patterns produced or the time it takes for various patterns to repeat themselves, compared with data that was randomized. They therefore concluded that the patterns observed could not be due to the deterministically controlled mechanisms posited in the theory, but occur purely by chance.

The consequence of this research is likely to contribute significantly to the ongoing debate on neuronal coding. Lampl: “Since the 1980’s, many neuroscientists believed they possessed the key for finally beginning to understand the workings of the brain. But we have provided strong evidence to suggest that the brain may not encode information using precise patterns of activity.”

According to the study’s findings, which appeared today in Nature Genetics online, aberrations in the activities of these genes are tied to certain types of cancer, as well as to the relative aggressiveness of the cancer. These insights may, in the future, lead to the development of ways to restore the brakes on runaway cell division and halt the progression of cancer.

First, the scientists mapped the network of genes that is activated in normal cells upon receiving the order to divide. The “divide!” signal comes from outside the cell in the form of a chemical called a growth factor, and it initiates a chain of events inside the cell. The genes activated in this sequence produce proteins, some of which cause cell division and others that put the brakes on that division. To find which genes were responsible, the scientists needed to sift through a huge quantity of data on genes and their activities. To cope with this monumental task, a team of Weizmann Institute researchers from diverse fields pooled their knowledge and experience: Prof. Yosef Yarden of the Biological Regulation Department, Prof. Eytan Domany of the Physics of Complex Systems Department, Prof. Uri Alon of the Molecular Cell Biology Department, and Dr. Eran Segal of the Computer Science and Applied Mathematics Department. Working with them were Prof. Gideon Rechavi of the Sheba Medical Center and researchers from the M.D. Anderson Cancer Center in Houston, Texas, headed by Prof. Gordon B. Mills.

This collaboration between physicists, mathematicians, computer scientists, and biologists the sort of multidisciplinary research for which the Weizmann Institute has gained a global reputation yielded some startling results. They found that following the receipt of the growth factor signal, cell activity takes place in a number of separate waves in which genes are turned on and off for different periods of time. In the first wave, the activity of a few genes rises for about 20 to 40 minutes. These are the genes that cause the cell to divide. In contrast, the next four waves, ranging from 40 to 240 minutes after the signal, are comprised primarily of gene activity tied to the process of halting cell division.

The scientists then focused on identifying the genes in these later waves and confirming that they do, indeed, put the brakes on cell division. Through their wide-ranging study, they found 50 genes that interfere with the genetic activities of the first wave. This braking system works by producing proteins that directly attach to the cell-division genes, hindering their activity. Yet another protein they identified works, instead, by dismantling messenger RNA carrying instructions for making cell division proteins from the genes to the cell’s protein-production machinery.

In tests conducted on tissues from ovarian cancer patients, the scientists found a correlation between levels of activity in the “braking” genes, rates of survival, and the aggressiveness of the disease. These findings point the way toward the development of a personal genetic profile that might pinpoint the genetic defects responsible for each cancer and help doctors tailor a treatment fitted to each patient. Such a genetic profile can also help predict the individual progression of the disease. In the future, the identification of the exact factors causing uncontrolled cell division in different cancers might lead to the development of effective treatments for preventing or halting cancer growth.

Also participating in the research were research students Ido Amit, Ami Citri, Gabi Tarcic, and Menachem Katz of the Biological Regulation Department, and Tal Shay of the Physics of Complex Systems Department.

Livneh’s research deals with repair mechanisms for DNA, the material of genes. Cells maintain sophisticated repair systems to prevent the accumulation of mutations that might lead to cancer. In these systems, molecular detectors scan the DNA for injury. A sort of local operation is then performed to cut out and dispose of the damaged segment and replace it with a new one.

In their study, which appeared in Cancer Research, the scientists asked whether a reduced individual ability (non-inherited) to repair DNA damage increases chances of getting head and neck cancer. Smoking damages DNA and is known to be a major cause of this disease, which can affect the throat, mouth and larynx. The researchers focused on a DNA repair enzyme called OGG1, for which they had previously developed a blood test to measure activity levels. By comparing OGG activity in healthy people with those in head and neck cancer patients, the research team found that the test was able to single out those with a heightened risk of this type of cancer: Weak levels were correlated with greater risk. According to Prof. Livneh, a smoker with low OGG activity is 70 times more likely to develop head and neck cancer than a non-smoker with normal OGG levels.

