Weizmann Institute

An artificial odour test

(image from wis-wander.weizmann.ac.il)

Say someone claims to have developed a system to “capture” any odour in the form of a digital code – one that could be transmitted online or uploaded to the internet and faithfully reproduced at the receiving end. How could we be sure that the system is valid? In other words, how can we know that, for any possible odour someone has captured digitally and transmitted, the smell we receive is indeed a recognizable, fair rendition of the original?

Prof. David Harel of the Weizmann Institute of Science’s computer science and applied mathematics department explains that, as opposed to video and audio, an odour reproduction system is still far from viable, although some of the components already exist.

“We still don’t understand the process by which the numerous combinations of odourants in our environment are identified and sensed as a particular smell in our brains after they enter our noses, attach to the several hundred kinds of odour receptors there and are transferred to the brain as signals,” he said. But he and his colleagues had, already 15 years ago, laid out the basic principles of such a digital smell system.

This system would need a “sniffer” – a sort of artificial nose – to take “snapshots” of the odourous substances in the air. It would also need a “whiffer” that, something like a colour printer, would be able to mix a fixed set of around 50 chemical odourants in precisely given proportions – something in the way a printer mixes a small number of inks – and release measured amounts of the resulting odour into the air accurately, in a controlled manner.

photo - Prof. David Harel of the Weizmann Institute of Science — Prof. David Harel of the Weizmann Institute of Science. *(photo from wis-wander.weizmann.ac.il)*

Harel believes that such systems will eventually exist, pointing out that research is continually improving our understanding of how smell is “encoded” and how we perceive it. Although reasonably good sniffers and whiffers exist, the tantalizing scientific challenge is to work out the algorithm for connecting the sniffer’s reading into the whiffer’s emission; that is, a method is needed for translating any given odour into precise instructions for the whiffer to follow. The output mixtures would have to be experienced by humans in the way that photos are today – as reproductions that our sense recognizes as faithfully capturing the original.

Despite the fact that this challenge appears to be extremely difficult, Harel recently devised a test that could be used to assess the validity of such a system, if and when one is proposed. One of his inspirations was the Turing test proposed by the British father of computer science, Alan Turing, to test claims of human-like intelligence in a machine. A tester sits in one room and holds conversations with entities in two other rooms – one a human and the other the candidate computer. Through questions, chitchat and serious discourse, the tester tries to identify which is which; if repeated tests cannot distinguish the computer from the human, it is said to possess artificial intelligence. “The problem with using such a test for artificial olfaction,” said Harel, “is that such blind comparisons are detached from the element of human recognizability; and there is no adequate language to describe smells in general, meaning verbal discussions would not work either.”

Harel devised a “lineup” test, whose key feature is the immersion of odours with their natural audio-visual references, thus eliminating the need for verbal description. A team of neutral testers is given several short video clips – for example, of a bakery, a zoo, a dusty attic, a flowering meadow, etc. – and is asked to match an odour emitted by the sniffer with its correct clip. The clips are prepared by a team of challengers, whose role is to try to disprove the claim that the proposed system is valid.

To make sure that the test is fair – for example, the subjects won’t be required to identify the odour of a damp cave hidden from view in the clip of a meadow scene – the group is divided into two. One half is exposed to the actual odours collected and preserved at the video sites, and the other to the artificial, chemically reproduced odour created by the sniffer-whiffer system. That way, the second team of participants – those smelling the whiffer output – are required only to correctly match the odour to its clip when the first team – those exposed to the real odour – succeeds. As in the Turing test, the artificial is pitted against the natural in a blinded experiment, but here the test uses odour immersion for recognizability, and the test is asymmetric, requiring from the artificial no more than is required from the real thing in order to be declared successful.

For more on the research being conducted at the Weizmann Institute, visit wis-wander.weizmann.ac.il.

How trees adapt to conditions

The Weizmann Tree Lab, left to right: Dr. Tamir Klein, Ido Rog, Yael Wagner, Omri Lapidot and Shacham Magidish. (screenshot from wis-wander.weizmann.ac.il)

While studying trees during his postdoctoral fellowship, Dr. Tamir Klein made such a startling discovery that his research supervisor at the University of Basel at first declared that it must have been a mistake. In the forest, trees are known to compete for resources such as light and nutrients, but Klein found that the same trees also engage in sharing: he showed that carbon molecules taken up by the canopies of mature spruce trees were passed through the soil in large quantities to neighbouring beech, larch and pine. As he reported in Science in 2016, the carbon was being transferred via “underground highways” formed by overlapping networks of root fungi.

