Think Positive

English
Prof. Eli Waxman
 
Over the past few years, the astronomers monitoring the data from the PAMELA satellite mission have reported a surprising phenomenon: They identified a strong stream of positrons not far from Earth. Positrons are “anti-electrons” – particles that are identical to electrons in all ways save their charge, which is positive as compared to the electrons’ negative one. Where do these positrons come from? How are they created?
 
The existence of the positrons was not a surprise: The mission, which explores cosmic rays, was looking for positrons. Astrophysicists believe that the source of these positrons is cosmic ray collisions that occur in the interstellar gas. Such collisions create short-lived particles that, as they perish, produce various other particles, including positrons. The surprise was in their number, which was much higher than models had predicted. So the question was: Where do the excess positrons come from?

A number of theories have arisen; many of them are based on “dark matter” – the invisible stuff that, if it exists, would explain several anomalies in the astronomical observations of gravity.

Prof. Eli Waxman, and former research students Kfir Blum and Boaz Katz, wondered if dark matter – which has not been proven to exist – is needed to explain the extra positrons; and they wanted to understand how these positrons advance through the galaxy, which could yield clues as to their source. Though no existing model can explain how the positrons move through galactic space, Waxman and his group found a way to calculate the upper limit on the number of positrons that can be created and dispersed in the galaxy. Their model did not rely on the existence of any type of dark matter.

Recent data from another satellite mission – AMS – showed that the number of positrons at high energies comes close to the limit proposed by the Weizmann team, but does not exceed it. Analysis suggests that cosmic ray collisions in the interstellar gas can explain the existence of the positron stream, without involving dark matter. Armed with this knowledge, AMS is now gathering information on the emission of cosmic radiation out of the galaxy into intergalactic space.

 
Prof. Eli Waxman's research is supported by the Nella and Leon Benoziyo Center for Astrophysics, which he heads; and the Friends of the Weizmann Institute in memory of Richard Kronstein. Prof. Waxman is the incumbent of the Max Planck Professorial Chair of Quantum Physics.

 
 
 
Prof. Eli Waxman
Space & Physics
English
  • Dark matter
  • Eli Waxman
  • Particle Physics and Astrophysics
  • Positron

Getting to the Root of the Problem

English
 
 
colorful roots
 
Common wisdom has it that carrots are rich in vitamin A and tomatoes contain large amounts of lycopene, but reality is much more complicated: Plants contain thousands of substances called secondary metabolites. Their name notwithstanding, these substances are not secondary at all; they are involved in a host of vital processes, including gene control and interaction with the environment. Their functions include attracting pollinating insects and defending the plant against pests or too much sunlight. Luckily for humans, many of these substances also contribute to our health.

In the past few years, much effort has gone into identifying, mapping and monitoring secondary plant metabolites. Scientists use an approach called metabolomics: obtaining a general profile of various metabolites in a biological sample. This approach might help develop plants with a high concentration of metabolites that are useful for humans, or plants that are capable of fighting off pests more efficiently. Metabolic profiles make it possible to identify the genes and biochemical pathways involved in the production of these metabolites, and to increase or decrease the activity of these genes on demand. But despite the rapid progress in metabolomics technologies, scientists have until now had to make do with metabolic profiles of plants at a low resolution: They could determine the total quantity of metabolites in a particular plant tissue or organ, but not exactly in which types of cell these metabolites were found.

Weizmann Institute scientists, using an advanced metabolomics system, have now managed to increase this resolution substantially, determining the metabolic profiles of various cell types in plant roots. The study, reported in the Proceedings of the National Academy of Sciences, USA, was performed by Prof. Asaph Aharoni of the Institute’s Plant Sciences Department and his team: Drs. Arieh Moussaieff, Ilana Rogachev and Sergey Malitsky, and Merav Yativ, in collaboration with colleagues in Israel and abroad.

The scientists grew five types of plants, marking with a fluorescent dye particular cell types in their roots. They then sorted the root cells with the help of the fluorescent marker.

The study produced a comprehensive profile that revealed hundreds of substances, including those derived from three main chemical classes, distributed among different types of root cells. One of these groups, composed of a specific set of di-peptides, has been identified in roots for the first time. An analysis of the findings has also overturned an intuitive assumption: Metabolites were not necessarily found in the same cells that expressed the genes involved in their production. Apparently plants have a mechanism for moving substances to target areas.

