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.

They do this by binding to messenger RNA molecules, preventing them from carrying out protein synthesis. RNA interference, as this process is called, provides the cell with a way of controlling the levels of hundreds of different proteins by turning genes off at the appropriate times.

“Now we understand that miRNAs are important in regulating the processes inside the cell, inside the organ, and inside the organism,” says Dr. Eran Hornstein of the Weizmann Institute of Science’s Department of Molecular Genetics. “When these components are malfunctioning, you end up with a disease.”

Dr. Hornstein and his team study how miRNAs regulate the activity of genes during the development of the pancreas, bone, and cartilage, and how malfunctions may contribute to diseases.

Before joining the Institute in 2006, Dr. Hornstein received his MD/PhD from the Hebrew University–Hadassah School of Medicine in Jerusalem. He started out with the goal of becoming a physician, but was ultimately drawn to basic science research and completed his postdoctoral studies in the Department of Genetics at Harvard Medical School.

While at Harvard, he helped provide some of the earliest evidence that miRNAs play a role in vertebrate development—specifically, in the development of limbs. The study of miRNAs is so new that at the time of Dr. Hornstein’s postdoctoral research, the first miRNA had been identified only a decade earlier.

Dr. Hornstein’s current investigations include studying the role of miRNAs in diabetes. “We know now that miRNAs are highly relevant to the regulation of insulin gene expression in beta cells that are key to controlling the body’s glucose levels. And we think we also have a clue about particular miRNAs that are highly relevant to the development of diabetes in mice,” he says.

Along with his colleagues, he is also looking at the role of miRNAs in amyotrophic lateral sclerosis (ALS, or Lou Gehrig’s disease). ALS is a neurological disorder that affects motor neurons—the nerve cells in the brain and spinal cord that control muscle movements—causing muscle weakness and paralysis. “It’s a very devastating disease and the genetics of it are completely unknown, so we don’t yet know how to cure it,” says Dr. Hornstein. “But we have now developed a very nice model, in mice, to show that loss of miRNA activity may generate ALS.”

He believes this research could shed light on the role of miRNAs in other neurodegenerative conditions, such as Alzheimer’s disease. “It seems that miRNAs are extremely relevant to the functionality of neurons,” Dr. Hornstein says. He explains that mi-RNAs seem to work not at the cell nucleus, but at the periphery. Neurons sometimes need to regulate their functionality at a distance, very far away from the center of the cell. It now appears that regulatory RNAs—particularly miRNAs—might specialize in regulating cell functions at a distance from the center.

A better understanding of miRNAs, which are now thought to regulate more than a third of all human genes, could eventually be useful for the treatment of a wide range of illnesses ranging from osteoporosis to cancer. “Down the road, I hope the findings in my lab will come together with technologies that are being developed in order to generate new therapeutics for diseases,” says Dr. Hornstein.

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.

It was during those early days of her research in the laboratory of microbiologist and Nobel laureate David Baltimore that she realized, she says, “that science is one of the most exciting things one can do—you can really pursue your dreams.”

Since then, Prof. Rotter, who is head of the Weizmann Institute’s Department of Molecular Cell Biology, has devoted her career to this gene, now known as the “guardian of the genome” because it protects us from developing cancer. She was one of the first to develop antibodies against p53, along with other genetic tools, laying the foundations for the study of its function.

In its normal form, p53 plays a pivotal role in protecting cells from becoming cancerous. “The p53 is a very smart gene,” says Prof. Rotter. It can sense when cells have damaged DNA (from exposure to ultraviolet radiation or chemicals, for example) and signal them to either repair that damage or undergo a process of self-destruction. When p53 is mutated, however, it loses this function; as a result, cells carrying damaged DNA can go on dividing and eventually transform into tumor cells. Mutant forms of p53 are found in more than 60 percent of human tumors.

Although p53 is possibly the most studied gene ever—thousands of papers on it have been published—Prof. Rotter finds that some basic questions have still only been partially answered: What is the function of p53 in the normal cell? How does mutant p53 contribute to cancer development? She believes that if we can understand exactly how p53 works, we can find ways to use it to stop the proliferation of cancer cells. Ultimately, her   goal is to come up with new kinds of therapies that she describes as “made just for you and your cancer.”

She has already made progress toward this goal through her research on the possibility of tailor-made chemotherapy. Prof. Rotter and her team conducted an  experiment in which they treated cancer cells with chemotherapy. Some of the cancers died, but others were very resistant to the chemo. The researchers evaluated the status of p53 in the cancers, and found that different types of mutant p53 exhibited different levels of resistance to the therapy.

Prof. Rotter thinks it may be possible, in the future, to increase the effectiveness of cancer therapy by evaluating the specific type of mutant p53 the patient is expressing and choosing a chemotherapy drug that is suited to it. Her team is now creating a library of chemotherapy drugs targeted to various mutant forms of p53.

Since 2000, Prof. Rotter has also directed the Weizmann Institute’s Women’s Health Research Center, which promotes basic research on gender-related physiology and diseases and has supported studies of cancer, fertility, and osteoporosis. For example, several of the research groups have examined the buildup and breakdown of bone mass and described a number of enzymes that affect the balance of bone accumulation or loss. Understanding how bone degradation is regulated may help in developing better treatments for osteoporosis.

Prof. Rotter is optimistic that basic research will continue to lead to better cancer treatments. For her part, she will continue to search for new kinds of therapies that could compensate for the malfunction of tumor suppressor genes.

Her ongoing goals include designing genetic methods for coping with cancer and making our genes stronger—possibly through inserting better genes, strengthening existing genes, or fighting the bad genes. “When we find a way to design this kind of tailormade therapy,” she says, “I think we will solve the problem of cancer.”

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.