“Neighbouring trees interact with one another in complex ways,” said Klein. “Of course, there is a great deal of competition among them, but they also form communities, sorts of ‘guilds,’ within which individual trees share valuable resources. In fact, trees belonging to a ‘guild’ usually do much better than those that don’t.”

In his new lab in the Weizmann Institute’s plant and environmental sciences department, Klein follows up on these findings to investigate tree ecophysiology: how the tree functions in its ecosystem.

“Studies on ‘underground’ tree collaboration may reveal which tree species get along well, and this may help determine which trees should be planted next to one another,” he said. “Our studies have additional relevance to forestry and agriculture because we elaborate on the mechanisms of growth and drought resistance of different tree species.”

Only five percent of Israel’s land is covered by forest, but the country nonetheless offers unique advantages for forest research: its hot, dry climate provides an opportunity for investigating how trees adapt to drought and stress. Many trees common to Israel are already resistant to drought; understanding the mechanisms that allow them to live with little rain may help develop varieties of lemons, almonds, olives and other tree crops that can grow in even drier areas.

image - A micro-computer tomography scan of a Jerusalem pine branch, performed after a dry spell, reveals large amounts of air (blue) filling the water channels — A micro-computer tomography scan of a Jerusalem pine branch, performed after a dry spell, reveals large amounts of air (blue) filling the water channels. *(image from wis-wander.weizmann.ac.il)*

Projects in Klein’s lab aim to clarify how trees manage their water and carbon budgets – both separately and as a forest community. In one study, the team focuses on emboli: tiny air bubbles that form inside the tree’s water channels during drought. When drought persists, the emboli can kill a tree, much like blood vessel clots that can cause a fatal heart attack in a human being. After injecting fluids into tree branches at different pressures, Klein and his students analyze the emboli in the minutest detail, using micro-computed tomography.

In Weizmann’s greenhouses, Klein’s team members experiment with seedlings of pine, cypress, carob and other trees commonly found in Israel. The researchers make use of advanced technologies, including nuclear magnetic resonance imaging, to study hydraulic conductivity in trees and a special lamp-equipped belowground camera to study the growth of tree roots in the soil.

When conducting field studies on their research plot near Beit Shemesh, Klein and his students hug trees – not to have a spiritual experience, but to follow a tree’s growth by encircling the trunk with a measuring tape. In parallel, they apply laser isotope analysis and analytical chemistry techniques to trace carbon metabolism in individual trees, and they investigate carbon transfer among trees via different types of fungal “highways.” The scientists also employ thermal imaging, which enables remote temperature measurements, to study the rate of evaporation in the foliage.

These studies will help predict how future climate changes, including global warming and the rise in greenhouse gases, may affect forests. In one set of experiments, for example, Klein will double the concentration of CO₂ to mimic the atmospheric conditions that may emerge on earth as a result of pollution. Klein hasn’t owned a car in 10 years, so as not to contribute to CO₂ emissions, but he warns against jumping to conclusions when it comes to the impact of increased CO₂ on tree biology. “Higher CO₂ concentrations don’t help trees grow faster – contrary to the hopes of industrialists – but, surprisingly, recent research suggests they might render the trees more resistant to drought-induced stress. This doesn’t mean it’s OK to carry on with CO₂ pollution, but it does mean that we need to deepen our understanding of its effects on trees in general and on agricultural tree crops in particular.”

Klein is the incumbent of the Edith and Nathan Goldenberg Career Development Chair. His research is supported by Nella and Leon Y. Benoziyo; and Norman Reiser. More on Weizmann Institute research can be found at wis-wander.weizmann.ac.il.

