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Science Feature Articles</p>

Through the Time Tunnel

English

 Dr. Elisabetta Boaretto and Prof. Steve Weiner. Checking exposure

 

While our distant ancestors did not use a knife and fork the way we do, they had flint - a hard rock used to create tools for hunting, cooking and building. But making these tools, it turns out, was far from easy. Flint tends to crack and wither when exposed to atmospheric weathering. While know-how for producing flint existed already 2.5 million years ago, only with time did our ancestors learn how to obtain durable production materials: their secret was to dig - obtaining flint from mines rather than surface deposits - and their idea proved to be a pivotal technological advance, with important intellectual and cultural fringe benefits.


Dr. Elisabetta Boaretto of the Environmental Sciences and Energy Research Department recently traced this cultural transition.


Working with Prof. Steve Weiner, head of the Helen and Martin Kimmel Center for Archaeological Sciences, and with Prof. Micha Hass of the Particle Physics Department, Boaretto used a nuclear physics technique to determine whether flint samples from the prehistoric caves of Tabun (in the Carmel) and Qesem (near Rosh Ha’ayen) were produced from surface or underground deposits.


“When the flint (silicon dioxide) is exposed on Earth’s surface, it produces beryllium 10 through an interaction between cosmic rays and the oxygen in the silica mineral,” explains Boaretto. “If the same material is buried about two meters below the surface, this effect is reduced to a negligible level. Our assumption was that tool samples made of flint collected from surface deposits would have measurably higher Be10 levels than those derived from mined flint.”


Using the Institute’s Koffler pelletron accelerator to measure beryllium 10 concentrations, Boaretto and her colleagues found that flint samples collected from one layer of the Tabun Cave deposited about 350,000 years ago had beryllium 10 levels similar to mined material. In contrast, those found in the Qesem Cave, from about the same period, had a beryllium 10 distribution consistent with flint gathered from above ground or from shallow quarries. Were the people of Tabun pickier - i.e. more advanced - in choosing the raw material for their flint tools than their neighbors in Qesem? The data suggest so, but more research is needed.


Other scientists collaborating in this research are: Prof. Michael Paul and postdoctoral fellow Dr. Giovanni Verri of the Hebrew University and Prof. Avi Gopher and Dr. Ran Barkay of Tel Aviv University.


From Padua to Rehovot


Elisabetta Boaretto came to Israel from Padua, Italy, for her Ph.D. in physics at the Hebrew University with Prof. Michael Paul. As part of her experimental work, she used the Koffler pelletron accelerator at the WIS (which is where she met her Israeli-born husband, Dror Kella, also a physicist) to measure rare radioisotopes from ice cores in Greenland and Antarctica. The couple later pursued postdoctoral studies at Aarhus University in Denmark. They have two children, Eyal and Iris.


Prof. Weiner’s research is supported by the Helen and Martin Kimmel Center for Archaeological Sciences; the Women’s Health Research Center; the Philip M. Klutznick Fund; the Alfried Krupp von Bohlen und Halbach Foundation and Mr. George Schwartzman, Sarasota, FL. He is the incumbent of the Dr. Walter and Dr. Trude Borchardt Professorial Chair in Structural Biology.

 

 
Dr. Elisabetta Boaretto and Prof. Steve Weiner. Flint feats
Scientific Archaeology
English
Yes

DNA Computer Might Fight Cancer

English

Prof. Ehud Shapiro and his team. Future vision of medicine

Following a newsworthy debut several years ago at the Weizmann Institute, it’s once again making headlines. The world’s smallest computer - a drop of water can hold around a trillion - has now been programmed to perform actions more often associated with doctors than computers: to diagnose and treat cancer.


The computing device successfully identified signs of cancer introduced into a test tube environment, diagnosed the type of cancer and even released an appropriate drug.


Prof. Ehud Shapiro of the Departments of Computer Science and Applied Mathematics and of Biological Chemistry, his research students - Yaakov Benenson, Binyamin Gil and Uri Ben-Dor - and Dr. Rivka Adar have made a splash in the scientific community with their futuristic vision of a “doctor-in-a-cell” that might one day be able to diagnose and treat disease from within, before symptoms even appear. Their study recently appeared in Nature and was presented at the prestigious “Life, a Nobel Story” symposium in Brussels.


The team programmed their computer to detect prostate cancer and one form of lung cancer. The computer evaluates four genes that become either under- or overactive once the disease sets in. The chosen genes control the expression of messenger RNA (mRNA), which carries information from the nucleus to the ribosome, the cell’s protein factory. The scientists introduced different levels of these RNA molecules into the test tube to simulate the presence or absence of cancer.


Made entirely of biological molecules, the computer has three components - input, computation and output. The first consists of short strands of DNA, called transition molecules, which check for the presence of the mRNA produced by each of the four cancer genes. The second component is a computation (diagnostic) unit, consisting of a long hairpin-shaped DNA strand. As the computer’s input segments check for the presence or absence of the four cancer markers, this diagnostic unit checks each input in turn, producing a positive diagnosis of malignancy only if all four markers point to cancer.


