Weizmann Institute

Studying the “love hormone”

Oxytocin, a peptide produced in the brain, may bring hearts together – or it can help induce aggression. (image from Weizmann Institute)

During the pandemic lockdown, as couples have been forced to spend days and weeks in each other’s company, some have found their love renewed while others are on their way to divorce court. Oxytocin, a peptide produced in the brain, is complicated in that way: a neuromodulator, it may bring hearts together or it can help induce aggression. This conclusion arises from research led by Weizmann Institute of Science researchers in which mice living in semi-natural conditions had their oxytocin-producing brain cells manipulated in a precise manner. The findings, which were published in Neuron, could shed new light on efforts to use oxytocin to treat a variety of psychiatric conditions, from social anxiety and autism to schizophrenia.

Much of what we know about the actions of neuromodulators like oxytocin comes from behavioural studies of lab animals in standard lab conditions. These conditions are strictly controlled and artificial, in part so that researchers can limit the number of variables affecting behaviour. But a number of recent studies suggest that the actions of a mouse in a semi-natural environment can teach us much more about natural behaviour, especially when we mean to apply those findings to humans.

Prof. Alon Chen’s lab group in the institute’s neurobiology department have created an experimental setup that enables them to observe mice in something approaching their natural living conditions – an environment enriched with stimuli they can explore – and their activity is monitored day and night with cameras and analyzed computationally. The present study, which has been ongoing for the past eight years, was led by research students Sergey Anpilov and Noa Eren, and staff scientist Dr. Yair Shemesh in Chen’s lab group.

The innovation in this experiment was to incorporate optogenetics – a method that enables researchers to turn specific neurons in the brain on or off using light. To create an optogenetic setup that would enable the team to study mice that were behaving naturally, the group developed a compact, lightweight, wireless device with which the scientists could activate nerve cells by remote control. With the help of optogenetics expert Prof. Ofer Yizhar of the same department, the group introduced a protein previously developed by Yizhar into the oxytocin-producing brain cells in the mice. When light from the wireless device touched those neurons, they became more sensitized to input from the other brain cells in their network.

“Our first goal,” said Anpilov, “was to reach that ‘sweet spot’ of experimental setups in which we track behaviour in a natural environment, without relinquishing the ability to ask pointed scientific questions about brain functions.”

Shemesh added that “the classical experimental setup is not only lacking in stimuli, the measurements tend to span mere minutes, while we had the capacity to track social dynamics in a group over the course of days.”

Delving into the role of oxytocin was sort of a test drive for the experimental system. It had been believed that this hormone mediates pro-social behaviour. But findings have been conflicting, and some have proposed another hypothesis, termed “social salience,” stating that oxytocin might be involved in amplifying the perception of diverse social cues, which could then result in pro-social or antagonistic behaviours, depending on such factors as individual character and the environment.

To test the social salience hypothesis, the team used mice in which they could gently activate the oxytocin-producing cells in the hypothalamus, placing them first in the enriched, semi-natural lab environments. To compare, they repeated the experiment with mice placed in the standard, sterile lab setups.

In the semi-natural environment, the mice at first displayed heightened interest in one another, but this was soon accompanied by a rise in aggressive behaviour. In contrast, increasing oxytocin production in the mice in classical lab conditions resulted in reduced aggression.

“In an all-male, natural social setting, we would expect to see belligerent behaviour as they compete for territory or food,” said Anpilov. “That is, the social conditions are conducive to competition and aggression. In the standard lab setup, a different social situation leads to a different effect for the oxytocin.”

If the “love hormone” is more likely a “social hormone,” what does that mean for its pharmaceutical applications?

“Oxytocin is involved, as previous experiments have shown, in such social behaviours as making eye contact or feelings of closeness,” said Eren, “but our work shows it does not improve sociability across the board. Its effects depend on both context and personality.”

This implies that, if oxytocin is to be used therapeutically, a much more nuanced view is needed in research: “If we want to understand the complexities of behaviour, we need to study behaviour in a complex environment. Only then can we begin to translate our findings to human behaviour,” she said.

