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  • richardmitnick 11:20 am on December 4, 2016 Permalink | Reply
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    From Weizmann: “When Cells Are Fit” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    07.11.2016 [I guess this has just ben in hiding.]
    No writer credit found

    How do the expression levels of numerous proteins affect a cell’s fitness?

    Tracking protein activity levels in a cell is essential to the study of such diseases as cancer which, alongside changes in the genes, involves changes in the activity levels of numerous proteins. However, deducing function, fitness and cellular well-being from the growing number of protein level measurements is still a major challenge. For example, is a two-fold – or 100-fold – range in activity for a particular protein tolerable over the population, or does it herald differences in the way that the cells carry out their tasks? Charting this connection could transform the way we diagnose, monitor and treat patients.

    1
    (l-r) Maya Lotan-Pompan, Leeat Yankielowicz Keren and Prof. Eran Segal can now look at multiple protein expression levels at once

    “Most experiments examining ranging protein activity levels have, until now, focused on single proteins. What we did was to develop a way to systematically vary activity levels for hundreds of different proteins – all in a single experiment – and accurately measure how this affects the function of the cells,” says Leeat Yankielowicz Keren, a research student in the group of Prof. Eran Segal of the Computer Science and Applied Mathematics, and Molecular Cell Biology Departments at the Weizmann Institute of Science.

    The basic idea of the experiment in Segal’s lab was to create a competition in which common bakers’ yeast cells are pitted against one another. Each cell was nearly identical to its neighbors, except for a tweak to the activity level of one of its proteins. Thousands of these genetically engineered yeast cells were grown together in lab dishes; the “winners” were those in which expression levels boosted their fitness, basically enabling the yeast to eat more, grow and divide faster.

    Segal and his group developed a high-throughput genetic engineering technique that enabled them to manipulate the activity levels of different protein levels within thousands of cells simultaneously, precisely controlling, for each, the amounts of one particular protein. With 130 different activity levels – the highest 500 times the lowest – attached to 81 different protein-encoding sequences, the researchers created something like 10,000 different variations on the basic yeast cell, assigning each a “barcode” for convenient identification. With a combination of DNA sequencing techniques and an algorithm they created to reconstruct the growth rates of the various yeast cells, the team was then able to accurately map the connections between protein levels and the fitness of the cell.

    The competition took place in two different “arenas.” In one, the yeast were fed the glucose sugar they prefer; in the second, they were fed a different kind of sugar, galactose. The team found that when the competition took place on the kind of sugar it prefers, the original, untouched version of the yeast cell was the overall winner – testimony to the efficiency of evolution. But on the second kind of sugar, others came out on top. These results showed that around 20% of the yeast’s natural protein activity levels are too low or too high for growing on this sugar. This could be relevant to biotechnology: The second sugar is cheaply and abundantly found in seaweed, and the yeast break it down into ethanol, which can be burned in place of fossil fuels. The study suggests that genetically engineering yeast to alter some of these protein levels could significantly increase the efficiency of this process.

    Mapping all the activity patterns together enabled the group to begin to see patterns in the chaos. Similar activity patterns, for example, pointed to proteins that work together. Further analysis even revealed the “math” that cells use to produce these proteins in the right ratios, for example, for the construction of complexes that require exact proportions of their various proteins.

    Some of the proteins appeared to operate in a very narrow range – levels even a bit below or above this range drastically affected the fitness of the yeast. Others seemed to be much more flexible – a little or a lot did not affect the cell’s fitness, at least for the particular growing conditions. Those showing the larger ranges in the fitness competition turned out to be proteins that ordinarily vary widely from cell to cell in the natural yeast population. These findings suggest that understanding this flexibility can shed light on how activity levels are selected in evolution.

    2
    Gene fitness profiles are different when yeast are grown on a sugar they normally prefer less

    For Segal and his team, the future goal is to create similar maps for protein activity levels in human cells. Such maps could form the basis of future diagnostic techniques that would be much more refined and precise than those of today, based on blood tests that already exist or can easily be developed. They might reveal the effects of diet or medications; and they could provide early diagnosis of cancer. Keren: “We want to eventually create a ‘chart’ that doctors can use to know which protein levels to check, and what levels should, ideally, be appearing in order to prevent disease.”

    Also participating in this study were Maya Lotan-Pompan and Dr. Adina Weinberger of Prof. Segal’s group, Dr. Jean Hausser and Prof. Uri Alon of the department of Molecular Cell Biology and Prof. Ron Milo of the department of Plant and Environmental Sciences.