This second component also contains the computer’s third component: a single-stranded DNA known to interfere with the cancer cell’s activities. In the case of a positive diagnosis, the unit releases its hold on the therapeutic unit, activating its cancer-fighting potential.


But there’s an added safety feature: if the activity of even one of the four genes is normal (as determined by the test tube levels of the mRNA marker it codes for), the diagnosis is “not cancerous,” and the computer releases a different strand of the computer’s DNA that neutralizes the drug.


The original version of the bio-molecular computer (also in a test tube) was created by Shapiro and colleagues in 2001. This computer was capable of performing mathematical operations such as checking a list of zeros and ones and ascertaining whether all of the zeros precede all of the ones, or whether there is an even number of ones in the list. An improved system, which uses its input DNA molecule as its sole source of energy, was reported in 2003 and was listed in the 2004 Guinness Book of World Records as the smallest biological computing device.


Shapiro: “Our study offers a vision of the future of medicine. It is clear that it may take decades before such a system operating inside the human body becomes a reality. Nevertheless, only two years ago we predicted it would take 10 years to reach where we are today.”

cartoon: New meaning to "computer virus"

Prof. Shapiro’s research is supported by the Samuel R. Dweck Foundation; the Dolfi and Lola Ebner Center for Biomedical Research; the M.D. Moross Institute for Cancer Research; the Benjamin and Seema Pulier Charitable Foundation and the Robert Rees Fund for Applied Research.

 

 
(l-r) Uri Ben-Dor, Prof. Ehud Shapiro, Yaakov Benenson, Dr. Rivka Adar and Binyamin Gil. Doctor-in-a-cell
Life Sciences
English

Living Digitally

English

Dr. Uri Alon. Digital methods

Digital technology may well be the most significant advance of our time. But, as a team of scientists at the Weizmann Institute has shown, computers and DVD players have nothing on living cells, which have their own built-in digital systems.


Dr. Uri Alon, of the Molecular Cell Biology and Physics of Complex Systems Departments, along with team members Dr. Galit Lahav Shenhar, Nitzan Rosenfeld, Alex Sigal and Naama Geva-Zatorsky, discovered the phenomenon while investigating what is possibly the most researched protein ever - the tumor suppressor p53. Produced in the cell when DNA is damaged, p53 plays a role both in DNA repair and in a “self-destruct” command that switches on in the cell when damage is too great, preventing it from turning cancerous.


Probing the life cycle of this useful protein, the team saw, to their surprise, that p53 appears and disappears in regular, identical peaks, or pulses. This rhythmic pattern was completely at odds with previous findings suggesting that p53 is churned out in ever-increasing amounts as more damage is inflicted on the DNA. Each pulse recorded by the team involved the same amount of the protein and lasted for the same length of time (approximately five hours). When the amount of damage to DNA was increased, additional pulses ensued, but the size and duration of each remained stable. These pulses are like the tiny bits of information on a digital compact disk, which encodes sound using only two discrete possibilities: on or off. This is in contrast to analog-based technologies, which use the physical aspects of material to represent information, depicting it as changing continuously over time and space - similar to the grooves in a phonograph record, whose variations in depth generate ascending and descending tones.


“Digital technology has clear advantages over analog-based devices, in that it stands up well to a certain amount of noise and component imperfection, and is easier to manipulate. The cell may have evolved digital methods for similar reasons,” says Alon.


How did Alon and his team manage to observe this phenomenon, which literally thousands of others had missed? The answer lies in their non-conventional approach. Almost all previous studies of the dynamics of proteins like p53 have been done on material extracted from a large number of cells. Such studies give an average result over an entire cell population. In contrast, the Weizmann team decided to go after specific proteins in their natural setting, inside the walls of individual cells.


To accomplish this feat they applied a recent advance in genetic engineering, in which a segment of a jellyfish gene that encodes for bright fluorescent colors is inserted into the gene for the protein studied, thereby producing glowing protein molecules that can be easily distinguished under the microscope.


The p53 protein was colored with a cyan fluorescing marker, and MDM2 - another protein, responsible for dismantling p53 - was marked with yellow.


“The time-lapse sequence looked like a traffic light, with lights shining cyan, then yellow, then cyan. There was no mistaking that we were seeing something out of the ordinary,” says Alon.


Alon and his group plan to continue researching p53 and MDM2 in single cells, as they believe that the method may provide answers to some long-standing questions, such as how p53 mediates the switch from repair to suicide mode. Their findings are also important for others studying protein dynamics: “If we found one digital system, it’s likely there are others. We showed there are some phenomena that can be seen only by looking inside individual living cells,” says Alon.

 

Nights in the lab

 

Dr. Galit Lahav Shenhar, who created and led this project, was in charge of collecting the data using the fluorescence microscope. Because the cellular processes studied are relatively slow, the research required repeated 16-hour vigils, with cell photos taken every 15 minutes. “At that time, the system had to be refocused for each frame.


My lab partners were very supportive,” says Lahav. “Even my boyfriend (now husband), who is not a biologist, learned to work the microscope so I could get a few hours rest in the afternoon and come back to work until two or three in the morning. It was monotonous work, but the excitement of what we had discovered spurred me on. We might have thought our method was flawed, since the results were so unexpected, but Uri taught us to trust what we see, not what we expect to see.” The team now has a fully automated microscope, developed by Prof. Zvi Kam of the Molecular Cell Biology Department and computer scientist Yuvalal Liron, making the new generation of experiments much easier to perform.


