Unlikely Pairs

English

An electron interferometer: Pairing of electrons takes place in the path denoted by the broken red line

 

 

 

 

 

 

 

 

 

 

“Can two walk together, except they be agreed?” (Amos 3:3)

 

The prophet Amos believed in a rational, ordered world, in which everything can be explained by cause and effect. That ideal fits the world of science – once in a while. Sometimes when the cause is known, the ensuing effects can be predicted. But more often scientists try to measure something that “should be there,” or else they discover new phenomena that have no apparent reason or cause. Indeed, most scientific research arises from these two starting points, working from opposite directions to connect cause with effect.

 
Prof. Moty Heiblum
 
Prof. Moty Heiblum of the Condensed Matter Physics Department and his research group recently conducted an experiment looking for an effect that “should be there” and ended up with an unexplained phenomenon. Working in the Braun Center for Submicron Research, the group was experimenting with a phenomenon known as the quantum Hall effect. In this system, electrons flow in a two-dimensional plane and are exposed to a strong magnetic field perpendicular to the plane. The electrons, which “prefer” to run in straight lines, get pulled from their original paths by the magnetic field and end up traveling around the edges of the plane.

But what Heiblum and his group observed in the electron flow seemed to belong to a different type of system: superconductivity. Electrons, which all carry negative charges, normally repel one another. However, under very special conditions, in some materials and at extremely low temperatures, electrons can actually “hook up” to form pairs called Cooper pairs. Cooper pairs can move through a material with no resistance whatsoever, and this state is thus known as superconductivity.

So it came as a great surprise to discover electrons pairing up under certain conditions in their quantum Hall system – forming pairs that were remarkably similar to Cooper pairs. This is, indeed, the first time that this phenomenon has been observed outside of superconductivity, and the scientists are still not quite sure what to make of it.

Once the electrons are pulled from their path by the magnetic field and forced to flow near the edges of the quantum Hall system, they travel in “parallel lanes” at varying distances from the edge. The scientists are now wondering if the close proximity of electrons moving in those parallel lanes could somehow cause electrons to “feel” one another more strongly and, consequently, interact in a different manner than the ubiquitous repulsion.

The phenomenon was observed at the exit to the system. Electrons leaving the outer lane were measured; the surprise came when the exiting charges were found to be twice that of a normal, single electron. In other words, the current was carried by paired electrons, similar to that of Cooper pairs that flow so freely in the superconducting state.

Although this phenomenon was completely unexpected and is still not understood, the question asked by the prophet Amos, with his insistence on rational cause and effect, resonates with the scientists: Why do these pairs of electrons “walk together,” apparently in total “agreement”? What causes the electrons in this system to form pairs? Or conversely, what is the effect of electron pairing on the functioning of the system? The Weizmann Institute scientists are already conducting new experiments to help sort out the riddle of the quantum Hall electron pairs.  
 
Prof. Moty Heiblum’s research is supported by the Joseph H. and Belle R. Braun Center for Submicron Research, which he heads; the Gruber Center for Quantum Electronics, which he heads; the Willner Family Leadership Institute for the Weizmann Institute of Science; the Dan and Herman Mayer fund for Submicron Research; the Wolfson Family Charitable Trust; the European Research Council; and the estate of Olga Klein Astrachan. Prof. Heiblum is the incumbent of the Alex and Ida Sussman Professorial Chair of Submicron Electronics.
 
 
An electron interferometer: Pairing of electrons takes place in the path denoted by the broken red line
Space & Physics
English

Quantum Attraction

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(l-r) Prof. Gershon Kurizki and Ephraim Shahmoon

Even a perfect vacuum is not truly empty. If you could observe that vacuum on the quantum, atomic or subatomic scale, you would see a “bubbling soup” of  "ghost" particles. Known as “virtual particles,” they randomly pop in and out of existence in the empty space; and they cause a phenomenon known as vacuum fluctuation. So, in a space that is completely devoid of any detectable radiation – that is, a vacuum existing at the temperature of absolute- zero – fluctuations in electromagnetic fields will still be taking place on a microscopic, quantum scale.