Triple treatment for cancer

Lung cancer cells (green) cultured together with normal lung cells (red). The triple-antibody combination EGFR, HER2 and HER3 strongly impairs the survival of tumor cells while sparing normal cells. (Modified confocal microscopy image by Maicol Mancini, lab of Prof. Yosef Yarden, via wis-wander.weizmann.ac.il)

Lung cancer is the leading cause of cancer death worldwide, responsible for some 1.59 million deaths a year. That figure is due, in part, to the fact that the cancer often returns after what, at first, seems to be successful treatment. And the recurring cancer is often resistant to the chemotherapy and other drugs that originally drove it into remission. According to new research by the Weizmann Institute’s Prof. Yosef Yarden, a new strategy involving a three-pronged approach might keep an aggressive form of lung cancer from returning.

photo - Prof. Yosef Yarden — Prof. Yosef Yarden *(photo from National Cancer Institute via commons.wikimedia.org)*

The research arose out of some puzzling results of clinical trials, said Yarden. One class of relatively common lung cancers, which carry a particular mutation in a receptor on the cell membrane, called EGFR, can be treated with a sort of “wonder drug.” This drug keeps a growth signal from getting into the cell, thus preventing the deadly progression and spread of the cancer. But within a year, those with this mutation invariably experience new cancer growth, usually as a result of a second EGFR mutation. To prevent this from happening, researchers had tried to administer another drug, an antibody that is today used to treat colorectal cancer. This drug also obstructs the passing of the growth signal by stopping EGFR. Even though the antibody drug should have been able to effectively block the EGFRs – the growth receptors – including those generated by the second mutation, clinical trials of this drug for lung cancer did not produce results. “This finding ran counter to everything we knew about the way tumors develop resistance,” said Yarden.

How do the cancer cells manage to circumvent the blockade put up by an anti-EGFR antibody? In the new study, which appeared earlier this month in Science Signaling, Yarden and his student, Maicol Mancini, discovered what happens to cancer cells when they are exposed to the receptor-blocking antibody.

“The blocked receptor has ‘siblings,’ other receptors that can step up to do the job,” explained Yarden. Indeed, the team found that when the main receptor (EGFR) continued to be blocked, one of the cell’s communication networks was rerouted, causing the siblings to appear on the cell membrane instead of the original receptor. The finely tuned antibody did not block these, and thus the cancer cells were once again “in business.” The researchers uncovered the chain of protein communication in the new network that ultimately leads to appearance of the sibling growth receptors. This new network may overcompensate for the lack of the original receptor, making it even worse than the original. In addition, the team found that the rewired network sometimes included the participation of another molecule, known as receptor tyrosine kinase MET, which specifically binds to one of the siblings. This signaling molecule is often found in metastatic cancers.

Once the researchers discovered how the blockade was breached, they set out to erect a better line of defence. Yarden and his team created new monoclonal antibodies that could target the two main growth receptor siblings, named HER2 (the target of the breast cancer drug Herceptin) and HER3. The idea was to give all three antibodies together – the two new ones and the original anti-EGFR antibody – to preempt resistance to the treatment. Indeed, in isolated cancer cells, applying the triple treatment prevented them from completing the rewiring necessary for continuing to receive growth signals.

Next, the team tried the three-pronged approach on mouse models of lung cancer that had the secondary, resistance mutation. In these mice, the tumor growth was almost completely arrested. More importantly, further research showed that this treatment reined in the growth of the tumor while leaving healthy cells alone.

Although much more research is required before the triple-treatment approach makes it to the clinic, Yarden is hopeful that it will change not only the treatment protocol for lung cancer, but the understanding of the mechanisms of drug resistance. “Treatment by blocking a single target can cause a feedback loop that ultimately leads to a resurgence of the cancer,” he said. “If we can predict how the cancer cell will react when we block the growth signals it needs to continue proliferating, we can take preemptive steps to prevent this from happening.”

Also participating in this research were Drs. Nadège Gaborit, Moshit Lindzen and Tomer Meir Salame of the biological services department, and Ali Abdul-Hai, also of Kaplan Medical Centre; and research students Massimiliano Dall’Ora and Michal Sevilla-Sharon; together with Prof. Julian Downward of the London Research Institute.

Yarden is the recipient of the 2015 Leopold Griffuel Prize for fundamental research, awarded by the major French association for fighting cancer, called ARC Foundation for Cancer Research. He is the incumbent of the Harold and Zelda Goldenberg Professorial Chair in Molecular Cell Biology.