These findings join a previous study by the group in which they found that low OGG activity is an indicator of elevated risk for lung cancer, a disease also caused by smoking. Together, these studies show that a combination of low OGG activity and smoking can skyrocket a person’s chances of becoming ill with a smoking-related cancer. Also participating in the study were Dalia Elinger of the Biological Chemistry Department, Dr. Akiva Vexler of Tel Aviv-Sourasky Medical Center, Profs. Adi Shani and Alain Berrebi of Kaplan Medical Center, and Dr. Meir Krupsky of Sheba Medical Center.

The OGG blood test might be used, in the future, to identify those most at risk for lung and head and neck cancers, hopefully giving added incentive to those with the risk factor to quit smoking. In addition, drugs might be developed to reduce this risk, similar to those prescribed today to reduce the risk of heart disease. 

Complex Channels: Weizmann Institute scientists discover how ion channels are organized to effectively control nerve cell communication

The messages passed in a neuronal network can target something like 100 billion nerve cells in the brain alone. These, in turn communicate with millions of other cells and organs in the body. How, then, do whole cascades of events trigger responses that are highly specific, quick and precisely timed? A team at the Weizmann Institute of Science has now shed light on this mysterious mechanism. Their discovery could have important implications for the future development of drugs for epilepsy and other nervous system diseases. These findings were recently published in the journal Neuron.

The secret is in the control over electrical signals generated by cells. These signals depend on ion channels membrane proteins found in excitable cells, such as nerve cells that allow them to generate electrical signals, depending on whether the channels are opened or closed. Prof. Eitan Reuveny, together with Ph.D. students Inbal Riven and Shachar Iwanir of the Weizmann Institute’s Biological Chemistry Department, studied channels that work on potassium ions and are coupled to a protein called the G protein, which when activated, causes the channel to open. Opening the channel inhibits the conductance of electrical signals, a fact that might be relevant, for example, in the control of seizures.

The G protein itself is activated by another protein, a receptor, which gets its cue to carry out its task from chemical messengers known as neurotransmitters. But neurotransmitters are general messengers they can inhibit as well as excite, and the receptors can respond to either message. How, the scientists wanted to know, is the G protein targeted so quickly and precisely to activate the channel?

Reuveny and his team found that the receptor and G protein are physically bound together in a complex, allowing the process to be finely tuned. When the receptor receives a chemical message from the neurotransmitter, it is already hooked up to the correct G protein. After being activated by the receptor, the G protein changes shape, opening the ion channel. The evidence for this complex structure came from special technique called FRET (Fluorescence Resonance Energy Transfer) that can measure the distance between two molecules. The scientists observed that even without stimulation, there is a lot of energy transfer between the G protein and the potassium channel, suggesting that they are very close together.

Mutations in ion channels are likely to be involved in epilepsy, chronic pain, neurodegenerative diseases and muscular diseases, and ion channels are the target of many drugs. Understanding the basic biological phenomena behind the way proteins organize themselves and orchestrate biological processes may allow scientists to design better or more efficient drugs. 

Weizmann Institute scientists create: The First Molecular Keypad Lock

Keypad locks, such as those for preventing auto theft, allow an action to take place only when the right password is entered: a series of numbers punched in a pre-set sequence. Now, a team of scientists at the Weizmann Institute of Science has created a molecule that can function as an ultra-miniaturized version of a keypad locking mechanism. Their work appeared in the Journal of the American Chemical Society (JACS).

The molecule, synthesized in the lab of Prof. Abraham Shanzer of the Organic Chemistry Department, is composed of two smaller linked units fluorescent probes separated by a molecular chain to which iron can bind. One of these probes can shine bright fluorescent blue and the other fluorescent green, but only if the surrounding conditions are right. These conditions are the keypad inputs: Rather than the electric pulses of an electronic keypad, they consist of iron ions, acids, bases, and ultraviolet light.

Shanzer and his group, which includes Drs. David Margulies, Galina Melman and Clifford Felder, have demonstrated in the past that such molecules can be used as logic gates, such as those that form the basis of computer operations. As opposed to electronic logic gates, in which electrical switches flip ON and OFF, the team’s molecules, with various combinations of chemical and light inputs, can switch between colors and light intensities to perform arithmetic calculations.