    Science paper:
    Massively Parallel Interrogation of the Effects of Gene Expression Levels on Fitness, Cell

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 10:42 am on September 19, 2016 Permalink | Reply
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    From Weizmann: “Israeli Instrument Bound for Jupiter” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    07.01.2016 [This just appeared in social media.]
    No writer credit found

    Sometime in the year 2030, if all goes according to plan, some dozen groups around the world will begin receiving unique data streams sent from just above the planet Jupiter. Their instruments, which will include a device designed and constructed in Israel, will arrive there aboard the JUICE (JUpiter ICy satellite Explorer) spacecraft, a mission planned by the European Space Agency (ESA) to investigate the properties of the Solar System’s largest planet and several of its moons.

    ESA JUICE
    esa-juice-spacecraft
    ESA JUICE

    Among other things, the research groups participating in JUICE hope to discover whether the conditions for life exist anywhere in the vicinity of the planet.

    “This is the first time that an Israeli-built device will be carried beyond the Earth’s orbit,” says Dr. Yohai Kaspi of the Weizmann Institute’s Earth and Planetary Sciences Department, who is the principal investigator on this effort. The project, conducted in collaboration with an Italian team from the University of Rome, is called 3GM (Gravity & Geophysics of Jupiter and Galilean Moons).

    The Israeli contribution to the project is an atomic clock that will measure tiny vacillations in a radio beam provided by the Italian team. This clock must be so accurate it would lose less than a second in 100,000 years, so Kaspi has turned to the Israeli firm AccuBeat, which manufactures clocks that are used in high-tech aircraft, among other things. Its engineers, together with Kaspi and his team, including Dr. Eli Galanti and Dr. Marzia Parisi, have spent the last two years in research and development to design a device that should not only meet the strict demands of the experiment but survive the eight-year trip and function in the conditions of space. Their design was recently approved for flight by the European Space Agency. Israel’s Ministry of Science and Technology will fund the research, building and assembly of the device.

    For around two and a half years as JUICE orbits Jupiter, the 3GM team will investigate the planet’s atmosphere by intercepting radio waves traveling through the gas, timing them and measuring the angle at which the waves are deflected. This will enable them to decipher the atmosphere’s makeup.

    During flybys of three of the planet’s moons – Europa, Ganymede and Callisto – the 3GM instruments will help search for tides. Researchers observing these moons have noted fluctuations in the gravity of these moons, suggesting the large mass of Jupiter is creating tides in liquid oceans beneath their hard, icy exteriors. By measuring the variations in gravity, the researchers hope to learn how large these oceans are, what they are made of, and even whether their conditions might harbor life.

    The JUICE teams are preparing for a launch in 2022. That gives them three years to get the various instruments ready and another three to assemble and test the craft. In the long wait – eight years – from launch to arrival, Kaspi intends to work on building theoretical models that can be tested against the data they will receive from their instruments.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 11:35 am on July 3, 2016 Permalink | Reply
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    From Weimann: “Straight to the Gut” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    16.06.2016 [This just made it to social media.]
    No writer credit found

    Stem cells must get oriented before taking on new properties

    1
    (l-r) Julian Nicenboim, Lihee Asaf, Dr. Karina Yaniv and Dr. Gideon Hen explain how lymph stem cells get their signals straight. No image credit

    Understanding what makes these adult stem cells tick is a difficult undertaking: They can be hard to find, and each type may respond to several different signals and operate by different sets of rules. So when Yaniv and her group in the Weizmann Institute of Science’s Biological Regulation Department discovered, a year ago, that the body has a special store of stem cells that differentiate into lymphatic vessels, they were able to solve a 100-year old disagreement about the origins of the lymph system. But their findings also enabled them to grow lymph cells in lab cultures for the first time.

    This advance led to a new study, recently reported in Development, which sheds new light on what else these “special” stem cells can do, and how they do it. Yaniv, postdoctoral fellow Gideon Hen and research student Julian Nicenboim focused on the cells called endothelial cells that build blood vessel walls. “The endothelial cells in the blood vessels of the brain are very different from those found in the liver or kidneys. What tells these cells to adopt the characteristics of one or the other?”

    The researchers added fluorescent markers to the developing blood vessels of zebrafish embryos; these markers can switch their color from green to red under ultraviolet light. This enabled the team to trace the differentiation of living cells under the microscope over the course of several days.

    The group followed the fate of the previously identified stem cells, finding that they also give rise to the vasculature of the digestive system. In contrast to the cells that differentiate into adult lymph cells, those bound for the liver, intestinal or pancreatic blood vessels have a special set of signals − proteins in two families known as BMP and VEGF − to guide them on their way. The scientists discovered that these proteins are expressed for only a short period of time, and they first enable the cells to exit their protected “niche.” Only once these cells are pointed toward the proper organ can they begin to take on the properties required for the particular blood vessel of their final destination.