Aharoni intends to increase the resolution of metabolic profiles even further, focusing on a particular group of root metabolites: plant hormones. A detailed mapping of materials in this group in root cells will make it possible, among other goals, to gain a better understanding of root development and growth, and to reveal how the root helps regulate the plant’s environment by releasing hormones into the surrounding soil.
 
Prof. Asaph Aharoni's research is supported by the Clore Center for Biological Physics; the Kahn Family Research Center for Systems Biology of the Human Cell; the Tom and Sondra Rykoff Family Foundation; Roberto and Renata Ruhman, Brazil; the Adelis Foundation; the Leona M. and Harry B. Helmsley Charitable Trust; the Minna James Heineman Stiftun; and the Raymond Burton Plant Genome Research Fund. Prof. Aharoni is the incumbent of the Peter J. Cohn Professorial Chair.


 
 
colorful roots
Environment
English
  • Asaph Aharoni
  • Metabolite
  • Metabolomics
  • Plant Genetics
  • Plant Sciences
  • Tomato

Seeking Solvation

English

(l-r) Profs. Irit Sagi and Martina Havenith at the opening ceremony for the launch of the Ruhr University Bochum’s Cluster of Excellence RESOLV

“Though water is one of life’s most essential, abundant and well-studied materials, the science behind its behavior and function is still poorly understood,” says Prof. Irit Sagi of the Weizmann Institute’s Biological Regulation Department. Sagi, a representative on the International Faculty Solvation Science, recently had the honor of opening the scientific section of the symposium marking the establishment of the new scientific discipline.


 “Solvation Science” is being launched under the auspices of a €28 million international consortium on water and spectroscopic science – the first of its kind – funded by the Deutsche Forschungsgemeinschaft (DFG). At its core is Germany’s Ruhr University Bochum’s Cluster of Excellence RESOLV (Ruhr Explores Solvation – solvents as active units), coordinated by Prof. Martina Havenith. International Faculty Solvation Science is a network of top institutions in the US, Europe, Asia and Israel, and it includes many of the high-profile scientists in the field.
 
 
RESOLV logo
 
Though solvation – the dissolving of a chemical substance in a liquid environment – is not new, the discovery that water plays an active role in the process is quite recent. Solvation is central to many important biological and industrial activities. The latter include pollution prevention, energy efficiency and corrosion, so gaining a deep understanding of this fundamental process is necessary to explain biological functions as well as develop key technologies. RESOLV aims to conduct fundamental research across various disciplines – biology, chemistry, materials science, engineering and computational biology – all based on the new perspective in which such solvents as water are active participants with functional roles in solvation, rather than the passive medium in which biological and chemical processes take place.

The pioneering work of Sagi, who is leading RESOLV’s biological projects, has already helped make great strides in this direction. The innovative, time-lapse, X-ray-based methods developed in her lab, combined with terahertz spectroscopy, enabled Sagi and her team, in collaboration with Havenith and Prof. Gregg Fields of the Torrey Pines Institute for Molecular Studies in Florida, to reveal in atomic detail what happens when water molecules interact with an active enzyme. This led to the breakthrough discovery that water plays a vital role in the actions of the enzyme, actively helping it to recognize the target site on a second protein.

An understanding of the precise role water plays in the actions of different types of biological molecules can, among other things, help harness the properties of water for the design of drugs, including some that Sagi’s team is in the process of developing, as well as improving high-throughput drug screening technology.

Included in RESOLV’s strategies for promoting the exchange of knowledge, people and ideas among leading scientists at all levels of their scientific careers in the field of solvation science is the establishment of various fellowship and student exchange programs, workshops and young faculties, with an emphasis on advancing women.

 
Prof. Irit Sagi’s research is supported by the Spencer Charitable Fund; the Leona M. and Harry B. Helmsley Charitable Trust; Cynthia Adelson, Canada; Dr. Mireille Steinberg, Canada; and the Leonard and Carol Berall Post Doctoral Fellowship. Prof. Sagi is the incumbent of the Maurizio Pontecorvo Professorial Chair.
 