Weizmann Institute news releases are posted at wis-wander.weizmann.ac.il, and are also available at eurekalert.org.

Hospital hears about ASA

Dr. Ayelet Erez (photo from weizmann.ac.il)

Dr. Ayelet Erez, a visiting clinician scientist from the Weizmann Institute in Rehovot, Israel, was invited to speak at B.C. Children’s Hospital earlier this month.

The group was comprised of clinicians, researchers and clinical lab scientists. The event was organized by Dr. Hilary Vallance, a Weizmann Vancouver chapter member, who is director of the B.C. Newborn Screening Program and the Biochemical Genetics Lab within the department of pathology at the hospital.

Erez gave a talk on argininosuccinic aciduria (ASA), a rare inherited disorder caused by a lack of the functional gene necessary to make an enzyme called argininosuccinate lyase. Her talk led to a discussion with members of the hospital’s metabolic division in attendance regarding various aspects of her research and how her findings could potentially improve the practice of treating patients with argininosuccinate lyase deficiency here in British Columbia.

For more information on Erez or Weizmann Canada events in Vancouver, contact Jan Goldenberg, [email protected], or call 1-855-337-9611.

Belzberg honored

Samuel Belzberg is being honored as a “leading man” on Nov. 16 in Toronto. (photo from Weizmann Institute)

When Weizmann Canada’s Leading Men Gala is held Nov. 16 in Toronto, Samuel Belzberg will be one of the 10 honorees and the only one from Western Canada. Vancouver-based Belzberg will be in the audience of 500 that night and he and other honorees will address the audience in a video presentation, revealing their thoughts, comments and inspiration.

“We’ve never had an event on this scale before,” said Susan Stern, national executive director for Weizmann Canada. “But it’s our 50th anniversary and we wanted to do something really special.” The national event has an ambitious financial goal of raising $5 million to support the Weizmann Institute of Science in Rehovot, Israel. Speakers include actor William Shatner and Prof. Oded Aharonson, who will deliver a multimedia presentation about his research on extraterrestrial oceans.

Stern said she expected the dinner to sell out, adding that tables start at $50,000 and that there are various levels of sponsorship.

In selecting the honorees for the gala, Weizmann Canada’s goal was to find individuals who had distinguished themselves as leaders in their field, who understood the value of giving back and who had done something special in areas of research that were close to their hearts. Belzberg was an easy choice.

Founder and chairman of Gibralt Capital Corp. and Second City Real Estate, his two companies manage and own more than $500 million of real estate and capital investments. Back in 2001, he created Action Canada, which, in partnership with the federal government, endows 20 fellowships each year to Canadians who want to make a difference in the world.

It’s easy to look at the dollar figures his companies represent and assume that life has been just rosy for Belzberg, a father of four who boasts 16 grandchildren and eight great-grandchildren. But look a little deeper and it becomes clear that every family has its own unique battles. In Belzberg’s case it was the illness of one of his daughters, Cheri, who was diagnosed with dystonia, a neurological disorder that impacted her mobility and speech. Back in the 1970s, when doctors were trying to diagnose her condition, finding the right diagnosis took four to five years. “Nobody knew the first thing about it in those days,” he said.

Belzberg would change that, establishing the Dystonia Foundation with neurologist Stanley Fahn in 1976. The foundation has made significant contributions to clinical and diagnostic treatments though, sadly, none of them helped Cheri. Still, Belzberg is encouraged by the progress in research and the fact that it has given thousands of people cures for the disorder, as well as counseling and support.

“We have now learned that there are many different types of dystonia and we’ve been at the forefront of learning about them and finding either cures or short-term help,” he said. “For example, there’s a kind of dystonia that’s like writer’s cramp, or where a musician all of a sudden couldn’t play the piano.”

Belzberg has established many other initiatives, too. “He’s done so much for the community, locally, nationally and internationally – it’s unbelievable,” Stern said. In 1977, he created the Simon Wiesenthal Centre and the Museum of Tolerance in Los Angeles. The mission of the centre is to confront antisemitism, promote human rights and ensure that the Holocaust is never forgotten.