    2
    Blood vessels of a zebrafish embryo (red). The nuclei of the endothelial cells in these vessels are labeled in yellow, allowing researchers to track cell migration during development. The arrow indicates migration of cells arising from a blood vessel. Such cells arise from a pool of stem cells, and will give rise to blood vessels of the intestine, liver and the pancreas. No image credit.

    Yaniv says that these findings may shed light on another mystery: Where do cancerous or otherwise pathological blood cells come from? Such cells have supercharged capacities for differentiation and migration, leading to the suspicion that the “special” stem cells could be the source. Yaniv and her group are presently conducting research on adult zebrafish, tracking the new stem cell population in hopes of gaining deeper insight into their functions and malfunctions in the adult system.

    Dr. Karina Yaniv’s research is supported by the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Adelis Foundation; and the estate of Georges Lustgarten. Dr. Yaniv is the incumbent of the Louis and Ida Rich Career Development Chair.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 8:26 am on January 18, 2016 Permalink | Reply
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    From Weizmann: “Your Symptoms? Evolution’s Way of Telling You to Stay Home” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    07.01.2016
    No writer credit

    Temp 1
    No image credit

    When you have a fever, your nose is stuffed and your headache is spreading to your toes, your body is telling you to stay home in bed. Feeling sick is an evolutionary adaptation according to a hypothesis put forward by Prof. Guy Shakhar of the Weizmann Institute’s Immunology Department and Dr. Keren Shakhar of the Psychology Department of the College of Management Academic Studies, in a recent paper published in PLoS Biology.

    We tend to take it for granted that infection is what causes the symptoms of illness, assuming that the microbial invasion directly impinges on our well-being. In truth, many of our body’s systems are involved in being sick: the immune system and endocrine systems, as well as our nervous system. Moreover, the behavior we associate with sickness is not limited to humans. Anyone who has a pet knows that animals act differently when they are ill. Some of the most extreme “sickness behavior” is found in such social insects as bees, which typically abandon the hive to die elsewhere when they are sick. In other words, such behavior seems to have been preserved over millennia of evolution.

    The symptoms that accompany illness appear to negatively affect one’s chance of survival and reproduction. So why would this phenomenon persist? Symptoms, say the scientists, are not an adaptation that works on the level of the individual. Rather, they suggest, evolution is functioning on the level of the “selfish gene.” Even though the individual organism may not survive the illness, isolating itself from its social environment will reduce the overall rate of infection in the group. “From the point of view of the individual, this behavior may seem overly altruistic,” says Dr. Keren Shakhar, “but from the perspective of the gene, its odds of being passed down are improved.”

    In the paper, the scientists go through a list of common symptoms, and each seems to support the hypothesis. Appetite loss, for example, hinders the disease from spreading by communal food or water resources. Fatigue and weakness can lessen the mobility of the infected individual, reducing the radius of possible infection. Along with the symptoms, the sick individual can become depressed and lose interest in social and sexual contact, again limiting opportunities to transmit pathogens. Lapses in personal grooming and changes in body language say: I’m sick! Don’t come near!

    “We know that isolation is the most efficient way to stop a transmissible disease from spreading,” says Prof. Guy Shakhar. “The problem is that today, for example, with flu, many do not realize how deadly it can be. So they go against their natural instincts, take a pill to reduce pain and fever and go to work, where the chance of infecting others is much higher.”

    The scientists have proposed several ways of testing this hypothesis, but they also hope its message sinks in: When you feel sick, it’s a sign you need to stay home. Millions of years of evolution are not wrong.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 5:52 pm on January 13, 2016 Permalink | Reply
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    From Weizmann: “Weizmann Institute Drug, TOOKAD® Soluble, Approved for Prostate Cancer Therapy in Mexico” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    04.01.2016
    No writer credit found

    A successful Phase III clinical trial in Latin America confirmed the high rate of local cures and minimal side effects already reported in Phase II clinical trials

    Temp 1
    Magnetic resonance images of the prostate gland after treatment with Tookad Soluble. The black regions show the portions of the prostate that have been eliminated to remove the previously detected cancerous tissue

    A therapy invented at the Weizmann Institute of Science and clinically developed in collaboration with Steba Biotech (Luxembourg) has been approved by Cofepris, Mexico’s health authority, for the focal treatment of early-stage prostate cancer.

    The therapy involves a laser and a novel drug, TOOKAD® Soluble. A successful Phase III clinical trial in Latin America (Mexico, Peru and Panama), involving 80 patients, confirmed the high rate of local cures and minimal side effects already reported in Phase II clinical trials, as evidenced by negative biopsies and maintenance of patients’ potency, continence and overall quality of life.