Dr. Alon’s research is supported by the Charpak-Vered Visiting Fellowship, Canada; the Clore Center for Biological Physics; the Yad Abraham Research Center for Cancer Diagnostics and Therapy; the Estate of Ernst and Anni Deutsch, Lichtenstein; the Leon and Gina Fromer Philanthropic Fund; the Minerva Stiftung Gesellschaft fuer die Forschung m.b.H.; the James and Ilene Nathan Charitable Directed Fund; the Harry M. Ringel Memorial Foundation and Mr. and Mrs. Mordechai Segal, Israel .

 

Dr. Uri Alon. Cell circuits
Life Sciences
English

Unlikely Brain Boosters

English

Kipnis and Schwartz. Preventing mental dysfunction

Healthy body - healthy mind” is one of those sayings often quoted to children who resist vegetables or bedtime. But there may be more truth to the saying than your parents ever suspected: A new study reveals a surprising connection between the body’s immune system and the brain.


Though the cells of the immune system patrol the entire body, waging daily battle against all sorts of threats, prevailing wisdom has held that the brain remains neutral territory, blockaded against immune cells and invaders alike - any immune cells straying into the demilitarized zone were believed to interfere with the brain’s activity. But a study by Prof. Michal Schwartz and postdoctoral fellow Dr. Jonathan Kipnis of the Neurobiology Department now challenges this widely held viewpoint, shedding new light on the role of the immune system and its part in maintaining healthy brain function. Their study appeared in the Proceedings of the National Academy of Sciences (PNAS), USA.


Schwartz and Kipnis, who were joined by Dr. Hagit Cohen of Ben-Gurion University of the Negev, tested how mice bred for faulty immune systems performed when challenged to find a hidden platform in a pool of water. While normal mice learned to swim the shortest route in a matter of days, the immunity-challenged mice took much longer. But when the missing immune cells were injected into these mice, their learning curves jumped into the normal range.


Having demonstrated a possible role for immune cells in normal brain functioning, the team asked whether the immune system might also hold the key to mental disorders characterized by imbalanced brain activity. They theorized that the supply of immune cells in the brain in such diseases is either insufficient or subject to malfunction. If so, an immune system boost might be enough to overcome the impairment.


For this experiment, the scientists gave normal mice an amphetamine drug that mimics the effects of mental dysfunction in the brain. They then administered the drug Cop-1, which appears to act as a broad vaccine for the whole immune system. The group that did not receive Cop-1 vaccination exhibited disturbed, irrational behavior during the learning test, whereas the vaccinated mice behaved much like normal ones, learning to swim for the platform without any symptoms of mental dysfunction.


“There’s a seemingly logical connection,” says Schwartz. “Age- and AIDS-related dementias, for instance, might be tied to the decline in immune function. Our most important finding is that the brain does not operate independently of the rest of the body’s systems; rather, the immune system plays a pivotal role in its performance.”


Because the study impacts on several areas of higher brain function, including learning, emotions and mental stability, it might have important implications for different fields of neuromedical research. Further studies based on these findings may one day yield vaccines to prevent or treat such diseases as schizophrenia, post-traumatic stress disorder and dementias.

 

 

The dopamine tightrope walk


Immunity is a tricky balancing act. Too much, and autoimmune diseases such as diabetes or multiple sclerosis can result. Too little, however, has been shown to be tied to tumor growth and nervous system degeneration. To ensure that the autoimmune T cells will help without hurting, a second set of cells, called regulatory T cells (T-reg), work to keep them in check.


But what regulates the regulators? For some time, scientists have searched for an answer. Schwartz, Kipnis and members of their lab team have now proposed that the key to immune control may lie in the brain. In recently published research, they showed that dopamine - a pivotal chemical messenger more commonly known to be involved in movement, feelings and emotions - provides a direct line of communication to the regulators. It controls T-reg cell activity, ultimately allowing the autoimmune T cells to function upon need without the risk of developing autoimmune disease.


Indeed, research by others has provided tantalizing hints that dopamine imbalances may affect immunity: high dopamine levels have been linked to reduced tumor and neurodegenerative conditions, whereas dopamine deficiency increases the rates of these diseases, while reducing autoimmune pathologies.


Prof. Schwartz’s research is supported by the Nella and Leon Benoziyo Center for Neurosciences; the Alan T. Brown Foundation to Cure Paralysis; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Glaucoma Research Foundation; the Daniel Heumann Fund for Spinal Cord Research; Mr. and Mrs. Irwin Green, Boca Raton, FL; and Mr. and Mrs. Richard D. Siegal, New York, NY. She is the incumbent of the Maurice and Ilse Katz Professorial Chair of Neuroimmunolgy.

 

Dr. Jonathan Kipnis and Prof. Michal Schwartz. The immune connection
Life Sciences
English

Peeking Back in Time

English


May God bless and keep you always

May your wishes all come true

May you always do for others

And let others do for you.