(l-r) Profs. Irit Sagi and Martina Havenith at the opening ceremony for the launch of the Ruhr University Bochum’s Cluster of Excellence RESOLV
Space & Physics
English
  • Biological Regulation
  • Enzyme
  • International conference
  • Irit Sagi
  • Water

The Smell of White

English

 

Prof. Noam Sobel
 
You can see the color white; you can hear white noise. Now, Weizmann Institute researchers have shown that you can also smell a white odor. Their research findings appeared in the Proceedings of the National Academy of Sciences (PNAS).

 

The white we see is actually a mixture of light waves of different wavelengths. In a similar manner, the hum we call white noise is made of a combination of assorted sound frequencies. To be perceived as white, a stimulus must meet two conditions: The mix that produces them must span the range of our perception; and each component must be present in the same intensity. Could both of these conditions be met with odors?
 

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A research team in the Neurobiology Department, led by research student Tali Weiss and Dr. Kobi Snitz, both in the group of Prof. Noam Sobel, decided to take up the challenge. They began with 86 different pure scents (each made of a single type of odor molecule) spanning the entire “smell map,” carefully diluted them to obtain similar intensities and then created blends. Each blend contained a different mixture of odors from various parts of the smell map. These blends were then presented in pairs to volunteers, who were asked to compare the two.
white smell illustration
 
The team discovered that the more odors that were blended together in the paired mixtures, the more the subjects tended to rate them as similar – even though the two shared no common components. Blends that each contained 30 different odors or more were thought to be almost identical.

The researchers then created a number of such odor blends, giving them a nonsense name: Laurax. Once the subjects were exposed to one of the Laurax mixes and became accustomed to the smell, they were exposed to new blends – mixtures they had not previously smelled. They also called some of these new blends “Laurax,” but only if they contained 30 or more odors encompassing the range of possible smells. Mixtures of 20 scents or fewer were not thought to be Laurax. In other words, Laurax was a white smell. In a follow-up experiment, volunteers described it as being neutral – not pleasant, but not unpleasant.

“On the one hand,” says Sobel, “The findings expand the concept of ‘white’ beyond the familiar sight and sound. On the other, they touch on the most basic principles underlying our sense of smell, and these raise some issues with the conventional wisdom on the subject.” The most widely accepted view, for instance, describes the sense of smell as a sort of machine that detects odor molecules. But the Weizmann study implies that our smell systems perceive whole scents, rather than the individual odors they consist of.

Participating in the research were Adi Yablonka in the group of Prof. Noam Sobel and Dr. Elad Schneidman, also of the Neurobiology Department.
 
 
Prof. Noam Sobel's research is supported by the Nadia Jaglom Laboratory for the Research in the Neurobiology of Olfaction; the estate of Lore Lennon; the Adelis Foundation; the James S. McDonnell Foundation 21st Century Science; the  Scholar in Understanding Human Cognition Program; the Minerva Foundation; and the European Research Council.

 
 
 
 
white smell illustration
Life Sciences
English
  • Noam Sobel
  • Perception
  • Smell

Learning a New Sense

English
 

 

Prof. Ehud Ahissar
 
Rats use a sense that humans don’t: whisking. They move their facial whiskers back and forth about eight times a second to locate objects in their environment. At the Weizmann Institute, researchers had blindfolded volunteers learn to sense using artificial “whiskers.”  The findings, which appeared in the Journal of Neuroscience, have yielded new insight into the process of sensing, and they may point to new avenues in developing aids for the blind.

The scientific team, including Drs. Avraham Saig and Goren Gordon, and Eldad Assa in the group of Prof. Ehud Ahissar and Dr. Amos Arieli, all of the Neurobiology Department, attached a “whisker” – a 30-cm-long elastic “hair” with position and force sensors on its base – to the index finger of each hand of a blindfolded subject. Then two poles were placed at arm’s distance on either side and slightly to the front of the seated subject, with one a bit farther back than the other. Using just their whiskers, the subjects were challenged to figure out which pole was the back one. As the experiment continued, the displacement between front and back poles was gradually reduced.

Already on the first day of the experiment, subjects picked up the new sense so well that they could correctly identify a pole that was set back by only 8 cm, determining which pole was farther back because the whisker on that hand made contact earlier. In other words, the subjects figured the spatial information from the sensory timing.

When they repeated the testing the next day, the researchers discovered that the subjects had improved their whisking skills significantly: The average sensory threshold went down to just 3 cm, with some being able to sense a displacement of just 1 cm. Interestingly, the ability of the subjects to sense time differences had not changed over the two days. Rather, they had improved in the motor aspects of their whisking strategies: Slowing down their hand motions – in effect lengthening the delay time – enabled them to sense a smaller spatial difference.