    The marketing approval in Mexico comes in the wake of the recent completion of a second Phase III clinical trial in Europe. This randomized pivot study compared disease progression, cancer-free rate and urinary and erectile functions in patients treated with TOOKAD® Soluble and those undergoing active surveillance with a follow-up of two years. It involved more than 400 patients at 43 hospitals in 11 European countries and is currently under evaluation by the European Medicines Agency (EMA).

    The approved therapy follows a new paradigm developed by Prof. Yoram Salomon of the Biological Regulation Department and Prof. Avigdor Scherz of the Plant and Environmental Sciences Department in the framework of photodynamic therapy. It comprises an intravenous infusion of TOOKAD® Soluble, immediately followed by near-infrared laser illumination through thin optic fibers that are inserted into the cancer prostatic tissue, under ultrasound control. Tookad® Soluble was first synthesized in Scherz’s lab from bacteriochlorophyll, the photosynthetic pigment of certain aquatic bacteria that draw their energy supply from sunlight. The drug stays in the patient’s blood circulation until it totally clears 3-4 hours later, and it shows no toxicity. Confined illumination of the diseased tissue activates the circulating drug locally, resulting in the extensive generation of short-lived toxic molecules: oxygen and nitric oxide radicals. These highly reactive molecules initiate rapid occlusion and destruction of the tumor blood vessels, followed by necrotic death of the entire tumor while sparing nearby structures and their functions. The use of near-infrared illumination, together with the rapid clearance of the drug from the body and the unique non-thermal mechanism of action, makes it possible to safely treat large, deeply embedded cancerous tissue using a minimally invasive procedure. The recent marketing approval was provided to both the drug (TOOKAD® Soluble) and the laser illumination device (Laser), together designated Vascular Targeted Photodynamic Therapy (VTP) with TOOKAD® Soluble.

    In the currently approved focal therapy setting, TOOKAD® Soluble VTP (TS-VTP) is a day-case procedure lasting approximately 90 minutes. Patients are released a few hours later and can return to normal activities within a few days, with none of the side effects frequently associated with prostate removal by surgery or radiotherapy. This new minimally invasive technology offers a good alternative to patients diagnosed with early-stage prostate cancer. The number of these patients has dramatically increased in the last two decades due to widespread screening relying on levels of prostate specific antigen (PSA). This population faces the dilemma of undergoing the radical treatment of prostate removal with the risk of high morbidity, or remaining under active surveillance with increased risk of further cancer progression.

    Tookad® Soluble answers an unmet need in providing this category of patients with an appropriate treatment, which combines good efficacy with a preservation of the quality of life.

    Weizmann institute and Steba Biotech are currently pursuing an extensive oncological research program in collaboration with several clinical groups at Memorial Sloan Kettering Cancer Center in New York City. Four clinical studies for more advanced prostate cancer and other oncological indications stemming from this research are scheduled to start in 2016.

    Yeda Research and Development Company, the Weizmann Institute’s technology transfer arm, has licensed the drug to Steba Biotech, which manufactures Tookad Soluble. Amir Naiberg, CEO of Yeda: “Our cooperation with Steba covers 20 years of fruitful collaboration. The commitment made by the shareholders of Steba and their personal relationship and effective collaboration with Weizmann Institute scientists and Yeda, have enabled this tremendous accomplishment.”

    Prof. Yoram Salomon’s research is supported by the Principal Anstalt. Prof. Salomon is a Prof. Emeritus at the Weizmann Institute. He was the incumbent of Charles and Tillie Lubin Professorial Chair for Biochemical Endocrinology until his retirement in 2009. From the start Yoram and Avigdor acted jointly as principal investigators in collaborative research supported by numerous agencies. Since 2009 Prof. Salomon is a consultant in these projects.

    Prof. Avigdor Scherz’s research is supported by the Leona M. and Harry B. Helmsley Charitable Trust; the Thompson Family Foundation, Inc.; the Principal Anstalt; and Sharon Zuckerman, Canada. Prof. Scherz is the incumbent of the Robert and Yadelle Sklare Professorial Chair in Biochemistry.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 6:44 am on October 26, 2015 Permalink | Reply
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    From Weizmann: “Awakenings” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    10.26.15

    1
    Prof. Atan Gross revealed a mechanism for waking up sleeping stem cells

    An energy supply is important for any undertaking; but in stem cells, energy-producing structures sometimes determine the very fate of the cell. A new Weizmann Institute study, reported in Nature Communications, reveals how cellular power plants called mitochondria can wake up blood-forming stem cells from their sleep, causing them to proliferate and mature into different cell types.