May you build a ladder to the stars

And climb on every rung

May you stay forever young

Forever young, forever young

May you stay forever young.

-- Forever Young.  Music and lyrics: Bob Dylan

 

Prof. Shaul Hanany. Research balloons

Will the universe - born, according to the widely accepted theory, some 15 billion years ago in the Big Bang - end with a whimper? Prof. Shaul Hanany, currently of the University of Minnesota and soon to join Weizmann’s Particle Physics Department, hopes to shed light on this question by measuring cosmic microwave background radiation, a relic from the Big Bang.


According to the Big Bang theory, the entire visible universe, including all its matter and energy, once occupied a tiny, extremely hot and dense region. At some stage, and for a yet unknown reason, this region began to expand - voila: the Big Bang. During this expansion, matter dispersed in all directions and resembled a thick primordial soup.


But how, ask cosmologists, did the current structure of the universe emerge from this primordial soup? Had the original soup been entirely uniform, clumps of matter such as the galaxies would not have formed; today’s universe would still be a continuous, uniform soup, with no galaxies, stars or, of course, humans probing its nature.


The existence of distinct clumps of matter has led cosmologists to hypothesize that different areas of the primordial soup were indeed distinguished from one another by minute variations in density, much like ripples or wrinkles. With time, and under the influence of gravity, these wrinkles intensified, causing the denser areas to give rise to the galaxies and stars known today, while the less dense areas gave rise to enormous empty spaces.


This hypothesis was confirmed in April 1992, when NASA’s satellite COBE succeeded in peeking back in time to when the universe was only 300,000 years old. COBE found tiny variations in the microwave radiation arriving from different locations in the universe - providing support for the notion of differences in the density of ancient matter. The song of these ripples is that of a forever young universe. “In the very young universe, radiation was tied to matter; the two were separated only when matter dispersed and cooled down,” explains Hanany. “However, because of their common past, the differences in radiation measured today still accurately portray density differences in matter and energy way back in time.”


Some of the most precise mappings of cosmic background radiation were obtained in two experiments co-led by Hanany. The results from one of them were subsequently selected as one of the ten most important scientific discoveries of the year 2000 by the editors of Science magazine. Both experiments used research balloons - one was launched in Texas and landed there; the other was launched in Sweden and landed in Siberia.


Analyzing the data from these experiments, Hanany and his colleagues inferred the total density of matter and energy in the universe with unprecedented accuracy - a finding that led to the conclusion that space is flat. Einstein’s equations allow for both flat and curved geometries for our space. Now we know which of those is realized in nature.


Drawing on additional astrophysical data the team also calculated the densities of different types of matter and energy, showing that the “regular” matter with which we are all familiar and from which we are all made - that is, stuff made of protons, neutrons and electrons - constitutes only 5 percent of the entire matter and energy in the universe. The nature of the other 95 percent remains unclear. What we do know is that it consists of two distinct types: “dark matter” and “dark energy.” Although we can’t see the dark matter, we are able to accurately measure its gravitational pull on regular visible matter, which slows down the expansion of the universe. Dark energy, in contrast - which constitutes roughly 65 percent of the stuff in the universe - also can’t be seen, but its gravitational effect is opposite to that of both dark and regular matter. It exerts a negative, or repulsive, force of gravity, thereby speeding up the expansion of the universe.


“The large amount of dark energy tends to accelerate the universe’s rate of expansion,” Hanany says, “thereby widening the distances between galaxies at an ever-increasing rate. If this process continues for several billions of years, Earth and our galaxy, the Milky Way, will be isolated in the expanse of the universe, while all other galaxies will have flown away to enormous distances, completely disappearing from view. The universe will seem dark and bleak.”


Hanany and his colleagues are currently focusing on the polarization of cosmic background radiation, hoping to obtain more information about the universe as it was a split second after the Big Bang. “It will be a fantastic sight - viewing the universe so close to its birth,” he says.

 

A montage image of the cosmic microwave background radiation obtained in 2003 by NASA’s WMAP satellite and from two earlier experiments co-led by Prof. Hanany: Maxima, performed in 2000 (square) and Archeops, 2002 (region above upper black line). The WMAP results agree with both the Maxima and Archeops findings

 

 
Prof. Shaul Hanany. The end of the world as we know it
Space & Physics
English

Fighting the Flu

English

Prof. Ruth Arnon and Dr. Tamar Ben-Yedidia. multi-year vaccine

Viruses are exceptionally efficient creatures. They’re not even really “alive” in one sense, lacking a reproductive mechanism of their own. And yet they multiply so effectively - at the expense of their host cells - that they often kill in the process.


It’s a sneaky business, based on a key-fits-locks mechanism. The virus first anchors onto its host, whereupon a protein in its envelope attaches to a fitting receptor on the cell membrane. Having gained access to the cell’s headquarters - its nucleus - the virus incorporates its genetic material into the host’s DNA machinery, causing it to produce hordes of the invading viral particles.


Scientists working to block viral diseases are developing vaccines aimed at preventing this initial anchoring. The accepted approach involves introducing a weakened or killed virus, which the immune system learns to recognize, generating defensive antibodies. Future encounters with a live virus will trigger a swift immune response.