 
 
 
Though they are called virtual, these particles create real forces between atoms. If you place two atoms close together, they will change the local vacuum between them, creating fluctuations through virtual photons – light particles. The attraction between these close-together atoms is called the van der Waals force. Place the atoms farther apart, and you will still observe a slight pull between them. This is the Casimir force. Both of these forces are weak and often hard to measure.

Prof. Gershon Kurizki and research student Ephraim Shahmoon, of the Weizmann Institute’s Chemical Physics Department, together with Dr. Igor Mazets of the Vienna University of Technology recently suggested a way of enormously enhancing these forces – until they become a sort of “quantum glue” holding atoms together. In their paper, recently published in the Proceedings of the National Academy of Sciences (PNAS), the researchers considered atoms placed near a line of conducting material, similar to an ordinary coaxial cable used to hook a TV to a satellite dish. In the setup they envision, a  virtual photon that is emitted from one atom would be confined so that it propagates in one dimension to the nearest atom down the line, where it would be absorbed, then reemitted back to the first atom and so on.
Possible "quantum glue" setup: Coaxial line: two concentric metallic cylinders, the inner one with radius a and the outer (hollow) one with radius b. Two dipoles represented by black circles are placed in between the cylinders, along the wave propagation direction z. They interact via modes of the coaxial line that are in the vacuum state, giving rise to a vdW-like interaction energy
 

Having this exchange of virtual photons occur under one-dimensional confinement, rather than in everyday three-dimensional space, greatly increases the odds that the process will take place. The researchers’ calculations suggest that the attraction between atoms via virtual photons in the electric coaxial cable could be millions of times greater than that in three-dimensional space, transforming a  normally weak force into potent " glue." This research was highlighted in the journals Physics Today and Nature Photonics.

If scientists manage to demonstrate such one-dimensional vacuum forces, their experiments could help us understand the phenomena surrounding virtual particles.

 
Prof. Gershon Kurizki’s research is supported by the Mary and Tom Beck-Canadian Center for Alternative Energy Research. Prof. Kurizki is the incumbent of the George W. Dunne Professorial Chair of Chemical Physics.
 

 

 
 

 
 
(l-r) Prof. Gershon Kurizki and Ephraim Shahmoon
Space & Physics
English

Rewiring

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Our brain’s networks are shaped, among other things, by our bodily interactions with the environment. How do our physical, daily activities affect our brain networks? Research student Avital Hahamy and Prof. Rafi Malach of the Neurobiology Department teamed up with a group of researchers at Oxford University, led by Dr. Tamar Makin, to find an original way to explore this question. Using functional magnetic resonance imaging (fMRI), they compared the resting brain activity of individuals who had been born lacking a hand with a control, “two-handed,” group.
 
Avital Hahamy and Prof. Rafi Malach
        

 

 
 
Malach’s group has helped develop the field of resting brain research: When brains are at rest, spontaneous patterns of brain activity emerge across their two hemispheres, revealing how corresponding areas synchronize their activity. In this study, which recently appeared in eLife, the researchers were looking at the level of synchronization between the brain areas in each hemisphere that control the movements of the two hands. They asked whether the absence of a hand can change the levels of synchronization between the corresponding brain regions. The researchers also wanted to understand if changes in brain synchronization may relate to daily behaviors, especially the ways in which one-handed individuals physically compensate for their physical disability. In other words, how does brain activity during the resting state reflect routine, every-day behavior?
 
The researchers found that individuals lacking a hand had less synchronization between the brain regions controlling hand movements than that of two-handed people. However, these differences appeared to depend on each person's habitual behavior: The less a person used his stump as a hand, the less synchronization was apparent in his brain. In contrast, individuals who compensated for the absence of a hand by using their stump as a hand showed high synchronization of brain activity, resembling that of two-handed people. In other words, say the researchers, the deep-seated coordination between the two halves of our brain and the physical coordination between the two sides of our bodies go hand in hand (so to speak). The findings hint, more broadly, at how our daily behaviors are "encoded" in our resting brain activity.
 