    Blood-forming stem cells, which give rise to the entire immune system, lie sleeping in niches in the bone marrow. They are continuously woken up to replenish the blood with mature cells, which have a finite life span. The wake-up call can come in the form of reactive oxygen molecules called free radicals, which are produced in the mitochondria as a byproduct of the manufacture of cellular fuel. A team of Weizmann Institute scientists headed by Prof. Atan Gross of the Biological Regulation Department has now discovered a mechanism by which the wake-up message is sent to these stem cells via their mitochondria.

    2
    Mitochondria (dark gray), viewed under an electron microscope, are significantly enlarged in blood-forming stem cells lacking MTCH2 (right) compared with regular blood-forming stem cells (left)

    The heart of the message is a protein known as MTCH2 – or “Mitch,” as the scientists call it – which sits on the membranes of mitochondria and acts as a molecular switch. When Gross discovered MTCH2 more than a decade ago, he and his team showed that this protein can regulate cell suicide: Under conditions of severe stress, “Mitch” conveys a self-destruct message that prompts the mitochondria to develop holes and disintegrate, ultimately causing the cell to die. In the new study, postdoctoral fellow Dr. Maria Maryanovich and other members of Gross’s lab – Dr. Yehudit Zaltsman and PhD students Antonella Ruggiero and Andres Goldman – found that in blood-forming stem cells, MTCH2 has an additional role: It suppresses the activity of the mitochondria for as long as the cells need to remain in their dormant state.

    When the scientists created genetically engineered mice that lacked MTCH2 throughout their blood system, the mitochondria in the blood-forming stem cells underwent major changes. These organelles more than doubled in size, and their activity increased almost four-fold. As a result, the stem cells became activated, apparently woken from their sleep by the free radicals generated in the hyper-busy mitochondria. The cells left their niches and began to mature in such large numbers that their supply in the bone marrow was exhausted. These findings suggest that enhancing the activity of the mitochondria – by decreasing MTCH2 – can awaken the stem cells when needed.

    This clever control mechanism of the stem cell cycle – awakening the cells by enhancing their metabolism – ensures that the cells have sufficient energy for growing and maturing. “Like travelers waking up in the morning and stocking up on essential provisions before undertaking a long journey, sleepy stem cells need the energy to survive their new journey after they awaken,” says Gross. “We found that turning on mitochondria metabolism supplies the cells with precisely such energy.” Taking part in the study were Dr. Smadar Levin Zaidman of Chemical Research Support, Dr. Ziv Porat of the Biological Services Unit, and Prof. Tsvee Lapidot and Dr. Karin Golan of the Immunology Department.

    3
    A three-dimensional reconstruction of the mitochondrial volume: The volume is larger (yellow and red) in blood-forming stem cells lacking MTCH2 (right), and relatively smaller (blue and green) in regular blood-forming stem cells

    In addition to shedding new light on the basic biology of the stem cell cycle, the Weizmann Institute study may lead to new ways of controlling the activity of stem cells in research as well as in the clinic. The findings suggest that it may be possible to awaken stem cells by altering their metabolism, rather than by manipulating their genes, as is done today. In addition, the findings open up a new avenue of research into leukemia. They suggest that defects in the control of cellular metabolism in blood-forming stem cells at various stages of their maturation may lead to the abnormal cellular proliferation observed in leukemia. If this is indeed found to be the case, it may be possible to treat leukemia by correcting the cells’ metabolic defects.

    Prof. Atan Gross’s research is supported by the Yeda-Sela Center for Basic Research; the Adelis Foundation; the Lubin-Schupf Fund for Women in Science; the Pearl Welinsky Merlo Foundation Scientific Progress Research Fund; the Louis and Fannie Tolz Collaborative Research Project; the Hymen T. Milgrom Trust donation fund; the Rising Tide Foundation; Lord David Alliance, CBE; the estate of Tony Bieber; and the estate of John Hunter. Prof Gross is the incumbent of the Marketa and Frederick Alexander Professorial Chair.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

    Stem Education Coalition

    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 8:53 am on October 20, 2015 Permalink | Reply
    Tags: , , , Weizmann Institute of Science   

    From Weizmann: “Melanoma Mutations Mapped” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    06-07-2015
    No Writer Credit

    Cancer is a disease that begins with gene alterations: At the high end of the mutation scale, a cancer such as melanoma has hundreds. That may be why melanoma drugs that block certain cancer-causing genes only work for a subset of patients, and even these are successful for just a short while. Better maps might help in navigating the complex routes that mutations chart in cancer cells. To this end, a giant consortium of scientists has been working on the Cancer Genome Atlas, a project overseen by the US National Institutes of Health, to plot the maps of a number of cancer genomes.