But viruses don’t just sit back and take it. In a rapid evolutionary process, they frequently change their surface protein “keys,” thus evading discovery - it’s similar to an ongoing struggle between code makers and code breakers.


The flu virus, for example, changes the shape of its envelope proteins almost annually - making effective vaccines nearly useless the following year. But Prof. Ruth Arnon and Dr. Tamar Ben-Yedidia of the Institute’s Immunology Department might now change this.


The scientists focused on one of the surface proteins of the flu virus, called hemagglutinin, which consists of three molecular chains wrapped around one another like rose petals. When the virus anchors itself on a living cell, these “petals” open to reveal a previously hidden peptide, which - the scientists found to their surprise - is unvaried across a range of viral strains. In other words, while hemagglutinin frequently changes its external petal-structured envelope to avoid detection, the hidden peptide has remained conserved throughout evolution. BINGO! - a potential Achilles’ heel has been uncovered. By targeting this fixed “weak link” of the virus, the scientists reasoned, it might be possible to develop a vaccine that would deliver a long-lasting - rather than merely annual - blow.


And lab results suggest that they are right on the mark. Working with (then graduate student) Dr. Rafi Levy, Arnon introduced a molecule containing one of the hidden peptides into mice. The result: 50 percent of the vaccinated mice showed resistance to infection by a range of flu viral strains. The results were even more telling when the mice were treated with vaccines containing three different “hidden” peptides: 90 percent of them demonstrated immunity. Moreover, even seven months later, 50 percent remained protected.


Encouraged by these findings, Arnon and Ben-Yedidia started examining the immune response of mice implanted with a human immune system. They used a new vaccine consisting of four different “hidden” peptides intended to provoke an immune response in humans. Though subsequently infected with a very large, usually fatal, dose of the virus, all of the mice survived.


Following these successful studies in mice, BiondVax, a recently established start-up, now plans to continue the development of this approach and perform clinical trials in humans. The goal is to design a five-year nose-drop vaccine that would be effective for people of all ages. “It’s an entirely different concept from existing vaccines,” Arnon says. “The nose-drop vaccine - of which only a single drop will be needed - should effectively target a range of flu virus strains.”

Flu virus and hemagglutinin protein. Viral weak link

 

Not the common cold


The flu (or influenza) virus is different from the common cold. It attacks the respiratory tract (nose, throat and lungs) and usually comes on suddenly. Resulting symptoms include a fever, headache, congestion and muscle aches.


Most flu strains are mild, meaning that they have at least a few familiar features that our immune system recognizes and is able to fight - generally involving a recovery period of one to two weeks. Yet even with these mild flu strains, some people develop life-threatening complications, such as pneumonia - indeed, influenza annually claims the lives of roughly 36,000 people in the United States alone. Those at higher risk include toddlers, the elderly and people with chronic medical conditions, such as diabetes, asthma and heart disease.


Rarely, extremely virulent flu strains crop up that are so different in their genetic make-up our immune system is completely helpless - as in the pandemic of 1918, which killed between 20 and 40 million people around the world. One story tells of four ladies who were healthy enough to play bridge together into the night. Three of them were dead by the morning.


Prof. Arnon’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Milton A. and Charlotte R. Kramer Foundation; Mr. and Mrs. Eugene Applebaum, Bloomfield Hills, MI; Lester and Evelyn Burton, Bingham Farms, MI; Dr. and Mrs. Claude Oster, Bloomfield Hills, MI and Dr. and Mrs. Irving Slott, Chicago, IL. She is the incumbent of the Paul Ehrlich Professorial Chair of Immunology.

 

 
Prof. Ruth Arnon and Dr. Tamar Ben-Yedidia. Supervaccine
Life Sciences
English

The Effect of the Defect

English

Cohen, Visoly-Fisher and Cahen. outperforming single-crystal solar cells

Iris Visoly-Fisher knew exactly what she wanted to work on when starting her Ph.D. - to follow up on a hunch that defects in a certain material used in solar cells would actually improve their performance.


But something was bugging her. She couldn’t understand why so few people were working on this topic. “It was a no-man’s-land,” she says. “It seemed clear that something was up, but there was virtually no literature on it.”


She soon found out why. The technical difficulties in examining this puzzle were daunting. To effectively tackle the problem, she would need to figure out how to zoom in on solar cell performance on the nanoscopic scale (equal to roughly one hundred-thousandth the width of a human hair).


An unexplained finding from years earlier was what had triggered this headache of a challenge. Most commercial solar cells are made of single-crystal semiconductors, such as silicon, Visoly-Fisher explains. But researchers had been looking around for alternative materials for a while, given silicon’s high manufacture costs. Then, nearly 15 years ago, a finding came up that was out of sync with all theoretical predictions. Certain solar cells made of polycrystalline (multi-grained) films were systematically outperforming their counterpart single-crystal cells.


Nobody understood why. Scientists working to improve solar cells had traditionally shied away from multi-grained films, despite their being significantly cheaper, since they contained numerous structural defects - a property believed to impair the light conversion process.