Participating in this research were scientists at the Max Planck Institute for Psychiatry in Munich, including research students Asaf Benjamin and Stoyo Karamihalev, staff scientist Dr. Julien Dine and postdoctoral fellow Dr. Oren Forkosh of the Chen lab; Prof. Shlomo Wagner and postdoctoral fellow Dr. Hala Harony-Nicolas of Haifa University; Prof. Inga Neumann and research student Vinicius Oliveira of Regensburg University, Germany; and electrical engineer Avi Dagan.

Cassini’s view of Saturn

Saturn’s main rings, along with its moons, are much brighter than most stars. As a result, much shorter exposure times (10 milliseconds, in this case) are required to produce an image and not saturate the detectors of the imaging cameras on Cassini. A longer exposure would be required to capture the stars as well. (photo from NASA/JPL-Caltech/Space Science Institute)

Grand Finale was the official name of Cassini’s last act: a risky orbit between Saturn’s rings and atmosphere in an attempt to explore the planet up close, right before the craft went up in flames.

Prof. Yohai Kaspi and Dr. Eli Galanti of the Weizmann Institute’s earth and planetary sciences department led one of the studies on Cassini’s final mission, revealing the depth of Saturn’s jet streams – the strongest measured in the solar system, with winds of up to 1,500 kilometres per hour – and found them to reach a depth of around 9,000 kilometres. Teaming up with research partners in Italy and the United States, their study also helped reveal the age of the planet’s rings. The findings of these studies were published this month in Science.

Cassini was one of the more successful planetary missions, orbiting and returning information on Saturn and its moons for the last 20 years. As the mission was approaching its end, it was decided to end its life with a non-circular orbit swinging in very close to the planet, followed by a final plunge into the gaseous mass. Kaspi and Galanti joined the Cassini team following their work as part of NASA’s Juno science team, which had employed a similar orbit to produce the most reliable measurements yet of Jupiter’s atmospheric depth. The Cassini scientists thought it would be possible to do the same for Saturn, and the Weizmann scientists were called in to apply their methodology to the Saturn measurements.

Kaspi described the challenge: “We detect small variations in the gravity field as the craft orbits Saturn, and translate these into the atmospheric wind that produces them. There was no guarantee it would work for Saturn, as the gravity signal on Saturn is more difficult to interpret than what we had on Jupiter. We discovered that not only did it work for both planets, but that same physical processes control the depth of the flows on these two planets.”

To calculate the depth of the winds, the gravity measurements undertaken by Cassini were analyzed with the theoretical model developed by the Weizmann researchers. “We also teamed up with a second group investigating the internal structure of the planet,” said Galanti. “Together, we calculated that the depth of the atmosphere is up to around 9,000 kilometres. That is three times deeper than that of Jupiter. We also found that, just as on Jupiter, a strong internal magnetic field is what limits the depth of this layer of the atmosphere. Our theory worked twice, which provides strong support for its validity.”

In the same study, the researchers analyzed the Grand Finale data from Saturn’s rings, finding they are at most 100 million years old. That is quite recent in the 4.5-billion-year history of the solar system. The planet in the night sky at the time of the first dinosaurs was, apparently, without the rings we know today.

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

– Weizmann Institute

Saturn losing its rings

New NASA research confirms that Saturn is losing its iconic rings at the maximum rate estimated from Voyager 1 and 2 observations made decades ago. The rings are being pulled into Saturn by gravity as a dusty rain of ice particles under the influence of Saturn’s magnetic field.

photo - Saturn’s northern hemisphere in 2016, as that part of the planet nears its northern hemisphere summer solstice in May 2017. Since NASA’s Cassini spacecraft arrived at Saturn in mid-2004, the shifting angle of sunlight as the seasons march forward has illuminated the giant hexagon-shaped jet stream around the north polar region, and the subtle bluish hues seen earlier in the mission have continued to fade — Saturn’s northern hemisphere in 2016, as that part of the planet nears its northern hemisphere summer solstice in May 2017. Since NASA’s Cassini spacecraft arrived at Saturn in mid-2004, the shifting angle of sunlight as the seasons march forward has illuminated the giant hexagon-shaped jet stream around the north polar region, and the subtle bluish hues seen earlier in the mission have continued to fade. *(photo from NASA/JPL-Caltech/Space Science Institute)*