    1
    Prof. Yardena Samuels

    Prof. Yardena Samuels of the Weizmann Institute’s Molecular Cell Biology Department is a part of the Cancer Atlas group that recently produced the melanoma genome map. Hundreds of researchers from Australia, the US, Canada, Russia, Germany, Italy, Poland, China and Korea participated in the effort. “This has been the most in-depth mapping yet,” says Samuels. After a careful selection process, 333 melanoma samples were included in the study, and the screening was conducted using six different platform technologies, going beyond the bounds of simple gene sequencing to explore how the various genes are expressed, how they interact and which proteins they produce.

    Each sample required a second, non-cancerous sample from the same patient for comparison, and several of the samples afforded comparisons of genes from the patients’ early tumors to those that had metastasized. In addition to the sequencing of protein-coding genes, some of the samples had their entire genome sequenced, which could prove in the future to be an “unexplored goldmine of information on what makes cancer tick,” says Samuels. RNA and microRNA, as well as protein expression assays, were included. The latter screens added further dimensions to the gene map – creating a “landscape” that can help researchers understand not just the genes, but the pathways, intersections and cancer-causing diversions associated with them.

    “The study was intensive, and it has paid off,” says Samuels. For one thing, it showed, for the first time, that melanomas can be divided into four distinct groups, according to a main mutation. Now melanoma researchers will be able to focus on understanding exactly how the different mutations lead to cancer, and physicians may eventualy gain better tools for diagnosing the disease and tailoring treatments to individual cases. The first type, occurring in a mutation “hotspot,” is known as BRAF, and it tends to appear in younger people, in whom the cancer is fairly aggressive. The second is known as RAS. BRAF and RAS protein products lie in the same pathway so that BRAF and RAS mutations are mutually exclusive: A patient will have one or the other, but not both. The third is called NF1, and this mutation was found in older patients. The fourth group, called triple wild type, had none of the three most common mutations.

    2
    Metastatic melanoma cells. Image: NIH

    In addition, the in-depth analysis held a surprise finding. RNA and protein expression tests revealed the infiltration of immune cells called lymphocytes into the tumors. These turned out to be highly correlated with the patient’s prognosis – the more lymphocytes, the better their chances of surviving, regardless of the genetic signature of their melanoma cells. This finding has interesting implications for the field of cancer immunotherapy, in which a patient’s immune cells are “trained” to fight the cancer. It suggests that even upping the numbers of particular immune cells could have a positive effect, and it could help identify those patients who might benefit from various new immunotherapies.

    Another area of research arising from the new cancer genome that could bear fruit in the near future is a sort of “matching” of existing drug compounds to the genetic profiles. For example, a comparison of genomes from different cancers shows that the genetic mutation pattern of one type of melanoma is similar to that of a form of a brain cancer called glioblastoma. That means that drugs already on the market for glioblastoma might have an effect on melanoma as well.

    Separating the drivers from the passengers

    Samuels says she intends to continue adding detail to the map – her lab has its own bank of melanoma cells, and she is creating an expanded database of melanoma genomes. This melanoma cell bank is an important resource for her lab, where she and her group are working to figure out which of the many mutated genes drive the development of melanoma, which help the drivers “steer,” and which are just “passengers.” Experiments on cell lines from the bank, for example, enable the group to investigate the effects of individual genes, and they are going after are suspected drivers, as well as the “helpers.”

    In parallel, she is beginning to explore the pathways – the series of biological interactions that underlie each action in the cell – in two of the melanoma subgroups. “If the mutation in a gene, for example, a tumor suppressor, causes a loss of function, you can’t fix it by blocking the gene – the problem is that the gene is not working in the first place,” she says. “But if you follow the pathway, you are likely to find other genes that present targets for turning the pathway around, farther down the line.

    “We are entering a new era of precision medicine in melanoma, in which physicians will aim to determine the personal profile of each cancer and tailor the treatment accordingly,” she says

    Prof. Yardena Samuels’ research is supported by the Ekard Institute for Diagnosis, which she heads; the Henry Chanoch Krenter Institute for Biomedical Imaging and Genomics; the Laboratory in the name of M.E.H. Fund established by Margot and Ernst Hamburger; the Louis and Fannie Tolz Collaborative Research Project; the Dukler Fund for Cancer Research; the European Research Council; the De Benedetti Foundation-Cherasco 1547; the Peter and Patricia Gruber Awards; the Comisaroff Family Trust; the Rising Tide Foundation; the estate of Alice Schwarz-Gardos; the estate of John Hunter; the Estate of Adrian Finer. Prof. Samuels is the incumbent of the Knell Family Professorial Chair.