Prof. Rafael Malach's research is supported by the Murray H. and Meyer Grodetsky Center for Research of Higher Brain Functions, which he heads; and Friends of Dr. Lou Siminovitch. Prof. Malach is the recipient of the Helen and Martin Kimmel Award for Innovative Investigation; and he is the incumbent of the Barbara and Morris L. Levinson Professorial Chair in Brain Research.




 
 

 
 

Avital Hahamy and Prof. Rafi Malach
Life Sciences
English

Stopping the Stem Cell State

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Stem cell colony with cells in the process of differentiation; from the lab of Dr. Jacob Hanna
 
Scientists can now create cells that closely resemble embryonic stem cells in the lab. But what happens next? Because the use of these cells, called induced pluripotent stem (iPS) cells, to treat disease will ultimately depend on how we learn to direct their fate, we also need to figure out how they stop being stem cells – a process that naturally takes place right at the beginning of embryonic development. “The system must be shut off before differentiation into the various cell types can proceed,” says Dr. Jacob Hanna of the Weizmann Institute’s Molecular Genetics Department. “We have gotten somewhat proficient at getting the cells to revert, but very little is known about the termination of the iPS program.”

To investigate, Hanna and research student Shay Geula teamed up with Prof. Gideon Rechavi of Chaim Sheba Medical Center in Tel Aviv, and their findings recently appeared in Science. Hanna’s group is making strides in the field of iPS cell research; Rechavi’s group is one of the world’s leading experts in another little-known area, called RNA methylation.

Methylation is a basic biochemical process: A chemical “methyl” group gets attached to a genetic sequence, blocking it off from further use. In the better-known version, DNA methylation, the process is often described as a lock – hard to open again and relatively long-lasting. Some types of methylation can even be passed down to the next generation. So when Rechavi’s group and others noted that the short-lived genetic sequences of RNA can also be marked by methyl groups, it was unclear to what purpose.

The researchers identified an enzyme – Mettl3 – that attaches methyl groups to the RNA of mammalian cells. To see whether this action plays a role in undoing the stem-cell state, they silenced the gene for this enzyme in mouse embryos. The consequences were devastating: The embryos were not viable for more than a few days. Development didn’t progress as cell differentiation could not proceed properly.

A closer look at the actions of Mettl3 revealed that it attaches its methyl groups to the exact sequences that code for pluripotency – the capacity to become any cell type. Rather than simply locking these sequences, the methylation causes them to be broken down.

Hanna: “These findings showed that, on the one hand, RNA methylation plays a crucial role in embryonic development and, on the other, that it is not enough to reinstate the stem cell program. It must be turned off again, at the right time and in the right way, for the next step in cell differentiation to take place. RNA methylation is the dominant mechanism that safeguards adequate dismantling and decay of the stem cell state.”  
 
Dr. Jacob (Yaqub) Hanna
                               
 

Dr. Jacob Hanna's research is supported by Pascal and Ilana Mantoux, France/Israel; the Benoziyo Endowment Fund for the Advancement of Science; the Leona M. and Harry B. Helmsley Charitable Trust; the Sir Charles Clore Research Prize; Erica A. Drake and Robert Drake; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the European Research Council; the Fritz Thyssen Stiftung; and the Alice and Jacob K. Rubin Charitable Remainder Unitrust. Dr. Hanna is the recipient of the Helen and Martin Kimmel Award for Innovative Investigation.
 

 
 
Stem cell colony with cells in the process of differentiation; from the lab of Dr. Jacob Hanna
Life Sciences
English

Artificial Cells Produce Real Proteins

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A living cell, from one point of view, is a sort of sprawling protein factory that can churn out thousands of different proteins to order. Prof. Roy Bar-Ziv of the Weizmann Institute’s Materials and Interfaces Department is building on the basic idea of creating “artificial cells” that might, in the future, enable us to control the production of proteins or other complex biological processes.