Saig: “We know that our senses are linked to muscles: In order to sense the texture of cloth, for example, we move our fingers across it. In this research, we see that changing our physical movements alone can be sufficient to sharpen our perception.”

Ahissar: “Our findings reveal some new principles of active sensing and show us that activating a new artificial sense in a ‘natural’ way can be very efficient.”  Arieli adds: “Our vision for the future is to help blind people ‘see’ with their fingers. Small devices that translate video to mechanical stimulation, based on principles of active sensing that are common to vision and touch, could provide an intuitive, easily used sensory aid.”
 
Volunteers had "whiskers"attached to their fingers
               
 
 
 
 
 

Prof. Ehud Ahissar's research is supported by the Murray H. & Meyer Grodetsky Center for Research of Higher Brain Functions; the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Kahn Family Research Center for Systems Biology of the Human Cell; Lord David Alliance, CBE; the Berlin Family Foundation; Jack and Lenore Lowenthal, Brooklyn, NY; Research in Memory of Irving Bieber, M.D. and Toby Bieber, M.D.;the Harris Foundation for Brain Research; and the Joseph D. Shane Fund for Neurosciences. Prof. Ahissar is the incumbent of the Helen Diller Family Professorial Chair in Neurobiology.
 

 

 
 
Volunteers had "whiskers"attached to their fingers
Life Sciences
English
  • Ehud Ahissar
  • Perception
  • Whiskers

The Gene Control Hierarchy

English
 
 
Dr. Ido Amit
About 90% of the mutations that cause disease occur in short regulatory segments of the genome that sit next to the genes and determine whether a particular gene will be turned on, where and how strongly.
 
A research team led by Dr. Ido Amit of the Weizmann Institute Immunology Department, together with scientists from the Broad Institute in Massachusetts, including Manuel Garber, Nir Yosef and Aviv Regev, and Nir Friedman of the Hebrew University of Jerusalem, developed an advanced, automated system for mapping these sites, and then used it to uncover important principles of how these regulatory elements function. This system enabled a small team of researchers to produce results that rival the efforts of huge scientific consortiums, in a relatively short period of time.

Among other things, their study, which appeared recently in Molecular Cell, revealed that the actions of these regulatory factors can be neatly classified into three levels in a sort of regulatory hierarchy. In the bottom tier are those factors that create the rough divisions into main cell types by directing cell differentiation. These factors are the “basic identity” guides that can, on their own, determine whether a cell will have the characteristics of a muscle cell, a nerve cell, etc. On the second tier are the regulatory factors that determine a cell’s sub-identity, which they do by controlling the strength of a gene’s expression. These factors are in charge of producing closely-related sub-types, for instance, muscle fibers that are either smooth or striated, or closely-related immune cells. Regulatory factors in the third tier are even more specialized: They only affect the expression of certain genes that are called into action in response to signals from outside the cell: bacterial invasion, hormones, hunger pangs, etc.

Amit: “The new method for mapping the gene’s regulatory plan may open new vistas for investigating all sorts of biological processes, including the system failures that occur in disease.”
 
Dr. Ido Amit's research is supported by the Abramson Family Center for Young Scientists; the Abisch Frenkel Foundation for the Promotion of Life Sciences; Sam Revusky, Canada; the Leona M. and Harry B. Helmsley Charitable Trust; the M.D. Moross Institute for Cancer Research; Drs. Herbert and Esther Hecht, Beverly Hills, CA; the estate of Ernst and Anni Deutsch; and the estate of Irwin Mandel.
 




 
 
Dr. Ido Amit
Life Sciences
English
  • Gene code
  • Gene regulation
  • Ido Amit
  • Immune cells
  • Immunology
  • Personalized medicine

How Stem Cells Stay Young

English
 
Hiding deep inside the bone marrow, special cells wait patiently for the hour of need – infection, for example – at which point these blood-forming stem cells can proliferate and differentiate into billions of mature blood immune cells. But the body always maintains a reserve of undifferentiated stem cells for future crises. A research team headed by Prof. Tsvee Lapidot of the Institute’s immunology Department recently discovered a new type of bodyguard that protects stem cells from over-differentiation. In a paper that appeared in Nature Immunology, they revealed how this rare, previously unknown sub-group of activated immune cells keeps the stem cells in the bone marrow “forever young.”