“We estimate that this ‘ring rain’ drains an amount of water products that could fill an Olympic-sized swimming pool from Saturn’s rings in half an hour,” said James O’Donoghue of NASA’s Goddard Space Flight Centre in Greenbelt, Md. “From this alone, the entire ring system will be gone in 300 million years, but add to this the Cassini-spacecraft measured ring-material detected falling into Saturn’s equator, and the rings have less than 100 million years to live. This is relatively short, compared to Saturn’s age of over four billion years.” O’Donoghue is lead author of a study on Saturn’s ring rain appearing in Icarus Dec. 17.

Scientists have long wondered if Saturn was formed with the rings or if the planet acquired them later in life. The new research favours the latter scenario, indicating that they are unlikely to be older than 100 million years, as it would take that long for the C-ring to become what it is today assuming it was once as dense as the B-ring. “We are lucky to be around to see Saturn’s ring system, which appears to be in the middle of its lifetime. However, if rings are temporary, perhaps we just missed out on seeing giant ring systems of Jupiter, Uranus and Neptune, which have only thin ringlets today,” O’Donoghue added.

Various theories have been proposed for the ring’s origin. If the planet got them later in life, the rings could have formed when small, icy moons in orbit around Saturn collided, perhaps because their orbits were perturbed by a gravitational tug from a passing asteroid or comet.

– NASA Goddard Space Flight Centre

Too much food wasted

Millions more could be fed by the same resources if our diets changed. (photo from wis-wander.weizmann.ac.il)

About a third of the food produced for human consumption is estimated to be lost or wasted globally. But the biggest waste, which is not even included in this estimate, may be through dietary choices that result in the squandering of environmental resources. In a study published in the Proceedings of the National Academy of Sciences of the United States of America, researchers at the Weizmann Institute of Science in Rehovot, Israel, and their colleagues have found a novel way to define and quantify this second type of wastage. The scientists have called it “opportunity food loss,” a term inspired by the “opportunity cost” concept in economics, which refers to the cost of choosing a particular alternative over better options.

Opportunity food loss stems from using agricultural land to produce animal-based food instead of nutritionally comparable plant-based alternatives. The researchers report that, in the United States alone, avoiding opportunity food loss – that is, replacing all animal-based items with edible crops for human consumption – would add enough food to feed 350 million additional people, or more than the total U.S. population, with the same land resources.

“Our analysis has shown that favouring a plant-based diet can potentially yield more food than eliminating all the conventionally defined causes of food loss,” said lead author Dr. Alon Shepon, who worked in the lab of Prof. Ron Milo in the plant and environmental sciences department. The Weizmann researchers collaborated with Prof. Gidon Eshel of Bard College and Dr. Elad Noor of ETZ Zürich.

The scientists compared the resources needed to produce five major categories of animal-based food – beef, pork, dairy, poultry and eggs – with the resources required to grow edible crops of similar nutritional value in terms of protein, calories and micronutrients. They found that plant-based replacements could produce two- to 20-fold more protein per acre.

The most dramatic results were obtained for beef. The researchers compared it with a mix of crops – soya, potatoes, cane sugar, peanuts and garlic – that deliver a similar nutritional profile when taken together in the right proportions. The land area that could produce 100 grams of protein from these crops would yield only four grams of edible protein from beef. In other words, using agricultural land for producing beef instead of replacement crops results in an opportunity food loss of 96 grams – that is, a loss of 96% – per unit of land. This means that the potential gain from diverting agricultural land from beef to plant-based foods for human consumption would be enormous.

The estimated losses from failing to replace other animal-based foods with nutritionally similar crops were also huge: 90% for pork, 75% for dairy, 50% for poultry and 40% for eggs – higher than all conventional food losses combined.