 
Fluorescent image of DNA (white squares) patterned in circular compartments connected by capillary tubes to the cell-free extract flowing in the channel at bottom. Compartments are 100 micrometers in diameter
 

 

 

The system, designed by PhD students Eyal Karzbrun and Alexandra Tayar in Bar-Ziv’s lab, in collaboration with Prof. Vincent Noireaux of the University of Minnesota, comprises multiple compartments etched onto a biochip. These tiny artificial cells, each a mere millionth of a meter in depth, are connected via thin capillary tubes, creating a network that allows the diffusion of biological substances throughout the system. The instructions – DNA designed by the scientists – are inserted into the cells, along with the protein-making machinery and raw materials – both provided by an extract of the bacterium E. coli.


The genetic sequence the researchers had inserted contained two regulatory genes – basically “on” and “off” switches. Much like their real counterparts, the artificial cells are linked through a capillary system to a feeding channel that enabled them to absorb nutrients and exchange materials; and they, in turn, created proteins in a periodic fashion.

(l-r) Eyal Karzbrun, Alexandra Tayar and Prof. Roy Bar-Ziv
The network also mimicked a key facet of complex cellular communication – one that takes place during embryonic development. As the body plan takes shape – a process called morphogenesis – the diffusion of proteins out of the cells becomes crucial. Tayar: “We observed that when we place a gene in a compartment at the edge of the array, it creates a diminishing protein concentration gradient; other compartments within the array can sense and respond to this gradient – resembling an embryo during early development. We are now working to expand the system and to introduce gene networks that will mimic pattern formation, such as the striped patterns that appear during fly embryogenesis.”
 
Bar-Ziv: “Genes are like Lego in which you can mix and match various components to produce different outcomes; you can take a regulatory element from E. coli that naturally controls gene X, and produce a known protein; or you can take the same regulatory element but connect it to gene Y to get different functions that do not naturally occur in nature.” This research may, in the future, help advance the synthesis of such things as fuel, pharmaceuticals, chemicals and the production of enzymes for industrial use, to name a few of the possibilities.
 
Prof. Roy Bar Ziv's research is supported by the Yeda-Sela Center for Basic Research.
 
 

 

 

 

 
(l-r) Eyal Karzbrun, Alexandra Tayar and Prof. Roy Bar-Ziv
Chemistry
English

Weakness into Strength

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Magnetic resonance image of a rat’s brain subjected to a partial stroke in the right hemisphere (black square); the left hemisphere remained intact (green square)
 
 
The living brain teems with small molecules: These are metabolites that, among other things, transmit neuronal messages, supply energy and synthesize membranes. But when it comes to monitoring the workings of the living brain, the prime noninvasive methods available for this purpose – magnetic resonance imaging (MRI) and related magnetic resonance technologies – provide information only about the water in which these vital molecules are dissolved, not about the metabolites themselves. As reported recently in Nature Communications, Weizmann Institute researchers, in collaboration with scientists from the National High Magnetic Field Laboratory in Florida, have now devised a sophisticated magnetic resonance technique for directly monitoring metabolites.
 
MRI technologies enable the imaging of living tissue by placing it inside a static magnetic field and exciting the tissue’s atoms with a weak electromagnetic wave in the radiofrequency range. This excitation causes the atoms to oscillate, and magnetic resonance equipment measures the oscillation frequencies for the various atoms.  MRI is normally employed to monitor hydrogen, ubiquitous in all living tissue and a main component of water. But the availability of metabolites is about 10,000 times lower than that of water – their magnetic resonance signals are drowned out by the water when standard MRI is applied.
 
In a new study performed on rats, researchers successfully applied advanced magnetic resonance methods to measure several brain metabolites whose levels are known to be altered by stroke. The findings, obtained immediately after the rats underwent a stroke as well as during their recovery, matched patterns known from such invasive studies as the sampling of brain fluids. Furthermore, the research revealed the microarchitecture of brain structures housing the metabolites in healthy brains and in the areas affected by stroke. These microscopic structures were significantly distorted after the stroke, evidently due to swelling and lack of oxygen.
 