The challenge in creating a keypad lock was in generating sequences that can be distinguished one from another. Entering the sequence 2+3+4 will yield the same result as 3+4+2 on a calculator, but a keypad lock set to one password (234) won’t open for the other (342). The scientists found that by controlling the opening rate of the logic gate within the reaction time frame, they were able to produce different, distinguishable outputs, depending on the input order. By adding light energy, which also influences the molecules’ glow, they were able to produce a molecule-size device that lights up only when the correct chemical ‘passwords’ are introduced. “It’s just like a tiny ATM banking machine,” says Shanzer.

Although these minuscule keypads are not likely to become a practical alternative to today’s anti-theft devices, Shanzer believes this example of a molecular keypad lock the first of its kind will lead to new ideas and inventions in other areas such as information security and even medicine. “Faster and more powerful molecular locks could serve as the smallest ID tags, providing the ultimate defense against forgery.” In the future, molecular keypads might prove valuable, as well, in designing ‘smart’ diagnostic equipment to detect the release of biological molecules or changes in conditions that indicate disease. 

A new method for ridding the brain of excess glutamate has been developed at the Weizmann Institute of Science.  This method takes a completely new approach to the problem, compared with previous attempts based on drugs that must enter the brain to prevent the deleterious action of glutamate.  Many drugs, however, can’t cross the blood-brain barrier into the brain, while other promising treatments have proved ineffective in clinical trials.  Prof. Vivian Teichberg, of the Institute’s Neurobiology Department, working together with Prof. Yoram Shapira and Dr. Alexander Zlotnik of the Soroka Medical Center and Ben Gurion University of the Negev, has shown that in rats, an enzyme in the blood can be activated to “mop up” toxic glutamate spills in the brain and prevent much of the damage.  This method may soon be entering clinical trials to see if it can do the same for humans.

Though the brain has its own means of recycling glutamate, injury causes the system to malfunction, leading to glutamate build up.  Prof. Teichberg reasoned that this problem could be circumvented by passing glutamate from the fluid surrounding brain cells into the bloodstream.  But first, he had to have a clear understanding of the mechanism for moving glutamate from the brain to the blood.  Glutamate concentrations are several times higher in the blood than in the brain, and the body must be able to pump the chemical “upstream.” Glutamate pumps, called transporters, are found on the outsides of blood vessels, on cells that come into contact with the brain. These collect glutamate, creating small zones of high concentration from which the glutamate can then be released into the bloodstream.

Basic chemistry told him that he could affect the transporter activity by tweaking glutamate levels in the blood.  When blood levels are low, the greater difference in concentrations causes the brain to release more glutamate into the bloodstream.  He uses an enzyme called GOT that is normally present in blood to bind glutamate chemically and inactivate it, effectively lowering levels in the blood and kicking transporter activity into high gear.  In their experiments, Teichberg and his colleagues used this method to scavenge blood glutamate in rats with simulated traumatic brain injury.  They found that glutamate cleared out of the animals’ brains effectively, and damage was prevented.

Yeda, the technology transfer arm of the Weizmann Institute, now holds a patent for this method, and a new company based on this patent, called “Braintact Ltd.” has been set up in Kiryat Shmona in northern Israel and is currently operating within the framework of Meytav Technological Incubator.  The US FDA has assured the company of a fast track to approval.  If all goes well, Phase I clinical trials are planned for the near future.

The method could potentially be used to treat such acute brain insults as head traumas and stroke, and prevent brain and nerve damage from bacterial meningitis or nerve gas.  It may also have an impact on chronic diseases such as glaucoma, amyotrophic lateral sclerosis (ALS) or HIV dementia.  Teichberg: “Our method may work where others have failed, because rather than temporarily blocking the glutamate’s toxic action with drugs inside the brain, it clears the chemical away from the brain into the blood, where it can’t do harm anymore.”

Prof. Yonath will receive the 2006-2007 chemistry prize in May, along with Prof. George Feher, a physicist at the University of California, San Diego.  The two scientists will share the $100,000 prize granted by the Wolf Foundation in Israel.

Prof. Yonath is the first scientist to determine the structure of the ribosome, the large protein-synthesis machinery of living cells.