    See the full article here .

    Please help promote STEM in your local schools.

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 6:46 am on October 15, 2015 Permalink | Reply
    Tags: , , Circadian clocks, Weizmann Institute of Science   

    From Weizmann: “Natural Metabolite Might Reset Aging Biological Clocks” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    12 Oct 2015
    No Writer Credit

    1

    Weizmann Institute researchers show that our daily rhythms are governed by a substance that declines with age

    As we age, our biological clocks tend to wind down. A Weizmann Institute research team has now revealed an intriguing new link between a group of metabolites whose levels drop as our cells age and the functioning of our circadian clocks – mechanisms encoded in our genes that keep time to cycles of day and night. Their results, which appeared in Cell Metabolism, suggest that the substance, which is found in many foods, could possibly help keep our internal timekeepers up to speed.

    Dr. Gad Asher’s lab in the Weizmann Institute’s Biological Chemistry Department investigates circadian clocks, trying to understand how these natural timekeepers help regulate, and are affected by, everything from nutrition to metabolism. In the present study, he and his research student Ziv Zwighaft were following clues that certain metabolites called polyamines could be tied to the functioning of circadian clocks. We get polyamines from food, but our cells manufacture them as well. These substances are known to regulate a number of essential processes in the cell, including growth and proliferation. And the levels of polyamines have been found to naturally drop as we age.

    Working with mice and cultured cells, they found that, indeed, enzymes that are needed to manufacture polyamines undergo cycles that are tied to both feeding and circadian rhythms of day and night. In mice engineered to lack a functional circadian clock, these fluctuations did not occur.

    As the researchers continued to investigate, they discovered a sort of feedback loop, so that polyamine production is not only regulated by circadian clocks, these substances also regulate the ticking of those clocks, in turn. In cell cultures, adding high levels of polyamines more or less obliterated the circadian rhythm while maintaining low levels slowed the clock by around two hours. “The polyamines are actually an embedded part of the circadian clockwork,” says Asher.

    The scientists then asked how this plays out in younger and older mice, with naturally higher or lower polyamine levels. It is known that the circadian clocks of elderly mice and run slower; concomitantly, their polyamine levels decline. The team found they could slow down the clocks in the young mice by administering a drug to inhibit polyamine synthesis. In contrast, adding a polyamine to the older mice’s drinking water made their clocks run faster than others of their age group and actually restored their function, similar to that of the young mice.

    Asher and his team intend to continue investigating the function of polyamines in circadian systems. “This discovery demonstrates the tight intertwining between circadian clocks and metabolism,” says Zwighaft. “Our findings today rely on experiments with mice, but we think they might hold true in humans. If so, they will have broad clinical implications,” Asher says. “The ability to repair the clock simply, through nutritional intervention with polyamine supplementation, is exciting and obviously of great clinical potential.”

    See the full article here .

    Please help promote STEM in your local schools.

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 10:33 am on October 11, 2015 Permalink | Reply
    Tags: , , , Weizmann Institute of Science   

    From Weizmann: “Getting to the Center” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    14-06-2015
    No Writer Credit

    1
    The nucleus (red) in the cell center is surrounded by the disorganized actin network in the cytoplasm, on which the myosin-v motors move the vesicles around in the “active random motion” No image credit.

    Before an egg – whether mouse or human – can be fertilized, it must get its “internal affairs” in order. That includes moving its nucleus into position in the exact center of the cell. Under a microscope, the nucleus appears to do a little dance, jigging its way from the edge of the cell to the middle. What is really going on?

    “This is a question that physics can answer,” says Prof. Nir Gov of the Weizmann Institute’s Chemical Physics Department. “We examine the physics of the biological molecules in the cell to see whether the means of motion that are proposed are mechanically possible.” Gov, a theoretical physicist, worked with physicists and biologists led by Prof. Marie-Helen Verlhac at the College de France in Paris, observing what happens to the nuclei in mouse egg cells.

    The nucleus dance, they found, is the result of bumping: Tiny motorized sacs called vesicles continually collide with the nucleus. These vesicles run on tracks – the long, thin actin filaments that provide the cell with support – and they are transported by molecular motors made of a kind of myosin – a relative of the myosin that makes our muscles contract. (“The vesicles with their myosin motors underneath look like little people running on a track,” says Gov.)

    But the actin fibers form a disorganized network in the cell’s cytoplasm, and the movement of the vesicles is random as well. How does this random motion turn into the directed movement of the nucleus? This is where the physics came in. The mechanism that indeed explains the movement turned out to be subtle but effective.