Graphs of magnetic resonance spectra illustrate how the levels of metabolites in the brain’s hemisphere affected by stroke (black) were altered compared with those in the healthy hemisphere (green)
 

 

A key factor that made the study possible was the use of an extremely strong magnet of 21 tesla, presently available only for research on rodents; this far exceeds the sensitivity of current clinical MRI systems, which operate at 3 tesla. Another crucial factor was the magnetic resonance approach itself: The scientists performed the scanning using a new sequence of radiofrequency pulses that excited the metabolites’ hydrogen atoms but left the water’s hydrogen practically undisturbed. Thus they were able to observe the weak signals emitted by the metabolites while avoiding the much stronger signal emitted by the water. In addition, the method allowed the scientists to exploit the fact that with this selective excitation, metabolites revert from the excited state to equilibrium much faster than does water’s hydrogen, which also facilitated signal collection. The study was performed by Prof. Lucio Frydman and Drs. Noam Shemesh and Jean-Nicolas Dumez of the Weizmann Institute’s Chemical Physics Department, and Prof. Samuel Grant, Dr. Jens Rosenberg and Jose Muniz of the National High Magnetic Field Laboratory in Tallahassee, where the 21 tesla system is housed.

This research opens up new possibilities for studying the living brain by monitoring its metabolites. Such monitoring may in the future be developed into a safe, noninvasive method for diagnosing stroke, as well as for detecting early signs of various brain disorders in which metabolite levels are altered, among them Parkinson’s disease, schizophrenia and Alzheimer’s disease.
 
Prof. Lucio Frydman's research is supported by the Helen and Martin Kimmel Institute for Magnetic Resonance Research, which he heads; the Helen and Martin Kimmel Award for Innovative Investigation; the Ilse Katz Institute for Material Sciences and Magnetic Resonance Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; the Mary Ralph Designated Philanthropic Fund of the Jewish Community Endowment Fund; Gary and Katy Leff, Calabasas, CA; Paul and Tina Gardner, Austin, TX; and the European Research Council.
 
 
Magnetic resonance image of a rat’s brain subjected to a partial stroke in the right hemisphere (black square); the left hemisphere remained intact (green square)
Chemistry
English

How Cells Feel the Stretch

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Top right: Before force is applied, cells grown in culture are randomly oriented. Top left: As a result of cyclic stretching, the cells organize in a uniform orientation. Bottom left: Following the cyclic stretching, cell skeletal fibers (“compressed springs,” red) align at the same angle as the cell body. Bottom right: Focal adhesions (green) at the ends of cellular skeleton fibers (red)

 
As our blood vessels pulsate with each heartbeat or our lungs inflate, the cells in these vessels and organs stretch as well. Such cells, which sense rhythmic fluctuations in force, have been found to neatly align at a very uniform angle. But how do they know in which direction to orient themselves? A new look at this process suggests that dozens of tiny individual adhesion sites at the cell’s outer edges collectively “steer” the entire cell so that it points in the right direction. These findings were recently published in Nature Communications.  
   
Observations in the last decade or two have revealed that cells can sense and respond to mechanical perturbations. When cells are repeatedly stretched together with an underlying substrate to which they adhere, they tend to align – more or less – in the direction they are stretched the least. For Dr. Ariel Livne in the lab of Prof. Benjamin Geiger in the Molecular Cell Biology Department, it was this “more or less” that was problematic. The researchers realized that something was missing from the models used to predict how a cell will behave when exposed to cyclic forces.
 
Cells that are being stretched may still hold on to the underlying surface through focal adhesions – “sticky” contact points around their edges. Running between the focal adhesions is a network of cellular skeleton fibers that effectively behave as “compressed springs.” Existing models for cell reorientation under cyclic stretching focused primarily on these springs, assuming they were the driving element behind a cell’s change of direction.
(l-r) Dr. Ariel Livne, Prof. Benjamin Geiger and Dr. Eran Bouchbiner
 
But Livne’s precise experiments and analysis showed that stretching the individual springs could not account for the observed cell orientations. In collaboration with Dr. Eran Bouchbinder of the Chemical Physics Department, a theoretician who studies the physics of complex systems, including the physical behavior of surfaces that experience forces, the team developed a theory to describe the responses of focal adhesions to alternating forces. This theory was highly successful at predicting not only the new direction in which cells realign, but also the rate of the entire rotation process. Thus the reorientation of the entire cell appears to begin at the “grass roots” through individual changes in the contact points at the cell edges. 
 