In its official announcement, the Wolf Foundation said, “The recent emergence of ribosome structures in the crystallographic community is mainly due to Ada Yonath, who uniquely and single-handedly pioneered ribosomal crystallography over more than two decades ago, when others could not even conceive its possibility. By pushing crystallography to its limits, she demonstrated the feasibility of ribosomal crystallography, thus inspiring prominent groups to repeat her experiments. Throughout, she has been the leading force in all stages of structure determination and has introduced fundamental methodological innovations that have greatly impacted the entire field of structural biology.”

Prof. Yonath received her Ph.D. from the Weizmann Institute in 1968.  After a postdoctoral fellowship at MIT, Prof. Yonath returned to the Weizmann Institute and began her investigation into the structure of the ribosome.  “Her work paves the way to deal with the crucial issue of drug activity and resistance mechanisms, thus touching on a central problem in medicine,” the foundation said.

Prof. Yonath is The Martin S. and Helen Kimmel Professor of Structural Biology and Director of The Helen and Milton A. Kimmelman Center for Biomolecular Structure and Assembly at the Weizmann Institute.

The Wolf Prize has been awarded annually since 1978 “to promote science and art for the benefit of mankind.”

It has been known for more than a decade that the Amazon rainforest depends for its existence on a supply of minerals washed off by rain from the soil in the Sahara and blown across the Atlantic by dust. By combining various types of satellite data, Dr. Koren and colleagues from Israel, the United Kingdom, the United States and Brazil have now for the first time managed to obtain quantitative information about the weight of this dust. Analyses of dust quantities were performed near the Bodele valley itself, on the shore of the Atlantic and at an additional spot above the ocean.

The data revealed that some 56 percent of the dust reaching the Amazon forest originates in the Bodele valley. They also showed that a total of some 50 million tons of dust make their way from Africa to the Amazon region every year, a much higher figure than the previous estimates of 13 million tons. The new estimate matches the calculations on the quantity of dust needed to supply the vital minerals for the continued existence of the Amazon rainforest.

The researchers suggest that the Bodele valley is such an important source of dust due to its shape and geographic features: it is flanked on both sides by enormous basalt mountain ridges, which create a cone-shaped crater with a narrow opening in the north-east. Winds that 'drain' into the valley focus on this funnel-like opening similarly to the way light is focused by an optical lens, creating a large wind tunnel of sorts. As a result, gusts of surface wind that are accelerated and focused in the tunnel lift the dust from the ground and blow it toward the ocean, allowing the Bodele valley to export the vast amount of dust that makes a life-sustaining contribution to the Amazon rainforest.

The Weizmann Institute of Science is a renowned center of science and technology research and graduate study.  Virtually every discipline of science is represented on its campus, and an interdisciplinary approach to scientific problems is encouraged.  Its current brain-related research holds promise for understanding and treating ailments as diverse as psychological trauma, autism, schizophrenia, and Alzheimer’s disease.  Its scientific leaders are pleased to share this exchange with NYU, one of the largest private universities in the U.S., and home to the NYU Center for Neural Science.

The moderators for the forum will be Prof. Yadin Dudai, incumbent of the Sara and Michael Sela Chair of Neurobiology at the Weizmann Institute; and Tony Movshon, Silver Professor of Neural Science and Psychology at NYU.  Full presentations will be offered by Prof. Dudai and Prof. Rafael Malach of the Weizmann Institute; and Profs. David Heeger and Joseph LeDoux of NYU.

In his presentation titled “The Hidden Life of Memories,” Prof. Yadin Dudai will describe what his research has revealed about how the brain acquires sensory impressions and consolidates them into long-term memories, and how these memories can be altered or lost.  Prof. Dudai has been a Global Distinguished Professor of Neural Science at NYU since 2004.  He has held various posts in public life, including Advisor on Science Policy to Israel’s National Council for Research and Development.

Prof. Rafael Malach’s research focuses on how the human brain processes sensory information.  His presentation, titled “Watching Brains Watching Movies,” will describe how he uses state-of-the-art functional magnetic resonance imaging equipment to study brain activity patterns while subjects view motion pictures.  The findings, which reveal highly consistent patterns among normal subjects, could provide a promising tool for a better understanding of brain deficits such as autism, retardation, and dyslexia.  Prof. Malach has been on the faculty of the Weizmann Institute since 1985, and is the incumbent of its Barbara and Morris Levinson Chair in Brain Research.