Belzberg, however, credits his success to picking the right partners for his projects. “It’s relatively easy to donate money, but it’s not so easy to take your time and actually work at a project,” he admitted. “I’ve been very lucky in that I’ve picked good partners. They carry the ball and I help the best way I can.”

He added that his involvement with Weizmann Canada over the years was prompted by a belief that the Weizmann Institute “is among the greatest institutes in Israel. The scientists at Weizmann have accomplished so much, and it’s a great honor to be playing a small part in moving the research forward.”

Lauren Kramer, an award-winning writer and editor, lives in Richmond, B.C. To read her work online, visit laurenkramer.net.

Reading gut bacteria

(photo from wis-wander.weizmann.ac.il)

Our species’ waking and sleeping cycles – shaped in millions of years of evolution – have been turned upside down within a single century with the advent of electric lighting and airplanes. As a result, millions of people regularly disrupt their biological clocks – for example, shift workers and frequent flyers – and these have been known to be at high risk for such common metabolic diseases as obesity, diabetes and heart disease. A new study published in Cell, led by Weizmann Institute scientists, reveals for the first time that our biological clocks work in tandem with the populations of bacteria residing in our intestines, and that these micro-organisms vary their activities over the course of the day. The findings show that mice and humans with disrupted daily wake-sleep patterns exhibit changes in the composition and function of their gut bacteria, thereby increasing their risk for obesity and glucose intolerance.

A consensus has been growing in recent years that the populations of microbes living in and on our bodies function as an extra “organ” that has wide-ranging impacts on our health. Christoph Thaiss, a research student in the lab of Dr. Eran Elinav of the Weizmann Institute’s immunology department, led this research into the daily cycles of gut bacteria. Working together with David Zeevi in the lab of Prof. Eran Segal of the computer science and applied mathematics department, and Maayan Levy of Elinav’s lab, he found a regular day-night cycle in both the composition and the function of certain populations of gut bacteria in mice. Despite living in the total darkness of the digestive system, the gut microbes were able to time their activity to the mouse’s feeding cycles, coordinating daily microbial activities to those of their host.

Does this finding have any medical significance? To further investigate, the researchers looked at “jet-lagged” mice, whose day-night rhythms were altered by exposing them to light and dark at different intervals. The jet-lagged mice stopped eating at regular times, and this interrupted the cyclic rhythms of their internal bacteria, leading to weight gain and high blood sugar levels. To verify these results, the scientists transferred bacteria from the jet-lagged mice into sterile mice; those receiving the “jet-lagged microbes” also gained weight and developed high blood sugar levels.

The research group then turned to human gut bacteria, identifying a similar daily shift in their microbial populations and function. To conduct a jet-lag experiment in humans, the researchers collected bacterial samples from two people flying from the United States to Israel – once before the flight, once a day after landing when jet lag was at its peak, and once two weeks later when the jet lag had worn off. The researchers then implanted these bacteria into sterile mice. Mice receiving the jet-lagged humans’ bacteria exhibited significant weight gain and high blood sugar levels, while mice getting bacteria from either before or after the jet lag had worn off did not. These results suggest that the long-term disruption of the biological clock leads to a disturbance in their bacteria’s function that may, in turn, increase the risk for such common conditions as obesity and imbalances in blood sugar levels.

Segal: “Our gut bacteria’s ability to coordinate their functions with our biological clock demonstrates, once again, the ties that bind us to our bacterial population and the fact that disturbances in these ties can have consequences for our health.”

Elinav: “Our inner microbial rhythm represents a new therapeutic target that may be exploited in future studies to normalize the microbiota in people whose life style involves frequent alterations in sleep patterns, hopefully to reduce or even prevent their risk of developing obesity and its complications.”

Also participating in this research were Gili Zilberman-Schapira, Jotham Suez, Anouk Tengeler, Lior Abramson, Meirav Katz and Dr. Hagit Shapiro in Elinav’s lab; Tal Korem in Segal’s lab; Prof. Alon Harmelin, Dr. Yael Kuperman and Dr. Inbal Biton of the veterinary resources department, Dr. Shlomit Gilad of the Nancy and Stephen Grand Israel National Centre for Personalized Medicine; and Prof. Zamir Halpern and Dr. Niv Zmora of the Sourasky Medical Centre and Tel Aviv University.