Prof. Benjamin Geiger’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; the Fondazione Henry Krenter; Paul and Tina Gardner, Austin, TX; David and Molly Bloom, Canada; the estate of Anne S. Lubliner; the estate of Raymond Lapon; the estate of Alice Schwarz-Gardos; and the European Research Council. Prof Geiger is the incumbent of the Professor Erwin Neter Professorial Chair of Cell and Tumor Biology.
 
(l-r) Dr. Ariel Livne, Prof. Benjamin Geiger and Dr. Eran Bouchbiner
Life Sciences
English

Stark Contrast

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Prof. Michael Elbaum and Dr. Sharon Grayer Wolf
 
“At first sight, it's a mix of methods that couldn't possibly work together, and yet we have found it to work very well,” says Prof. Michael Elbaum of the Weizmann Institute’s Materials and Interfaces Department. Together with Dr. Sharon Grayer Wolf of Weizmann and their colleague Dr. Lothar Houben from the Ernst Ruska Center in Juelich, Germany, the team has developed a new approach to imaging biological samples in three dimensions using an electron microscope.
 
An electron microscope is a powerful tool able to image specimens at extraordinarily high magnification and resolution, allowing scientists to see cells, molecules and sometimes even atoms. But the microscope’s harsh environment – high vacuum and merciless bombardment with electrons – is hard on biological specimens, damaging and distorting their delicate structures. Added to this, the sample must scatter electrons – without absorbing their energy – in order to form a high-contrast image. Because biological samples are not very good at scattering electrons, a classic approach is to stain organic structures with atoms of heavy metals. This enhances contrast in the images, but the preparations can cause additional harm to the already-delicate specimen. A newer method involves the ultra-rapid cooling of biological specimens. The cooling is so fast that the surrounding water instantly solidifies into “glass” without crystallizing and so preserves proteins and cells in true-to-life form. This protects them against the vacuum, but the problem of weak scattering remains an issue. In addition, in 3D tomography, the samples need to be imaged from many angles, which can exacerbate the problem.
 
 
Conventional imaging methods that illuminate the entire sample area all at once are plagued by haze because of random scattering. If the sample is thick, a special filter is required, which can throw away 90% or more of the already-weak imaging signal. The team found that by configuring the transmission electron microscope (TEM) to scan the sample point by point – a method that is standard in materials science but not in biology – the haziness could be neutralized without losing signal. “It's a bit like searching at night,” says Elbaum.  “Due to the way that electrons interact with matter, unstained biological specimens are always ‘foggy.' When it's clear, a floodlamp is fine, but in a fog it's better to search with a focused flashlight.” The TEM detectors were also adjusted so as to collect their signals at unusually low angles. This aspect of the new method – recording the weakly scattered electrons at sufficiently low angles – is not at all standard.
 
The scientists were able to “hack” the available hardware to meet their needs, and the results were striking: The unconventional configuration revealed images with superb contrast. Such an outcome had previously been considered so unlikely that this experimental setup had not until now been attempted. The scanning beam method allows the use of samples two to three times thicker than had previously been possible.
Sub-cellular structures of the common soil bacterium Agrobacterium tumefaciens are visible in greater detail using the new STEM technique (left) than by traditional TEM-based cryo-tomography (right) Scalebars = 200 nm
 
Indeed, to test this newly adapted method, the team imaged such “gigantic” (for a conventional TEM) specimens as whole bacterial cells, as well as human tissue culture cells. The improvements surprised even the scientists: High-contrast, good quality three-dimensional images were being produced that were much better and clearer than those obtained by the traditional TEM method.
 