In his presentation titled “Brain Imaging: A New Window into the Human Mind,” David Heeger, Prof. of Psychology and Neural Science at NYU, will discuss how he uses functional magnetic resonance imaging to investigate the relationship between the brain and behavior.  His work spans the fields of engineering, psychology, and neuroscience.  Its interdisciplinary nature is reflected in the array of honors Prof. Heeger has received, including the David Marr Prize in computer vision; an Alfred P. Sloan Research Fellowship in neuroscience; and the Troland Award in psychology from the National Academy of Sciences.

The groundbreaking research of NYU’s Prof. Joseph LeDoux focuses on the brain mechanisms of emotion and memory.  In addition to articles in scholarly journals, he is the author of two highly-regarded books for the general public, The Emotional Brain: The Mysterious Underpinnings of the Emotional Life and Synaptic Self: How Our Brains Become Who We Are.  His work involves fascinating case studies, and suggests new directions for research in the biology of mental illness.  Prof. LeDoux’s presentation is titled “The Emotional Brain: Friend and Foe.”  He joined NYU in 1989, and is currently the Henry and Lucy Moses Professor of Science in Neural Science and Psychology.

More information about this event can be obtained by contacting Eileen Radway at (212) 895-7953 or eileen@acwis.org.

The solar project is the result of collaboration between scientists from the Weizmann Institute of Science, the Swiss Federal Institute of Technology, Paul Scherrer Institute in Switzerland, Institut de Science et de Genie des Materiaux et Procedes - Centre National de la Recherche Scientifique in France, and the ScanArc Plasma Technologies AB in Sweden. The project is supported by the European Union's FP5 program.

Hydrogen, the most plentiful element in the universe, is an attractive candidate for becoming a pollution-free fuel of the future. However, nearly all hydrogen used today is produced by means of expensive processes that require combustion of polluting fossil fuels. Moreover, storing and transporting hydrogen is extremely difficult and costly.

The new solar technology tackles these problems by creating an easily storable intermediate energy source form from metal ore, such as zinc oxide. With the help of concentrated sunlight, the ore is heated to about 1,200°C in a solar reactor in the presence of wood charcoal. The process splits the ore, releasing oxygen and creating gaseous zinc, which is then condensed to a powder. Zinc powder can later be reacted with water, yielding hydrogen, to be used as fuel, and zinc oxide, which is recycled back to zinc in the solar plant. In recent experiments, the 300-kilowatt installation produced 45 kilograms of zinc powder from zinc oxide in one hour, exceeding projected goals.

The process generates no pollution, and the resultant zinc can be easily stored and transported, and converted to hydrogen on demand. In addition, the zinc can be used directly, for example, in zinc-air batteries, which serve as efficient converters of chemical to electrical energy. Thus, the method offers a way of storing solar energy in chemical form and releasing it as needed.

'After many years of basic research, we are pleased to see the scientific principles developed at the Institute validated by technological development,' said Prof. Jacob Karni, Head of the Center for Energy Research at Weizmann.
'The success of our recent experiments brings the approach closer to industrial use,' says engineer Michael Epstein, project leader at the Weizmann Institute.

The concept of splitting metal ores with the help of sunlight has been under development over the course of several years at the Weizmann Institute's Canadian Institute for the Energies and Applied Research, one of the most sophisticated solar research facilities in the world, which has a solar tower, a field of 64 mirrors and unique beam-down optics. The process was tested originally on a scale of several kilowatts; it has been scaled up to 300 kilowatt in collaboration with the European researchers.

Weizmann scientists are currently investigating metal ores other than zinc oxide, as well as additional materials that may be used for efficient conversion of sunlight into storable energy.

The meeting, entitled "A Herbicide-Resistant Maize Method for Striga Control: A Meeting to Explore the Commercial Possibilities," will demonstrate the results of the new technology in the field, present the current status of this herbicide-resistant maize technology, assess its commercial and regulatory aspects, and evaluate its future. The meeting is designed to expose interested parties in the public and private sectors to a powerful new weapon that could dramatically alleviate the Striga scourge.