“In examining and reexamining the multi-grained films that had proven so successful, we could come up with only one key difference between them and the single-crystal films: the presence of a leading defect, known as the grain boundary defect,” says Visoly-Fisher, who performed the study under the guidance of Prof. David Cahen of the Institute’s Materials and Interfaces Department, in collaboration with Dr. Sidney Cohen of the Institute’s Chemical Research Support.


The team decided to take a closer look at these defects by studying the electrical properties of a single defect - in other words, the meeting point between two of these microscopic grains. And this is where their technical problems began.


They started out using an imaging technique based on atomic force microscopy (AFM). But given the Lilliputian scale of their study, it was impossible to determine that the results obtained were in fact due to the grain boundary defect, rather than merely being an experimental artifact.


Only after combining three different high-resolution imaging techniques, did they have an irrefutable answer: “The results were clear, and quite astounding: Contrary to earlier notions, grain boundary defects significantly enhance the efficiency of certain solar cells,” says Visoly-Fisher.


The finding, which was recently published in Advanced Materials, has to do with the basic principle underlying most solar cells. When light strikes the cell, the semiconductor within it serves as an “antenna,” absorbing the light energy, which releases electrons present in the semiconductor, allowing them to flow freely. These electrons are then harvested as an electric current for external use. As the Institute team has now shown, grain boundaries within solar cell films improve the light-to-electricity conversion because they provide a path where the freed electrons are efficiently collected and channeled on their way out.


“The grain boundaries essentially function as a freeway for electrons to exit, without traffic lights or roundabouts,” explains Cahen. “This finding offers a promising direction for improving solar cell performance while cutting production costs.”


And Visoly-Fisher adds: “There’s something immensely satisfying about solving a long-standing question in materials science by examining how the building blocks of the device work at the nano-scopic level. It’s like gaining entry to an almost imaginary world.”


Part of this study was performed in the labs of Prof. Israel Bar-Joseph of the Institute’s Condensed Matter Physics Department and Dr. Arie Ruzin of Tel Aviv University’s Department of Physical Electronics.


Sun “raycing”


On a sunny day, the sun beams approximately 1,000 watts of energy per square meter on our planet. Success in tapping this resource would transform the world’s energy industry, meeting all of our power demands for free. Solar cells are also environmentally sound, lacking any corrosive chemicals and giving off no pollutants.


More work is needed before solar technologies can become cost effective, but they are playing an increasingly important role, more than tripling their market between 1995 and 2000. Around the world, engineering students, scientists and industrialists are pushing ahead with new solar technologies - from self-sustaining solar homes to solar-powered cars. For instance, in a project launched by the U.S. Department of Energy, contractors have just put the finishing touches to a pilot $800,000 luxury home in Livermore, California, that produces its own electricity and even sells its surplus power to the local utility company. This trend has widespread parallels in Germany, where, motivated in part by the Chernobyl nuclear disaster, the government is pitching in to introduce solar-power systems to residential, public and commercial buildings.


Solar-powered car races are already a huge hit. In 2003, for example, university students from around the world participated in the World Solar Challenge across the vast Australian outback, pitting their self-designed cars, powered only by the sun, in a rigorous 3,000-km race.


Prof. Cahen’s research is supported by the Philip M. Klutznick Fund for Research; the Delores and Eugene M. Zemsky Weizmann-Johns Hopkins Research Program; the Minerva Stiftung Gesellschaft fuer die Forschung m.b.H. and the Wolfson Advanced Research Center. He is the incumbent of the Rowland Schaefer Professorial Chair in Energy Research.

 
(l-r) Dr. Sidney Cohen, Dr. Iris Visoly-Fisher and Prof. David Cahen. Solar science
Chemistry
English

Discriminating Protein

English

Drs. Dan Tawfik and Amir Aharoni. Unknown origins

"Jack of all trades, master of an unknown,” is how Dr. Dan Tawfik of the Biological Chemistry Department describes a multi-purpose enzyme, nicknamed PON. The enzyme performs a variety of jobs in the body, including breaking down harmful chemicals found in pesticides and nerve gases and ridding the arteries of plaque-forming clumps of LDL (“bad cholesterol”) that can lead to arteriosclerosis. But these are just sidelines for PON, whose original function remains shrouded in its evolutionary past. Not only does it “moonlight,” accomplishing various jobs on the side, but it performs them inconsistently in different people, doing a sloppy job for some, a more efficient one for others. This is due to variations in its encoding gene. Referred to as polymorphism, this multiplicity of forms means, for instance, that some people’s PONs are up to 50 times more active than those of others.


How does one enzyme display such diverse performances? Very little was known about its workings when Tawfik and postdoctoral fellow Dr. Amir Aharoni decided to take a closer look.


To examine protein function, scientists apply crystallization, a process that yields X-ray images that are then translated into 3-D models. But crystallizing PON enzymes filtered from the blood - a process that yields only minuscule amounts - had proven difficult. So the team set out to create pure, genetically engineered proteins, generated in large enough quantities to crystallize and analyze them in detail.