“Opportunity food loss must be taken into account if we want to make dietary choices enhancing global food security,” said Milo.

Milo’s research is supported by the Mary and Tom Beck Canadian Centre for Alternative Energy Research, which he heads; the Zuckerman STEM Leadership Program; Dana and Yossie Hollander; and the Larson Charitable Foundation. Milo is the incumbent of the Charles and Louise Gartner Professorial Chair.

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

Getting closer look at Jupiter

This JunoCam image highlights Oval BA. (photo from nasa.gov)

The U.S. National Aeronautics and Space Administration (NASA) recently released the first findings of the Juno research spacecraft, which entered Jupiter’s atmosphere last year.

The Weizmann Institute of Science’s Dr. Yohai Kaspi is a senior member of the Juno mission team. The reason why this research is so important, he said, is because it will allow us to better understand how the solar system was formed.

“To do that, we really need to understand Jupiter and how it was formed because, then, we can understand earth, in sequence,” said Kaspi.

photo - Dr. Yohai Kaspi of the Weizmann Institute of Science — Dr. Yohai Kaspi of the Weizmann Institute of Science. *(photo from WIS)*

For Kaspi, the fascination with space came at the early age of 7, when his dad shared some pictures of the Voyager I and II and took him stargazing. His interest grew from there, including when he was navigating in the Negev while in the Israel Defence Forces.

“My hobby growing up was competitive sailing,” said Kaspi. “That drew my interest into meteorology and understanding why the wind blows the way it does. Growing up in Nahariya, which borders Lebanon … all kinds of stuff [are] coming from Lebanon – currents, trash. It was very obvious where the wind or current was coming from and that connected to sailing.”

Kaspi studied math and physics at Hebrew University before heading to the United States, seeking adventure and a doctorate at Massachusetts Institute of Technology. Soon after, he was recruited to be a professor at the Weizmann Institute of Science.

While at MIT, Kaspi became connected to the Juno mission, developing instruments to help measure atmospheric conditions on Jupiter.

“I was interested in space and the weather,” said Kaspi. “I studied meteorology, as it kind of brings them together … [with] planetary science. We have planets, which resemble earth in some aspects, but we don’t understand their features and circulation.”

While Jupiter is by far the biggest planet in the solar system (11 times the diameter of earth) and has the greatest mass (300 times that of earth), it is a gas planet (i.e. it has no liquid or solid parts). Kaspi has studied Jupiter’s different weather zones and deltas.

“I developed a theory for understanding how deeply they extend,” said Kaspi. “When you look at Jupiter, you have this red and white belt, or zone. That’s all at the cloud level, so it condensates at the same temperature. But, we have no information what’s happening underneath them. What we needed was a global way to survey what was happening underneath the cloud layer. And that’s exactly what Juno is.

“During my PhD, I developed a new method to relate between the gravity field of the planet and the flows underneath this cloud layer. To understand Jupiter, we need to understand what’s happening in its interior.”

Kaspi has been involved with Juno since 2008, along with 30 to 40 other scientists who form the core of the mission, developing and designing the experiments, and interpreting the data.

photo - This enhanced colour view of Jupiter’s south pole was created by citizen scientist Gabriel Fiset using data from the JunoCam on NASA’s Juno spacecraft — This enhanced colour view of Jupiter’s south pole was created by citizen scientist Gabriel Fiset using data from the JunoCam on NASA’s Juno spacecraft. *(photo from nasa.gov)*

“We’re trying to deduce the depths of the flows from the gravity measurements of the planet,” explained Kaspi. “The purpose is to see what’s happening inside the planet. It has nine instruments and each one probes in different ways what is happening in the planet’s interior.

“One is a gravity instrument…. We send a beam from the spacecraft to earth. The beam travels 800 million kilometres and reaches earth. A desert in California captures that beam.

“We try to see the accelerations and decelerations of the spacecraft around the planet … trying to understand … the flow field and the gravity field of Jupiter.”