This new technique, recently published in Nature Methods, should broaden the applicability and accessibility of transmission electron microscopes for biological research. Wolf: “To extract the best results from three-dimensional TEM imaging of ultra-rapidly cooled specimens, very expensive equipment is required. In comparison, the hardware for STEM capability is a simple add-on to an existing modern TEM, which offers a path into the field for many researchers.” The scientists plan to improve upon this method even further, including designing new tools to optimize the data collection.
 
Elbaum: “The multidisciplinary nature of the Weizmann Institute has frequently been instrumental in the pursuit of unconventional ideas and technology, and the Electron Microscopy Unit, supported by the Moskowitz Center for Nano and Bio Nano Imaging, is really a case in point. Few places in the world would enable such close encounters of scientists with different areas of expertise, let alone give them the freedom to focus together on a risky project. At Weizmann it was entirely natural.”

 

Prof.  Michael Elbaum’s research is supported by the Irving and Cherna Moskowitz Center for Nano and Bio Nano Imaging, which he heads; the Louis and Fannie Tolz Collaborative Research Project; and Sharon Zuckerman, Canada.
 

 
Prof. Michael Elbaum and Dr. Sharon Grayer Wolf
Chemistry
English

Risk Assessment

English

 

Standing: (l-r) Drs. Yael Leitner-Dagan and Ziv Sevilya, and Dalia Elinger. Sitting: Prof. Zvi Livneh and Dr. Tamar Paz-Elizur
 

 

Some 85% of smokers never get lung cancer, while a small percentage of unlucky non-smokers fall prey to the disease. Smoking is, of course, still the main known risk factor, but a test for susceptibility to this cancer could help prevent many deaths. Recent Weizmann Institute research suggests that a combined test for three different biological markers provides a “DNA repair score” revealing an individual’s odds of developing lung cancer.  

Prof. Zvi Livneh and Dr. Tamar Paz-Elizur of the Biological Chemistry Department have been investigating such markers – biological molecules that are over- or under-active – for the past several years. Their research has focused on the DNA repair mechanisms in the cells for mending the damage caused, among other things, by the harmful substances in tobacco smoke. The assumption is that even small deficiencies in these repair mechanisms could allow cancer processes to begin. Indeed, the team found one such molecule, an enzyme called OGG1, whose activity is strongly associated with lung cancer: Very low levels of OGG1 activity increased the risk of this cancer fivefold.
 
 
Although checking for OGG1, alone, could give a good indication of cancer risk, Livneh and his team continued searching for further DNA repair mechanisms in hopes of improving the test and narrowing the margin of error. Around a year ago, they discovered a second factor, called MPG, which is linked to the tendency to develop lung cancer. Surprisingly, it was high levels of MPG activity, rather than low ones, which were associated with increased risk. The researchers think that a balance between OGG1, MPG and other DNA repair enzymes is critical; imbalances between them may lead to inefficient repair efforts.
DNA repair mechanism. Image: Wikimedia Commons
 
Now, in a study that was recently published in Cancer Prevention Research, Livneh, Paz-Elizur and Drs. Ziv Sevilya and Yael Leitner-Dagan, and Dalia Elinger; in collaboration with Prof. Gad Rennert, Dr. Mila Pinchev and Hedy Rennert of the Technion School of Medicine and Carmel Medical Center; Dr. Ran Kremer of Rambam Medical Center; Prof. Laurence Freedman of Sheba Medical Center; and Prof. Edna Schechtman of Ben-Gurion University of the Negev, have found that a third DNA repair enzyme, called APE1, is also strongly tied to lung cancer risk. Higher risk came with reduced APE1 activity, although, interestingly enough, it has been known to be overexpressed in certain established cancers. The scientists think that APE1 may play a dual role in cancer: In healthy cells it acts weakly, allowing the accumulation of mutations that can speed up the development of cancer; while in cells that have already become cancerous, increased APE1 activity grants an advantage, enabling faster DNA replication and proliferation.