The method they used, known as “directed evolution,” works on two principles of natural, Darwinian evolution: genetic diversity and survival of the fittest. Genetic diversity was created in the lab by inducing random mutations in the gene encoding the PON enzyme. The mutated enzymes were then inserted into bacterial cells, which were allowed to grow and multiply. Selection took place in the lab, with the scientists substituting for nature, deciding which were “fit” according to certain criteria, recombining them with other mutations and selecting again. Eventually, they found several versions of the enzyme that proved ideal for undergoing the procedures needed to solve its structure.


Studying the bacterial forms of the protein, the team succeeded in revealing many aspects of its function, including how its various forms in people differ in their ability to perform assigned tasks. They discovered, for instance, that the enzyme is shaped something like a six-bladed propeller and that modifications in its structure tend to take place near its active site (which performs the actual work of the enzyme) in a way that causes instability in the scaffold of the enzyme. They also got a good glimpse of how PON “roosts” on the HDL (“good cholesterol”) and the role it may play in sucking up oxidized lipids from the LDL (“bad cholesterol”) in arteries.


Once the main structure was solved, the research team tackled a new goal: that of creating new PON variants that would be even better at specific tasks than naturally occurring ones. Again using directed evolution, they came up with enzymes that could specialize in the chemical clean-up of harmful pesticides or reduce potential risk factors in heart disease. Interestingly, as the enzyme specialized in one task, it lost its ability to do others. “It’s similar to the jack-of-all-trades who takes up carpentry. Eventually he forgets how to do the plumbing and tile-laying,” says Tawfik.


Now that the team has a better picture of how differences in PON’s structure affect its actions in the test tube, they plan to focus on how it works inside the body. Research in this field might advance the treatment of arterio-sclerosis as well as of neuronal damage arising from exposure to harmful chemicals.


Other scientists collaborating in this research are Leonid Gaidukov of the Biological Chemistry Department; Prof. Israel Silman and Lilly Toker of the Neurobiology Department and Prof. Joel Sussman and Dr. Michal Harel of the Structural Biology Department.

One enzyme, several functions

 

Form fits function


To the uninitiated, diagrams of protein structures may look like colorful tangles of ribbon or free-style children’s art projects. Yet in proteins, as in architecture, form follows function.


Each protein consists of amino acids linked together in a long chain that folds and twists into the highly intricate shape in which it performs its specialized function.


When Sir John Kendrew and Max Perutz were awarded the Nobel Prize in 1962 for solving the first three-dimensional structures of proteins, they had spent over twenty years on the task. Even with today’s improved methods, much trial-and-error work is still involved, and scientists may spend months, even years, solving a protein’s structure.


The Israel Structural Pro-teomics Center (ISPC), based at the Weizmann Institute and headed by Prof. Joel Sussman of the Structural Biology Depart-ment, has made streamlining this process its main goal. Having tackled up to 30 proteins at a time in its pilot year, the Center intends to raise that number to several hundred in the coming years. Supported by the Ministry of Science, Culture and Sports, the ISPC facility is open to scientists throughout Israeli academia and industry interested in solving protein structures.


A major partner in a network of European structural proteomics centers (which Weizmann scientists were influential in establishing), the ISPC aspires to lead the way in protein research and open up new avenues in drug design and disease treatments.


Dr. Tawfik’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine; the Dolfi and Lola Ebner Center for Biomedical Research; the Estelle Funk Foundation; the Dr. Ernst Nathan Fund for Biomedical Research; the Henry S. and Anne Reich Family Foundation; the Harry and Jeanette Weinberg Fund for Molecular Genetics of Cancer and the Eugene and Delores Zemsky Charitable Foundation, Inc. He is the incumbent of the Elaine Blond Career Development Chair.

 

 
Drs. Dan Tawfik and Amir Aharoni. Pondering PON
Life Sciences
English

Going Magnetic

English

Prof. Ron Naaman. Magnetic and organic

When Itai Carmeli first came to his Ph.D. adviser with his results, he was gently told to get back to work. “I told him there was no such physics,” recalls a smiling Prof. Ron Naaman of the Institute’s Chemical Physics Department. “A year later he was back - with similar findings.”


Carmeli had been tinkering around with organic molecules, which he used to create extremely thin, single-layered films on a gold substrate. The surprise was that the films were behaving like a powerful magnet.


There are different types of magnets, Naaman explains, from the common fridge magnets we all played with as kids, which always display magnetic behavior; to temporary magnets such as paperclips and nails, which only work when exposed to a strong magnetic field; to magnets powered by an electric current. Nearly all of these contain one or more components with magnetic properties. The twist in our case was that the films lacked any magnetic materials.


In their study, recently published in Physical Review Letters and the Journal of Chemical Physics, the Institute team experimented with films made of three types of organic molecules. The molecules each had a positive and negative pole, and they were tightly packed, such that their negative poles faced the gold substrate, while their positive poles faced away. And this, says Naaman, might have been the trick: while opposite charges are known to attract, like charges repel, particularly when in close proximity on the surface of the film. The team - which included physicist Prof. Zeev Vager and materials scientists Prof. Shimon Reich and Dr. Gregory Leitus - believes that this repulsion force causes electrons to flow from the gold substrate to neutralize charged sites on the molecules in an attempt to stabilize the system. This extremely thin layer of flowing electrons in turn induces an electric current - forming a leading type of magnet dubbed an electromagnet (see box).