Weizmann Institute news releases are posted at wis-wander.weizmann.ac.il and eurekalert.org.

Untangling the womb maze

Fluid-filled structures in the placenta. (photo from wis-wander.weizmann.ac.il)

The fetus in the womb totally depends on the blood bond with the mother. Spotting irregularities in the flow across the placenta could therefore be crucial for detecting fetal distress,

but currently no reliable method is available for monitoring the flow or detecting other signs of the distress in its early stages.

Magnetic resonance imaging, or MRI, can be safely performed during pregnancy, but currently available MRI methods are not suitable. Problems include the motion of the fetus or mothers’ breath, the varied structure of placental tissue and the tangled maze formed by maternal and fetal blood vessels.

In a new study in mice conducted with advanced MRI methods, Weizmann Institute scientists have now revealed in unprecedented detail the dynamics of the flow of fluids within the placenta. This feat was all the more impressive, as a mouse placenta is around the size of a dime. As reported recently in the Proceedings of the National Academy of Sciences, they managed to identify three different types of fluid-filled structures: maternal blood vessels, which account for two-thirds of blood flow in the placenta; fetal vessels, which account for about one-quarter of the flow; and embryo-derived cells infiltrating the mother’s vasculature, which account for the rest of the flow and in which the exchange of fluids between mother and fetus takes place. The researchers also found that in maternal vessels, blood flows by diffusion, whereas in fetal vessels, the flow, stimulated by the pumping of the growing fetus’ heart, is much faster. In the cells that have infiltrated the mother’s vasculature, the dynamics of the flow follows an intermediate pattern, driven by both diffusion and pumping.

Two sophisticated MRI methods were combined to enable the study: one geared toward monitoring diffusion and another directed at identifying structures with the help of a contrast material. They could be applied successfully in large part thanks to an innovative scanning approach, spatiotemporal encoding (SPEN), a Weizmann Institute technique. Because SPEN is ultra-fast and makes it possible to separately encode signals from such different materials as air or fat, it allowed the researchers to overcome disturbances created by movement and the variability of placental tissue. If developed further for safe and reliable use in humans, this combined approach holds great promise as a noninvasive means of detecting fetal distress caused by disruptions in the placental flow. It can be particularly valuable when fast decisions about inducing labor need to be made, for example, in such complications of pregnancy as preeclampsia.

The study was a joint effort of two laboratories: one headed by Prof. Michal Neeman of the biological regulation department and the other by Prof. Lucio Frydman of the chemical physics department. The research was performed by two graduate students, Reut Avni from Neeman’s lab and Eddy Solomon from Frydman’s lab, together with Ron Hadas and Dr. Tal Raz of the biological regulation department, and Dr. Peter Bendel of chemical research support, in collaboration with Prof. Joel Richard Garbow from Washington University in St. Louis.

For more Weizmann news, visit wis-wander.weizmann.ac.il.

How mammals respond to novelty

Measuring the response to novelty: A mouse repeatedly touches the object and pulls away (nose and whisker contacts are color-coded; d is the distance of the snout from the object). (photo from wis-wander.weizmann.ac.il)

Put a young child in a new playground and she may take awhile to start playing – approaching the slide and then running back to Mom before finally stepping on. A new model suggests that it is not fear that makes her run back and forth, but simply the fact that her brain is telling her to stop and take in the new information – the height of the slide or how slippery it appears – before going any further.

Drs. Goren Gordon and Ehud Fonio, and Prof. Ehud Ahissar, believe that this is a basic pattern in mammals that governs how we learn. The mathematical model they developed and tested in experiments suggests that our innate curiosity is tempered by mechanisms in our brains that curb our ability to absorb novelty.

In Ahissar’s lab in the institute’s neurobiology department, researchers investigate how animals sense their surroundings. Previous research in which Fonio participated showed that, in a new situation, a mouse would approach an unfamiliar space, retreat to familiar surroundings, and then approach again. When Gordon, Fonio and Ahissar examined how mice used their whiskers to feel out a novel object, a similar pattern ensued: the whisker would touch the object, pull back and then touch it again. Gradually, as the mouse became familiar with one part of its surroundings, it would begin to explore further, moving away from the known part. The pattern was so consistent, the researchers thought they could create a model to explain how a mouse – or another mammal – explores new surroundings.