    2
    Prof. Nir Gov

    The researchers found that the motors carrying the vesicles move more vigorously at the cell’s outer edges and more slowly in its center. Since there is about the same number of vesicles everywhere, this means that the bumping is more intense from one side. As the nucleus moves in toward the center, however, the force of the vesicles striking it gradually drops until it reaches the point at which the pressure is equally low all around. The physical model for this motion also reveals that the myosin motors stir up the cytoplasm, making it more fluid so that the nucleus can slide through it more easily.

    Further investigations showed that, unlike the active motion of the vesicles, “random thermal motion” – the heat-induced movement that makes molecules “jumpy” – cannot give rise to this type of movement, and would not be able to direct the nucleus to the center of the cell.

    How does the differential velocity of the tiny motors arise in the cell? This open question is under further study. “This is the first time that we have seen such ‘active random motion’ perform work in biological systems,” says Gov. “Since almost all cells contain actin transport systems, we think it could play a role in other types of intracellular movements. As well as solving a biological puzzle, we have learned something new about basic physics by researching movement in cells,” he adds.

    See the full article here .

    Please help promote STEM in your local schools.

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
  • richardmitnick 8:41 am on September 7, 2015 Permalink | Reply
    Tags: , , Weizmann Institute of Science   

    From Weizmann: “Stick and Slip” 

    Weizmann Institute of Science logo

    Weizmann Institute of Science

    Undated
    No Writer Credit

    What do the sounds of a creaky old hinge and a cello have in common? Both rely on the same kind of friction: two surfaces that alternately stick and slide against one another. This physical phenomenon is called stick-slip and, in the case of the creaky hinge, it is often mitigated by the application of a lubricant between the surfaces. It has long been accepted that such a thin layer of lubrication between sliding surfaces alternates along with the cycles of sticking and slipping; it starts as a solid, turns to liquid in the slipping phase and then back to a solid when the surfaces stick once again. But a recent paper in the Proceedings of the National Academy of Sciences (PNAS) suggests this model is incorrect. The findings arose out of research by the group of Prof. Jacob Klein of the Weizmann Institute’s Materials and Interfaces Department, with the collaboration of Prof. Arie Yeredor of Tel Aviv University.

    1
    The sound of a violin arises from a type of friction known as “stick-slip”

    The group – including research student Irit Rosenhek-Goldian and associate staff scientist Dr. Nir Kampf, both members of Klein’s lab – tested this assumption in an ideal system: two perfectly smooth surfaces separated by a thin layer of lubricating material. The material in question contains molecules organized in layers, totaling around four to five nanometers in thickness. The idea was that as the surfaces stuck and then slipped, the lubricant molecules would also stick – as a solid – and then liquefy and slip over one another fluidly.

    The shift from solid to liquid should entail another change: “When a material is solid, it is generally denser than its liquid form,” says Klein. “Thus, when the lubricating material turns liquid, it should physically expand by around ten percent; that is, the thin lubricant layer should expand by around 0.5 nanometers.” But where there should have been a bit more space between the surfaces in the slip stage, there was none. The measurements, which were accurate down to 0.1 nanometers, revealed no change at all in the volume of the lubricant as it went from stick to slip and back again. The conclusion: The lubricant does not change from solid to liquid after all.

    Since friction and wear account for billions of dollars of loss annually, a better understanding of the basic science underlying lubrication may lead to significant improvements in both biomedical and industrial applications.

    Prof. Jacob Klein’s research is supported by the European Research Council. Prof. Klein is the incumbent of the Hermann Mark Professorial Chair of Polymer Physics.

    See the full article here .

    Please help promote STEM in your local schools.

    STEM Icon

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    Weizmann Institute Campus

    The Weizmann Institute of Science is one of the world’s leading multidisciplinary research institutions. Hundreds of scientists, laboratory technicians and research students working on its lushly landscaped campus embark daily on fascinating journeys into the unknown, seeking to improve our understanding of nature and our place within it.

    Guiding these scientists is the spirit of inquiry so characteristic of the human race. It is this spirit that propelled humans upward along the evolutionary ladder, helping them reach their utmost heights. It prompted humankind to pursue agriculture, learn to build lodgings, invent writing, harness electricity to power emerging technologies, observe distant galaxies, design drugs to combat various diseases, develop new materials and decipher the genetic code embedded in all the plants and animals on Earth.

    The quest to maintain this increasing momentum compels Weizmann Institute scientists to seek out places that have not yet been reached by the human mind. What awaits us in these places? No one has the answer to this question. But one thing is certain – the journey fired by curiosity will lead onward to a better future.

     
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