“We believe that the electrons are behaving as if in a co-op,” says Vager. “Electrons usually orbit in small circles, around individual molecules; but in this case they may be orbiting domains in the film containing hundreds of thousand of molecules, thus creating an electric current that transforms the system into a powerful magnet. Films of this sort might feature in electromagnets used in futuristic high-density discs and other electronics.”


Magnetic moments


Birds do it, bees do it, so do whales, salmon and, according to a new study, even Caribbean spiny lobsters - all use the Earth’s magnetic field as a navigating compass.

Magnetism was first discovered by the ancient Greeks and Chinese. Experimenting with the materials of their natural environment, they found that certain rare stones, called lodestones, attract small pieces of iron. Adding to their “magic,” these stones were found to always point in a north-south direction when suspended on a string. They quickly became invaluable to navigators, fortune-tellers and builders.


During the 13th century, French-man Pierre de Maricourt discovered that magnets had two magnetic poles - north and south - and in the 1600s, England’s Sir William Gilbert concluded that Earth itself was a giant magnet with north and south poles - which explains the wonder of animal migration treks.


The 1800s saw the first connection made between electricity and magnetism, when Danish physicist Hans Christian discovered that running an electric current through a wire creates a magnetic field - a phenomenon that quickly became known as electromagnetism. And today, this form of magnetism is everywhere - in the electric motors in refrigerators, washing machines and racecars; the read/write heads of discs and videotape players, and far more.


Prof. Naaman’s research is supported by the Fritz Haber Center for Physical Chemistry; the Ilse Katz Institute for Material Sciences and Magnetic Resonance Research; the Wolfson Advanced Research Center; the Philip M. Klutznick Fund for Research, Chicago, IL; and Dr. Pamela Scholl, Northbrook, IL. He is the incumbent of the Aryeh and Mintze Katzman Professorial Chair.

 
Prof. Ron Naaman. Electrons in a co-op
Space & Physics
English

Tap Water Truths

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Prof. Brian Berkowitz. chemical cocktail

When you open a water tap, chances are good that the water is being pumped from underground reserves called aquifers. Like a giant sponge, spaces in the porous rock or sand beneath the surface hold water that soaks in from above ground. Many aquifers, especially those near heavily populated coastlines, are threatened by overpumping, which causes the nearby seawater to be sucked in as fresh water is removed. Weizmann scientists have now revealed that this meeting of salt and fresh waters might negatively affect underground water quality even before it becomes too salty to drink.


The study was performed by Prof. Brian Berkowitz, postdoctoral fellow Dr. Ishai Dror and Tal Amitay, all of the Institute’s Environmental Sciences and Energy Research Department, and Dr. Bruno Yaron of the Agricultural Research Organization - Volcani Center.


The team found that certain chemicals typical of those in industrial and agricultural waste are capable of mixing into seawater.


“Most scientists had assumed that these pollutants would behave either like oil slicks, floating on the seawater, or like sludge, sinking to the bottom,” says Berkowitz. “But we found that a mixing process similar to wave action shakes up the water and chemicals like oil and vinegar in a bottle, forming micro-emulsions - tiny drops of one liquid suspended in another. The implication was that relatively large amounts of these chemicals could be distributed throughout seawater, which theoretically could then be carried into the groundwater.”


But the story does not end there. In the experiments, chemicals added to the salt water refused to stick around with the salt, rushing into the freshwater like salmon in mating season.


In these experiments, glass tanks were divided in half, horizontally, by a sand barrier. In some tanks, freshwater containing a cocktail of five chemicals was placed on one side and clean freshwater on the other, while in other tanks the chemical mix was added to saltwater, with clean freshwater placed on the other side. When the water on the “clean” side of the barriers was analyzed after a period of time, the scientists found that the contamination levels in water that bordered on saltwater were many times higher that those from the all-freshwater tanks. One particular chemical compound did not cross the barrier at all in the freshwater trials, but did so in the salty ones. Though some straying to the other side was to be expected, clearly another process was at work.


A phenomenon known as salting out is to blame. The salt ions fill in the spaces between the water molecules, shutting out all other molecules and thereby driving the droplets of pollutants into the fresh- water, where they can co-exist more easily.


“Aside from being a cool demonstration of a scientific principle, the experiment reveals only what happens in a glass tank in the lab, not in the far more complex underground systems,” Berkowitz emphasizes. He estimates that at least a year of additional lab work is required, testing different combinations of barriers, water flows, chemicals and minerals, before they can begin to check whether real-life aquifers might be under threat or how they could be protected.


Prof. Berkowitz’s research is supported by the Sussman Family Center for the Study of Environmental Sciences; the Angel Faivovich Foundation for Ecological Studies; the Brita Fund for Scholarships Research and Education, the Feldman Foundation; the P. and A. Guggenheim-Ascarelli Foundation; Mr. and Mrs. Michael Levine, Pinckney, NJ; and the late Mrs. Jeannette Salomons, the Netherlands. He is the incumbent of the Sam Zuckerberg Professorial Chair in Hydrology.

 
Prof. Brian Berkowitz. A matter of salt
Environment
English

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