At the UN-sponsored World Food Summit in Rome (June 10-13), UN Secretary General Kofi Annan stated that "as many as 24,000 people a day die" of starvation around the world. This devastation is substantially concentrated in Africa. A major contributor to the problem is Striga hermonthica, or witchweed, a parasitic weed that ravages grain crops in several parts of the world--particularly in sub-Saharan Africa, where the weed infests approximately 2040 million hectares of farmland cultivated by poor farmers and is responsible for lost yields valued at approximately $1 billion annually. An estimated 100 million farmers lose from 20% to 80% of their yields to this parasite. In Kenya alone it severely infests 150,000 hectares of land (76% of the farmland in Western Kenya), causing an estimated annual crop loss valued at $38 million.    

The weed thrives by attaching itself, hypodermic-like, to the roots of a suitable host crop. It sends up a signal that says "feed me," and not only sucks up the crop's energy but also competes for much of its nutrients and water, while poisoning the crop with toxins and stunting its growth.    

Until now, other methods to control this parasitic weed have been long-term and often impractical and, hence, have not been widely adopted by farmers. African farmers commonly remove the witchweed by hand, but by the time it emerges above-ground, it has already drained the crop and done its damage. Herbicides, applied during that same post-emergence period, are also ineffective for the same reason.

Prof. Jonathan Gressel of the Weizmann Institute's Department of Plant Sciences proposed an innovative solution to the parasitic weed problem that relies on a new use for a certain type of corn that was developed, using biotechnology, in the United States. The corn carries a mutant gene that confers resistance to a specific herbicide, leaving the corn plant unharmed when treated with this herbicide. As an alternative to spraying entire fields, Prof. Gressel suggested that herbicide-resistant seeds be coated with the herbicide before planting. Once the crop's plants sprout from the seeds, the parasites unwittingly devour the weed-killing chemical from the crop roots or surrounding soil and die. By the time a crop ripens, the herbicide, applied in this way at less than 1/10th the normal rate, has disappeared, leaving the food product unaffected.

Dr. Fred Kanampiu, a CIMMYT scientist based in Kenya, has tested this approach for more than ten crop seasons while CIMMYT breeders crossed the gene into African corn to produce high-yielding varieties that are resistant to major African diseases, as well as to the herbicide. Witchweed was virtually eliminated in plots planted with herbicide-coated seeds, as will be shown at the Kisumu meeting. The experiments indicate that a low-dose herbicide seed coating on resistant corn can increase yields up to four-fold in fields highly infested with witchweed. The herbicide is coated on the seed together with the fungicide-insecticide mix that is normally used in Africa to provide healthy plants. With this technology the farmer does not have to purchase spray equipment and can continue interplanting legumes between the corn plants a common practice among smallholder African farmers.  

This research was supported in part by the Canadian International Development Agency (CIDA) through the CIMMYT East Africa Cereals Program and by the Rockefeller Foundation. Initial herbicide-resistant corn seeds for breeding into CIMMYT varieties were provided by Pioneer International, USA.

Glaucoma, which affects 1 percent of the adult population, is the main cause of blindness in adults. The majority of patients with chronic glaucoma have increased pressure inside the eye due to defective drainage of the transparent fluid that bathes the eye and nourishes its outer cells. The increase in this intraocular pressure (IOP) damages the optic nerve, causing it to degenerate and often leading to loss of eyesight.

For many years, the search for improved glaucoma therapies focused on correcting the eye's drainage system to reduce IOP. Eventually, however, it became clear that reducing the pressure was not enough to halt the ongoing degeneration of the optic nerve and did not eliminate the risk of blindness. Scientists concluded that a crucial factor was being overlooked and they set out in search of this missing link.

Approximately five years ago, Prof. Michal Schwartz of the Weizmann Institute's Neurobiology Department proposed a new concept to account for the continuing degeneration of the optic nerve that occurs after the pressure in the eye had been reduced. Schwartz suggested that while the initial damage to the optic nerve is indeed caused by increased eye pressure, secondary factors triggered by the initial damage contribute to the nerve's ongoing degeneration. The offending factors include chemicals that play an important role in the life of a healthy nerve, but when the nerve degenerates, their concentrations increase to a toxic level. One of these chemicals is the neurotransmitter glutamate, which spills from damaged nerve cells and adversely affects healthy neighboring cells.

In line with this concept, Prof. Schwartz developed an original strategy for tackling the problem. To protect the nerve from harmful substances coming from the body itself, she recruited the immune system, whose well-known role is to defend the body against outside 'invaders.' This approach at first raised a few eyebrows, mainly because it involved cells that, when activated, usually cause one of the autoimmune diseases in which the body mistakenly attacks itself, such as juvenile diabetes or multiple sclerosis. The concept of using these 'enemy' cells to heal the body seemed uncanny.