The researchers developed a method of weighting the levels of all three biomolecules in the form of a “DNA repair score,” along with the history of smoking, to determine the total risk. Checking these factors in 100 lung cancer patients and comparing them with those of healthy people, they found that people with a low DNA repair score have a 10-20-fold increase in their risk of getting lung cancer. While larger-scale clinical trials are needed to confirm the efficacy of the so-called OMA (OGG1-MPG-APE1) DNA repair score – a personalized measure of DNA repair activity – Livneh is optimistic that it will become a powerful tool for assessing cancer risk and directing individuals at risk to seek early detection though proactive CT scans. In addition, a study is planned to search for novel drugs that will improve DNA repair as a strategy to reduce the risk of lung cancer and perhaps other types of cancer.
 
Prof. Zvi Livneh’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine, which he heads; the Leona M. and Harry B. Helmsley Charitable Trust; the David M. Polen Charitable Trust; Dana and Yossie Hollander, Israel; Mike and Valeria Rosenbloom through the Mike Rosenbloom Foundation; and the Sergio Lombroso Award for Cancer Research. Prof. Livneh is the incumbent of the Maxwell Ellis Professorial Chair of Biomedical Research.
 
Prof. Zvi Livneh’s research is supported by the Y. Leon Benoziyo Institute for Molecular Medicine, which he heads; the Leona M. and Harry B. Helmsley Charitable Trust; the David M. Polen Charitable Trust; Dana and Yossie Hollander, Israel ; Mike and Valeria Rosenbloom through the Mike Rosenbloom Foundation; and the Sergio Lombroso Award for Cancer Research. Prof. Livneh is the incumbent of the Maxwell Ellis Professorial Chair of Biomedical Research.
DNA repair mechanism. Image: Wikimedia Commons
Life Sciences
English

Seeing the Unseen

English

 

Invisible Coral Flows, the winning photography entry

 
Corals are far from the “living rocks” they are sometimes taken to be. Invisible Coral Flows, which won first place in the photography category of the 2013 Science/National Science Foundation International Science & Engineering Visualization Challenge, captures the unseen flow generated by small hairs – cilia – covering the surface of a reef-building coral. The lines of flow reveal a previously unknown way in which the coral actively draws in nutrients and sweeps away waste products from the colony surface. The image was featured on the cover of Science, February 7, 2014.

It was created through an ongoing collaboration between Dr. Assaf Vardi of the Weizmann Institute of Science’s Plant Sciences Department and Prof. Roman Stocker of the Massachusetts Institute of Technology (MIT). This research was funded by a grant from the Human Frontiers Science Program (HFSP).

To highlight the flow, Dr. Orr Shapiro of Vardi’s group – at the time a guest of Stocker’s group – and Dr. Vicente Fernandez of the Stocker lab used video microscopy to track particles in the water next to the coral surface. After recording two short videos 90 minutes apart and superimposing the successive frames from each video, they overlaid the resulting images to create the final composition. Artist considerations had a role as well: Drawing inspiration from Andy Warhol’s striking palette, the scientists used false color to help visualize the system. Pink represents the position of two coral polyps (Pocillopora damicornis) that were roughly 3 millimeters apart at the start of the video; purple represents their changed position at a later time; and gold and cyan highlight the flow patterns at the two time points, respectively. The spacing between points in the tracks represents different particle speeds, revealing where the flow is strongest in the vortex.

The image of the particle trajectories – not only rich in visual texture and form, but also in the amount of information they convey – made this photo a unanimous winner according to the judges.

“The image captures the beauty of coral-generated flows and epitomizes our discovery of their dramatic role in mass transport. Our finding has changed the way we think of corals – from passive entities dependent upon external flows, to active engineers of their own microenvironment,” says Shapiro. This new discovery has direct impacts on our understanding of corals’ physiology and their potential ability to cope with changes in their environment.
 
Dr. Assaf Vardi's research is supported by Charles Rothschild, Brazil; Roberto and Renata Ruhman, Brazil; Luis Stuhlberger, Brazil; the Lord Sieff of Brimpton Memorial Fund; the European Research Council; and the estate of Samuel and Alwyn J. Weber. Dr. Vardi is the incumbent of the Edith and Nathan Goldenberg Career Development Chair.


 
 
Invisible Coral Flows, the winning photography entry
Environment
English

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