It was only when we first saw earth from space that we were able to understand the changing atmospheric conditions that are part of what is largely considered part of climate change, said Kaspi.

“We’d be able to understand how the solar system was formed, including earth,” he said of one of the project’s possible results. “For example, it’s really important for us to know if there’s a core inside Jupiter. A planet with a big or small core would have a different effect on the gravity field. When we measure the gravity field, we can deduce what’s happening deep inside the planet, which would lead us to different theories of how the solar system was formed.

“The connection to earth is we see the objects of Jupiter’s atmospheres … we don’t understand their strengths, how wide they are and how deep they are. We don’t have theories for that. If you want to have a good understanding of objects on earth, you have to look at the sister planet.”

The data-collecting portion of the Juno mission will come to a close at the end of this year. After 10 years of research and six orbits, the data will be analyzed to determine the direction of the mission going forward.

“We have already a lot of good data and we’re reaching a point where we can have significant results for understanding the structure, depths and composition of the atmosphere, but it’s a process,” said Kaspi. “Basically, we have one measurement every 53 days. So, every 53 days, I get my stuff and go to the U.S. and stay there for a week, analyzing the data and analyzing it for the rest of the 45 days, and then go back.”

Regardless of the results, Kaspi will continue the work he is doing at the Weizmann Institute on climate change and working on an instrument that will be sent to Jupiter on board the 2022 spacecraft being built by the European Space Agency.

“It will be the first Israeli instrument that will go beyond earth’s orbit,” said Kaspi. “That’s exciting. So, we’re involved in that and a variety of projects, trying to achieve fundamental understanding.”

As far as space exploration for the purpose of finding another planet fit for human dwelling, Kaspi said, “I’m just going to say that, if there is life in the solar system, it might be in the moons of Jupiter … because they have liquid water, a deep ocean, tens to hundreds of kilometres deep. Maybe there is life there.”

The public can follow the Juno mission on Facebook at facebook.com/nasajuno.

Rebeca Kuropatwa is a Winnipeg freelance writer.

Israel’s BDS website

Featured on israelbds.org are popular articles that describe the history of Israeli-international scientific cooperation, research that has resulted from that cooperation and the people involved, as well as links to scientific papers. (image from israelbds.org)

Building Dialogue through Science, or BDS, is the purpose of a new website, israelbds.org, which features the many and varied scientific studies that rely on close collaboration between Israeli researchers and those in different countries.

These studies range from the SESAME synchrotron, a Middle Eastern facility based in Jordan that serves life-sciences researchers from Egypt to Iran; efforts to discover the processes that lead to the stellar explosions known as supernovae, in which Israeli researchers are alerted to possible events in the California night sky; brain research; quantum physics studies; scientific archeology; and much more.

Featured on the website are popular articles that describe the history of Israeli-international scientific cooperation, research that has resulted from that cooperation and the people involved, as well as links to scientific papers.

“Building dialogue through science, rather than building walls, has always been our way of doing things,” said Weizmann Institute of Science president Prof. Daniel Zajfman. “If we are going to work against the other BDS [boycott, divest from and sanction Israel], we must do so with real information. That is the intent of the site we have created. When scientists cooperate in their research, they bring back to their countries an understanding of the ways people can work together on many levels – over and above the scientific – including respect for other cultures and a desire for peaceful coexistence. That is why we believe that cooperation between Israeli scientists and those in universities and research institutes around the globe must be preserved at all costs.”

The hope, indeed, is that anyone visiting the website will understand what the world stands to lose from cutting off ties to Israel’s researchers and preventing students and labs around the globe from benefiting from Israeli advances.

Valeria Ulisse, an Italian research student studying the development of the nervous system at the Weizmann Institute of Science sums it up: “In Italy, I was in a really good lab but I was missing something internally. I wanted to improve my knowledge, to start a new project, to change my life and I found the place to do it.”

Israeli science is open to collaboration with anyone, independent of their political opinions.

“Research thrives on the meeting of different worldviews, and it is important to preserve that freedom to meet and discuss, even with those with whom we don’t always agree,” said Zajfman.

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.