Prof. Schwartz, who has also developed an immune-based therapy for spinal cord injuries now being tested in a clinical trial, believes that contrary to accepted wisdom autoimmunity can play a beneficial role in the body. A series of studies in her lab has shown that immunization with fragments of proteins belonging to myelin, the protective sheath of the nerves, can prevent degeneration of the damaged optic nerve. However, the use of such protein fragments, or peptides, for immunizing people is fraught with risk because some of these peptides cause the immune system to attack nerve fibers, leading to multiple sclerosis. Since humans vary greatly in their genetic makeup, it is difficult to establish which of the peptides would cause disease in a specific patient.

Looking for a safe alternative to these peptides, Schwartz and her group, in collaboration with Profs. Irun Cohen and Michael Sela of the Weizmann Institute's Immunology Department, demonstrated that immunization with Copaxone, a synthetic compound that reacts with cells that respond to self-proteins, protects the damaged optic nerve from neuronal degeneration. Copaxone was developed at the Institute by Dr. Dvora Teitelbaum, Prof. Ruth Arnon and Prof. Michael Sela as a drug for multiple sclerosis.

In the present study, the scientists sought to establish how Copaxone produces its protective effect on the nerve. This research -- conducted by Prof. Schwartz, Dr. Eti Yoles and graduate students Jonathan Kipnis and Hadas Schori -- showed that immunization with Copaxone shields the nerve from the toxic effects of the neurotransmitter glutamate. These findings strongly suggest that Copaxone immunization is a potential therapy for glaucoma, in which the optic nerve undergoes degeneration and glutamate levels rise. Indeed, in another series of experiments conducted together with scientists from the U.S. company Allergan, Inc. (who developed the rat model that simulates chronic glaucoma), Copaxone immunization proved even more effective. In rats immunized with a single injection of Copaxone, only about 4 percent of nerve cells died in the glaucoma-affected eye, compared with 28 percent in rats that were not immunized. Thus, immunization with Copaxone dramatically protected the nerve from pressure-induced death.

Following the success of this research, trials in human patients with glaucoma are expected to begin soon. Scientists hope that the trials will be facilitated by the fact that the U.S. Food and Drug Administration has already approved Copaxone.

While prior studies had already demonstrated that adding acetlycholine to neuronal junctions during learning affects information reception and storage, subsequent testing of the cell's ability to retrieve the information produced inconsistent results. The findings ranged from significant or slight improvement following acetylcholine application, to the lack of any learning enhancement whatsoever.

In recent years, scientists throughout the world have tried to elucidate the reasons underlying these varying results. Now, a team of researchers headed by Drs. Ehud Ahissar of the Weizmann Institute's Department of Neurobiology and Daniel Shulz of the U.N.I.C. laboratory at the CNRS, have shown how acetylcholine is able to consistently enhance neuronal learning and information retrieval.

The secret, researchers found, is to control the level of acetylcholine at the neuronal junctions during both the 'ins' and 'outs' of information processing - specifically, during information reception and storage, as well as during its retrieval and implementation.

These findings, due to appear in the February 3rd issue of Nature, represent yet another step in unraveling the enigma of learning and memory embodied within the brain, as well as probing the causes of cognitive deficits observed in patients with Alzheimer's and other neurodegenerative diseases.

To resolve this paradox, scientists have postulated the existence of a water-based "cooling system" that regulates the temperature of interstellar clouds, enabling the contraction to continue. Now a Weizmann Institute study reported in Physical Review Letters provides experimental evidence that the billions of stars that populate our firmament indeed had a watery birth.

Researchers have theorized that water molecules in interstellar clouds exert a cooling effect by colliding with the gas particles and absorbing their energy that is later released in the form of radiation. But attempts to observe water in the stars using Earth-bound telescopes have always been thwarted by the presence of water particles in our planet's atmosphere. Scientists have, however, detected a similar substance that could be an intermediary product in water formation: hydronium, or H3O+, which contains three hydrogen atoms (as compared with water's two), along with one oxygen atom.