Blood-forming stem cells live in comfort in the bone marrow, surrounded by an entourage of support cells that cater to their needs and direct their development – the mesenchymal cells. The research team, which included postdoctoral fellow Dr. Aya Ludin, Prof. Steffen Jung of the Immunology Department and his group, and Ziv Porat of the Biological Services Unit, discovered another type of support cell for the stem cells. These cells are an offshoot of the macrophage family, literally the “big eaters” of the immune system, which are important, for instance, for bacterial clearance. It is a rare sub-population of the bone-marrow macrophages that take stem cells under their wing and prevent differentiation.
 
Prostaglandins guard stem cells by increasing the production of an inhibitory factor in the mesenchymal bone marrow cells. Mesenchymal cells are marked with a green protein (left); the inhibitory factor is red (center). Combined image (right): Treatment with prostaglandins (bottom) increases the secretion of the inhibitory factor
 

 

 
The researchers revealed, in precise detail, how these macrophages guard the stem cells. They secrete substances called prostaglandins, which are absorbed by the stem cells. In a chain of biochemical events, these substances delay differentiation and preserve the youthful state of the stem cells. In addition, the prostaglandins work on the neighboring mesenchymal cells, activating the secretion of a delaying substance in them and increasing the production of receptors for this substance on the stem cells themselves. This activity, says Lapidot, may be what helps the non-dividing stem cells survive chemotherapy – a known phenomenon. Macrophages also live through the treatment, and they respond by increasing their prostaglandin output, thus heightening their vigilance in protecting the stem cells.
 
In previous work in Lapidot’s lab, it was discovered that prostaglandin treatments can improve the number and quality of stem cells. This insight is currently being tested by doctors in clinical trials for the use of stem cells transplanted from umbilical cord blood to treat adult leukemia patients. These trials are showing that prior treatment with prostaglandins improves the migration and repopulation potential, so that the small quantities of stem cells in cord blood can better cure the patients.
 
Prof. Steffen Jung's research is supported by the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Leir Charitable Foundations; the Leona M. and Harry B. Helmsley Charitable Trust; the Adelis Foundation; Lord David Alliance, CBE; the Wolfson Family Charitable Trust; the estate of Olga Klein Astrachan and the estate of Florence Cuevas.
 
Prof. Tsvee Lapidot's research is supported by the M.D. Moross Institute for Cancer Research; and the Leona M. and Harry B. Helmsley Charitable Trust. Prof. Lapidot is the incumbent of the Edith Arnoff Stein Professorial Chair in Stem Cell Research.


 
 
 

 
 
Prostaglandins guard stem cells by increasing the production of an inhibitory factor in the mesenchymal bone marrow cells. Mesenchymal cells are marked with a green protein (left); the inhibitory factor is red (center). Combined image (right): Treatment with prostaglandins (bottom) increases the secretion of the inhibitory factor
Life Sciences
English
  • Blood stem cell
  • Bone marrow
  • Immune cells
  • Immunology
  • Steffen Jung
  • Tsvee Lapidot

Living with Arsenic

English
 
Prof. Dan Tawfik, Dr. Mikael Elias, Korina Goldin and Alon Wellner
                 

 

 

 

 

 

 

 

Microorganisms living in environments that are naturally rich in the arsenic-based compound arsenate face a unique challenge: How to take up the phosphate compounds they need to live, while avoiding the toxic arsenate?

Chemically, arsenate is nearly indistinguishable from phosphate. “However,” says Prof. Dan Tawfik of the Biological Chemistry Department, “phosphate forms highly stable bonds in DNA and other key biological compounds, whereas bonds to arsenate are quickly broken. So how does a microorganism surrounded by arsenate distinguish between two molecules that are almost the same size and have identical shapes and ionic properties?”  