The researchers based their model on the premise that novelty can be measured and that the amount of novelty could be a primary factor in shaping the way that a mouse – or its whisker – will move through an environment. This model successfully reproduced the results of the previous study, in which the movement of the mouse gradually became more complex through the addition of measurable degrees of freedom. For example, it began with movement along a wall, as opposed to traveling across the open space. Using data from the previous experiments and others for which such data were available, they were able to construct a model that required very few additional assumptions.

The model suggested that novelty, per se, was not the deciding factor, but rather how much the novelty varied within a given situation. Approaching and retreating appear to be a way to keep the amount of new information within a constant range. Like the wavering child in the playground, the mice would absorb a certain amount of new sensory input – the curve of a new wall, for example – retreat, and approach again once the novel information was already starting to become familiar.

To test the model, the researchers designed an experimental setup in which a family of mice was born and raised in a den, and then a gate was opened from the den to a new area in which the pups could freely explore and return to their familiar den. The researchers found that the model was able to predict how the mice would explore their new surroundings. It held true whether it was applied to locomotion or to the motion of whiskers in feeling out new objects. The initial movements explored the most novel features of the new environment. After those were learned, just as the model predicted, the animals moved further afield, exploring the still-unknown parts of their surroundings.

“The mice were not given rewards for their behavior – for them, as for humans, satisfying curiosity is its own reward,” said Gordon.

“This behavioral pattern enables the mice to control the level of sensory stimulus to their brains by regulating the amount of novelty they are exposed to,” added Fonio.

These limits to novelty and exploration may, of course, have another evolutionary advantage: while the urge to explore is necessary for animals that must seek out food, stopping to check out the surroundings a bit at a time could be a prudent survival strategy. In other words, curiosity may have killed the cat, but a whisker pulled back in time might save the mouse.

Does this model apply to humans? Gordon points out that when we learn a new subject, we often need time to think things over before going on to the next topic. Further research might reveal whether young children – babies just learning to crawl, for example – explore their new surroundings in the same way. Even an adult entering a new situation might undergo a similar process.

In the future, a mathematical model of learning might prove useful for teachers and students, as well as for research into neurological issues involving the ability to absorb new information. This model also might someday be used in the field of robotics: robots that learn on their own, like mice, to explore a new setting might be able to function in situations that are too dangerous for humans, such as the aftermath of an earthquake or a nuclear power plant accident, for example.

For more Weizmann Institute news releases, visit wis-wander.weizmann.ac.il.

Peering into universe’s past

A small black hole gains mass. Dense cold gas (green) flows toward the centre of a stellar cluster (red cross in blue circle) with stars (yellow); the erratic path of the black hole through the gas (black line) is randomized by the surrounding stars. (photo from wis-wander.weizmann.ac.il)

At the ends of the universe, there are black holes with masses equaling billions of our sun. These giant bodies – quasars – feed on interstellar gas, swallowing large quantities of it non-stop. Thus, they reveal their existence: the light that is emitted by the gas as it is sucked in and crushed by the black hole’s gravity travels for eons across the universe until it reaches our telescopes. Looking at the edges of the universe is, therefore, looking into the past. These far-off, ancient quasars appear to us in their “baby photos” taken less than a billion years after the Big Bang: monstrous infants in a young universe.

Normally, a black hole forms when a massive star, weighing tens of solar masses, explodes after its nuclear fuel is spent. Without the nuclear furnace at its core pushing against gravity, the star collapses. Much of the material is flung outwards in a great supernova blast, while the rest falls inward, forming a black hole of only about 10 solar masses.

Since these ancient quasars were first discovered, scientists have wondered what process could lead a small black hole to gorge and fatten to such an extent, so soon after the Big Bang.

In fact, several processes tend to limit how fast a black hole can grow. For example, the gas normally does not fall directly into the black hole, but gets sidetracked into a slowly spiraling flow, trickling in drop by drop. When the gas is finally swallowed by the black hole, the light it emits pushes out against the gas. That light counterbalances gravity, and it slows the flow that feeds the black hole.