Drs. Daniel Zajfman and Oded Heber of the Weizmann Institute's Particle Physics Department have now completed an experiment demonstrating that water is indeed formed in interstellar clouds in a reaction involving hydronium. The experiment was carried out at an advanced installation called an ion storage ring at the University of Aarhus, Denmark, in collaboration with Aarhus researchers Dr. Lars Andersen, Dr. Dror Kella and Lisa Vejby- Christensen.

The scientists simulated the physical and chemical conditions in interstellar clouds and showed that water is formed there in a reaction between a charged hydronium molecule and a single electron. They also found that a permanent ratio between water and hydronium molecules is maintained in these clouds.

Special equipment aboard the U.S. research satellite SWAS, to be launched later this year, will be used to further explore the new findings without the interference of the Earth's atmosphere, in particular by directly measuring the quantity of water in the forming stars.

The finding, reported in the September issue of the Journal of Archaeological Science, is expected to shed new light on the ways primitive humans used fire, and on their lifestyles and environment. While humans are believed to have first harnessed fire at least 500,000 years ago, ash -- the most direct evidence of fire -- is hard to find and even harder to recognize, because most of the minerals in it are highly reactive and unstable, and begin changing within days of a fire's going out.

As a result, until now evidence of the use of fire has been mostly indirect, coming from blackened bones or fractured flint tools. Now Weizmann Institute's Prof. Steve Weiner -- working with post-doctoral fellow mineralogist Dr. Solveig Schiegl, archaeologist Prof. Ofer Bar-Yosef of Harvard University, and geologist Prof. Paul Goldberg of Boston University -- has traced the chemical transformations that ashes undergo over time, and has discovered that a small group of minerals remains relatively stable and can serve as a telltale sign of ash even after thousands of years.

"We know how to recognize this component now and can look for it, and we have a much better chance of proving something was ash even though it doesn't look like ash at all," says Weiner, a structural biologist who heads the Institute's Environmental Sciences and Energy Research Department.

By analyzing the ashes, scientists can learn about the circumstances in which early humans used fire, which can help explain how they lived, cooked, kept warm, and protected themselves. The ashes and surrounding sediments can also throw light on changes in climate, geology and ecology over the millennia.

"Fire is such an important part of the archaeological record that it may come as a surprise to learn that until now very little analysis has been done on something as basic as ashes," Weiner said.

Archaeologists have assumed that certain sediments are ash if they are found in the form of a hearth, but there has been little scientific analysis of the composition and microscopic structure of ash minerals.

Weiner made his discovery while studying sediments in two northern Israeli caves that had been inhabited from at least 250,000 years ago up to 40,000 years ago.

At the caves, he set up a portable laboratory that included a sophisticated infrared spectrometer, enabling him to analyze mineral samples on-site -- the first time such equipment was used at any archaeological dig. Weiner found that sediments across the floor of one cave, Hayonim, kept giving enigmatic readings on the spectrometer.

The breakthrough came after he realized he had seen the same spectrum in some hearths preserved in the other cave, Kebara.

"That gave me the connection to fire, and I realized that this reading indicated ashes," Weiner said.

To check the finding, Weiner and colleagues conducted experiments in which they burned wood from local trees. They found that the ashes contained a small, relatively stable group of minerals, known as siliceous aggregates, which make up only about 2 percent of the ash's original volume.

It was this fraction that was preserved in the caves. In fact, Weiner found that these siliceous minerals made up a large proportion of the cave sediments, which were up to 3 meters (9 ft.) thick in places -- a finding which suggested the caves had been intensively occupied over millennia.

Weiner and colleagues are now seeking to uncover the record of human habitation in the caves by analyzing the different sediment layers: They hope to distinguish between periods of occupation and non-occupation on the basis that ash would be present only in sediments from periods of occupation.

In addition, by analyzing the other minerals in the ash remnants, they are trying to obtain clues about the types of vegetation present in prehistoric times, which will yield information about the prevailing climate and ecology.

As a result of his discovery, Weiner has recently become the first Western scientist in 60 years to work at China s famous Zhoukoudian cave, home to the bones of Peking Man, believed to be among the first humans to use fire. Weiner will spend the next year analyzing samples he brought back from China in May, and trying to determine precisely what they comprise, whether there were indeed fires at the site, and whether they were lit by humans.

Weiner holds the Weizmann Institute's I.W. Abel Chair of Structural Biology and heads the Sussman Family Center for the Study of Environmental Sciences.