Tawfik, postdoctoral fellow Dr. Mikael Elias, Ph.D. student Alon Wellner and lab assistant Korina Goldin, in collaboration with Tobias Erb and Julia Vorholt of ETH Zurich, looked at a protein in bacteria that takes up phosphate. PBP (short for phosphate binding protein) sits near the bacteria’s outer membrane, where it latches onto phosphates and passes them on to pumps that transport them into the cell.
Bacteria in an arsenate-rich environment. Image: NASA
 
In research that recently appeared in Nature, the team compared the activity of several different PBPs – some, from bacteria such as E. coli that are sensitive to arsenate and others, such as those from an arsenic-rich environment that are tolerant of the chemical. While the PBPs in the ordinary bacterium were about 500 times more likely to bind phosphate than arsenate, in the arsenic-tolerant bacterium that factor jumped to around 5000. In other words, to cope with their toxic environment, the bacteria evolved a mechanism of extreme selectivity to ensure their supply of phosphate while keeping the arsenate out.

Elias then compared phosphate and arsenate binding by crystallizing PBPs along with one of the two compounds. But the initial comparison suggested that when arsenate bound to the protein, it did so in just the same way as phosphate. Elias suspected that the key might lie in a single, highly unusual bond between a hydrogen atom in the protein and the molecule.

To see the difference, the team had to stretch the limits of crystallization technology, getting the resolution to less than one angstrom – fine enough to identify individual hydrogen atoms and compare their bonds. Only then were they able to identify a single disparity: The angles of that unusual hydrogen bond were different. Inside a tight cavity within the PBP structure, phosphate binds at a “textbook angle,” according to Elias. The slightly larger arsenate molecule, on the other hand, gets pushed up against the hydrogen and bonds at an unnatural, distorted angle. That angle is likely to lead to repulsion between the molecule and other atoms in the cavity, preventing the PBP from passing arsenate into the cell’s interior.

Tawfik: “This first observation of a PBP discrimination mechanism is an exciting demonstration of the exquisite fine-tuning that enables proteins to distinguish between two nearly identical molecules.”
 
Prof. Dan Tawfik's research is supported by the Adelis Foundation; and the estate of Mark Scher. Prof. Tawfik is the incumbent of the Nella and Leon Benoziyo Professorial Chair.


 
 
Prof. Dan Tawfik, Dr. Mikael Elias, Korina Goldin and Alon Wellner
Life Sciences
English
  • Bacterial cells
  • Biological Chemistry
  • Dan Tawfik
  • Protein
  • X-ray crystallography

Immune Cells’ Flexible Choices

English
 

 

Dr. Nir Friedman
 
One of the mechanisms used by the immune system to cope with the huge variety of possible threats from viruses, bacteria and cancerous cells is to randomly combine DNA segments for the production of receptors on lymphocytes – a type of white blood cell. The number of possible receptors is almost inconceivably large – a one followed by 15 zeroes. Yet some receptors are produced at a higher rate than mere chance would dictate. New research at the Weizmann Institute can help explain how the immune system maintains its complexity while giving preference to certain receptors.

The research team headed by Dr. Nir Friedman, including postdoctoral fellows Drs. Wilfred Ndifon and Hilah Gal, together with Prof. Ruth Arnon and Dr. Rina Aharoni, all of the Immunology Department, looked at the DNA sequences in T lymphocytes for the receptors that identify disease agents. The genetic sequences encoding these receptors are each composed of three random DNA segments – something like the random lineups in a slot machine. Each of those segments is taken from a different area of the lymphocyte cell genome, and each area has a full “menu” of segments to choose from. To assemble the sequence, the DNA strand folds, bringing a segment from the first area close to those in the second and third areas. The sequence is then cut and pasted together and the excess bits of DNA in between discarded, thus creating a new and unique genetic sequence for the receptors in each lymphocyte cell.

In a study that appeared recently in the Proceedings of the National Academy of Sciences (PNAS), the team used a system they developed, based on advanced high-throughput sequencing techniques, to investigate the genetic sequences of an entire array of lymphocyte receptors in mice. With this “panoramic view,” the researchers were able to assess how widespread each receptor was and even to suggest a reason for their uneven distribution. It appears that the secret is in the pieces of DNA that eventually get discarded: Both the length of these segments and their flexibility – a function of the protein “packaging” that gives them their shape – determine how likely it is that two distant segments will meet.

The researchers then looked at small groups of individuals – up to five – to see if they could find common lymphocyte receptor sequences among them. Surprisingly, the team discovered that a group of five was more likely to all share a common sequence than were smaller sub-groups. That may seem like saying there is a higher chance of winning at the slot machine five times in a row than just twice.  But the scientists can explain: The common sequences may be situated in the genome in such a way that they are more likely to be integrated into the receptor sequences. These may have been selected by evolution for their ability to fight common disease agents or prevent autoimmune disease.