So how, indeed, did these ancient quasars grow? Prof. Tal Alexander, head of the particle physics and astrophysics department at the Weizmann Institute of Science, proposes a solution in a paper written together with Prof. Priyamvada Natarajan of Yale University, which appeared in a recent issue of Science.

Their model begins with the formation of a small black hole in the very early universe. At that time, cosmologists believe, gas streams were cold, dense and contained much larger amounts of material than the thin gas streams we see in today’s cosmos. The hungry, newborn black hole moved around, changing direction all the time, as it was knocked about by other baby stars in its vicinity. By quickly zigzagging, the black hole continually swept up more and more of the gas into its orbit, pulling the gas directly into it so fast, the gas could not settle into a slow, spiraling motion. The bigger the black hole got, the faster it ate; this growth rate, explained Alexander, rises faster than exponentially. After around 10 million years – a blink of an eye in cosmic time – the black hole would have filled out to around 10,000 solar masses. From then, the colossal growth rate would have slowed to a somewhat more leisurely pace, but the black hole’s future path would already be set – leading it to eventually weigh in at a billion solar masses or more.

Alexander’s research is supported by the European Research Council. Visit wis-wander.weizmann.ac.il for more Weizmann news.

DNA’s not only factor

Epigenetics: environmental effects influence how genes are turned on or off. (photo by Yuval Robichek via wis-wander.weizmann.ac.il)

Blood stem cells have the potential to turn into any type of blood cell, whether it be the oxygen-carrying red blood cells or the many types of white blood cells of the immune system that help fight infection. How exactly is the fate of these stem cells regulated? Preliminary findings from research conducted by scientists from the Weizmann Institute and the Hebrew University are starting to reshape the conventional understanding of the way blood stem-cell fate decisions are controlled, thanks to a new technique for epigenetic analysis they have developed.

Understanding epigenetic mechanisms (environmental influences other than genetics) of cell fate could lead to the deciphering of the molecular mechanisms of many diseases, including immunological disorders, anemia, leukemia, and many more. It also lends strong support to findings that environmental factors and lifestyle play a more prominent role in shaping our destiny.

The process of differentiation – in which a stem cell becomes a specialized mature blood cell – is controlled by a cascade of events in which specific genes are turned “on” and “off” in a highly regulated and accurate order. The instructions for this process are contained within the DNA itself in short, regulatory sequences. These regulatory regions are normally in a “closed” state masked by special proteins called histones to ensure against unwarranted activation. Therefore, to access and “activate” the instructions, this DNA mask needs to be “opened” by epigenetic modifications of the histones so it can be read by the necessary machinery.

In a paper published in Science, Dr. Ido Amit and David Lara-Astiaso of the Weizmann Institute’s immunology department, together with Prof. Nir Friedman and Assaf Weiner of Hebrew University, charted for the first time histone dynamics during blood development. From the new technique for epigenetic profiling they developed, in which just a handful of cells – as few as 500 – can be sampled and analyzed accurately, they have identified the exact DNA sequences, as well as the various regulatory proteins, that are involved in regulating the process of blood stem-cell fate.

Their research also yielded unexpected results: as many as 50 percent of these regulatory sequences are established and opened during intermediate stages of cell development. This means that epigenetics is active at stages in which it had been thought that cell destiny was already set. “This changes our whole understanding of the process of blood stem-cell fate decisions,” said Lara-Astiaso, “suggesting that the process is more dynamic and flexible than previously thought.”

Although this research was conducted on mouse blood stem cells, the scientists believe that the mechanism may hold true for other types of cells. “This research creates a lot of excitement in the field, as it sets the groundwork to study these regulatory elements in humans,” said Weiner. Discovering the exact regulatory DNA sequence controlling stem-cell fate, as well as understanding its mechanism, holds promise for the future development of diagnostic tools, personalized medicine, potential therapeutic and nutritional interventions, and perhaps even regenerative medicine, in which committed cells could be reprogrammed to their full stem-cell potential.

For more Weizmann Institute news releases, visit wis-wander.weizmann.ac.il.

– Courtesy of Weizmann Institute