Prof. Ruth Arnon's research is supported by the Leona M. and Harry B. Helmsley Charitable Trust.
 
Dr. Nir Friedman's research is supported by the Victor Pastor Fund for Cellular Disease Research; the Abraham and Sonia Rochlin Foundation; the Adelis Foundation; the Norman E. Alexander Family Foundation; the Nella and Leon Benoziyo Center for Neurological Diseases; the Clore Center for Biological Physics; the Jeanne and Joseph Nissim Foundation for Life Sciences Research; the Crown Endowment Fund for Immunological Research; the estate of John Hunter; and the estate of Suzy Knoll. Dr. Friedman is the incumbent of the Pauline Recanati Career Development Chair.

 

 
 

 

Dr. Nir Friedman
Life Sciences
English
  • DNA
  • Gene code
  • Immune cells
  • Immunology
  • Nir Friedman
  • Ruth Arnon

Switches for Stem Cells

English
(l-r) Prof. Eytan Domany, Dr. Jacob Hanna, Rita Versterman, Gilad Fuchs and Prof. Moshe Oren
 
Stem cells hold great promise for the medicine of the future, but they can also be a cause of disease. When these self-renewing, unspecialized cells fail to differentiate into diverse cell types, they can start dividing uncontrollably, leading to cancer. A Weizmann Institute-led study, published in Molecular Cell, reveals a potential molecular mechanism behind this link.

The scientists managed to uncover the details of a step in the process of DNA “repackaging” that takes place during embryonic stem cell differentiation. It turns out that for the cells to differentiate properly, certain pieces of the packaging of their DNA must be labeled by a molecular tag called ubiquitin. The researchers identified two switches: An enzyme called RNF20 enhances the tagging, whereas a second enzyme, USP44, does the opposite, shutting it down. They found that both these switches must operate properly for the differentiation process to proceed efficiently. When the scientists interfered with the tagging – either by disabling the “ON” switch RNF20, or by deregulating the activity of the “OFF” switch USP44 – the stem cells failed to differentiate.
 
These experiments might explain the significance of molecular defects identified in a number of cancers, for example, the abnormally low levels of RNF20 in certain breast and prostate cancers, and the excess of USP44 in certain leukemias. 
Stem cells (alkaline phosphatase staining) from the lab of Dr. Jacob Hanna
 
This research was led by Prof. Moshe Oren of the Molecular Cell Biology Department, with Prof. Eytan Domany of the Physics of Complex Systems Department and Dr. Jacob Hanna of the Molecular Genetics Department. The team included Weizmann Institute’s Gilad Fuchs, Efrat Shema, Rita Vesterman, Eran Kotler, Sylvia Wilder, Lior Golomb, Ariel Pribluda and Ester Feldmesser, as well as Zohar Wolchinsky of the Technion – Israel Institute of Technology, Feng Zhang and Xiaochun Yu of the University of Michigan in the US, Mahmood Haj-Yahya and Ashraf Brik of Ben-Gurion University of the Negev, and Daniel Aberdam of the Technion and the University of Nice-Sophia Antipolis in France.
 
Prof. Eytan Domany’s research is supported by the Kahn Family Research Center for Systems Biology of the Human Cell, which he heads; the Mario Negri Institute for Pharmacological Research - Weizmann Institute of Science Exchange Program; the Leir Charitable Foundations; and Mordechai Segal, Israel. Prof. Domany is the incumbent of the Henry J. Leir Professorial Chair.
 
Dr. Jacob Hanna’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; Pascal and Ilana Mantoux, France/Israel; the Sir Charles Clore Research Prize; Erica A. Drake and Robert Drake; and the European Research Council.

Prof. Moshe Oren’s research is supported by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Robert Bosch Foundation; the estate of Harold Z. Novak; and the European Research Council. Prof. Oren is the incumbent of the Andre Lwoff Professorial Chair in Molecular Biology.
 
 
Stem cells (alkaline phosphatase staining) from the lab of Dr. Jacob Hanna
Life Sciences
English
  • Cancer
  • Eytan Domany
  • Jacob Hanna
  • Molecular Cell Biology
  • Molecular Genetics
  • Moshe Oren
  • Physics of Complex Systems
  • Stem cell

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