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Is There a Way to Stop Parkinson’s Disease at Its Source?

TAU Researchers discovered a potential new target for developing effective treatments for Parkinson’s disease.

Researchers at Tel Aviv University discovered a new factor in the pathology of Parkinson’s disease, which in the future may serve as a target for developing new treatments for this terrible ailment, affecting close to 10 million people worldwide.

The researchers: “We found that a variant of the TMEM16F protein, caused by a genetic mutation, enhances the spread of Parkinson’s pathology through nerve cells in the brain”.

The study was led by Dr. Avraham Ashkenazi and PhD student Stav Cohen Adiv Mordechai from the Department of Cell and Developmental Biology at TAU’s Faculty of Medical and Health Sciences and the Sagol School of Neuroscience. Other contributors included: Dr. Orly Goldstein, Prof. Avi Orr-Urtreger, Prof. Tanya Gurevich and Prof. Nir Giladi from TAU’s Faculty of Medical and Health Sciences and the Tel Aviv Sourasky Medical Center, as well as other researchers from TAU and the University of Haifa. The study was backed by the Aufzien Family Center for the Prevention and Treatment of Parkinson’s Disease at TAU. The paper was published in the scientific journal Aging Cell.

Doctoral student Stav Cohen Adiv Mordechai explains: “A key mechanism of Parkinson’s disease is the aggregation in brain cells of the protein α-synuclein (in the form of Lewy bodies), eventually killing these cells. For many years, researchers have tried to discover how the pathological version of α-synuclein spreads through the brain, affecting one cell after another, and gradually destroying whole brain sections. Since α-synuclein needs to cross the cell membrane to spread, we focused on the protein TMEM16F, a regulator situated in the cell membrane, as a possible driver of this lethal process”.

α-synuclein spread in the mouse brain.

At first, the researchers genetically engineered a mouse model without the TMEM16F gene, and derived neurons from the brains of these mice for an in-vitro cellular model. Using a specially engineered virus, they caused these neurons to express the defective α-synuclein associated with Parkinson’s and compared the results with outcomes from normal brain cells containing TMEM16F. They found that when the TMEM16F gene had been deleted, the α-synuclein pathology spread to fewer healthy neighboring cells compared to the spread from normal cells. The results were validated in-vivo in a living mouse model of Parkinson’s disease.

TMEM16F Mutation Linked to Parkinson’s Risk in Ashkenazi Jews

In addition, in collaboration with the Neurological Institute at the Tel Aviv Sourasky Medical Center, the researchers looked for mutations (variants) in the TMEM16F gene that might increase the risk for Parkinson’s disease. Dr. Ashkenazi explains: “The incidence of Parkinson’s among Ashkenazi Jews is known to be relatively high, and the Institute conducts a vast ongoing genetic study on Ashkenazi Jews who carry genes increasing the risk for the disease. With their help, we were able to identify a specific TMEM16F mutation which is common in Ashkenazi Jews in general, and in Ashkenazi Parkinson’s patients in particular”. Cells carrying the mutation were found to secrete more pathological α-synuclein compared to cells with the normal gene. The researchers explain that the mechanism behind increased secretion has to do with the biological function of the TMEM16F protein: the mutation increases the activity of TMEM16F, thereby affecting membrane secretion processes.

Stav Cohen Adiv Mordechai: “In our study, we discovered a new factor underlying Parkinson’s disease: the protein TMEM16F, which mediates secretion of the pathological α-synuclein protein through the cell membrane to the cell environment. Picked up by healthy neurons nearby, the defective α-synuclein forms Lewy bodies inside them, and gradually spreads through the brain, damaging more and more brain cells. Our findings mark TMEM16F as a possible new target for the development of effective treatments for Parkinson’s disease. If, by inhibiting TMEM16F, we can stop or reduce the secretion of defective α-synuclein from brain cells, we may be able to slow down or even halt the spread of the disease through the brain”.

Dr. Ashkenazi emphasizes that research on the new Parkinson’s mechanism has only begun, and quite a number of questions still remain to be explored: Does inhibiting TMEM16F actually reduce the symptoms of Parkinson’s disease? Does the lipid composition of cell membranes play a part in spreading the disease in the brain? Is there a link between mutations in TMEM16F and the prevalence of Parkinson’s in the population? The research team intends to continue the investigation in these directions and more.

How Does the Brain Keep Calm?

New Insight into Brain Stability: The Key Role of NMDA Receptors

Researchers at Tel Aviv University have made a fundamental discovery: the NMDA receptor (NMDAR)—long studied primarily for its role in learning and memory—also plays a crucial role in stabilizing brain activity. By setting the “baseline” level for activity in neural networks, the NMDAR helps maintain stable brain function amidst continuous environmental and physiological changes. This discovery may lead to innovative treatments for diseases linked to disrupted neural stability, such as depression, Alzheimer’s disease, and epilepsy.

The study was led by Dr. Antonella Ruggiero, Leore Heim, and Dr. Lee Susman from Prof. Inna Slutsky’s lab at the Faculty of Medical and Health Sciences at Tel Aviv University. Prof. Slutsky, who is also affiliated with the Sagol School of Neuroscience, heads the Israeli Society for Neuroscience and directs the Sieratzki Institute for Advances in Neuroscience. Additional researchers included Dr. Ilana Shapira, Dima Hreaky, and Maxim Katsenelson from the Faculty of Medical and Health Sciences at Tel Aviv University, and Prof. Kobi Rosenblum from the University of Haifa. The study was published in the prestigious journal Neuron.

“In recent decades, brain research has mainly focused on processes that allow information encoding, memory, and learning, based on changes in synaptic connections between nerve cells”, says Prof. Slutsky.

“But the brain’s fundamental stability, or homeostasis, is essential to support these processes. In our lab, we explore the mechanisms that maintain this stability, and in this study, we focused on the NMDAR—a receptor known to play a role in learning and memory”, Slutsky continues.

This comprehensive project used three primary research methods: electrophysiological recordings from neurons in both cultured cells (in vitro) and living, behaving mice (in vivo) within the hippocampus, combined with computational modeling (in silico). Each approach provided unique insights into how NMDARs contribute to stability in neural networks.

Dr. Antonella Ruggiero studied NMDAR function in cultured neurons using an innovative technique called “dual perturbation”, developed in Prof. Slutsky’s lab. “First, I exposed neurons to ketamine, a known NMDAR blocker”, she explains. “Typically, neuronal networks recover on their own after disruptions, with activity levels gradually returning to baseline due to active compensatory mechanisms. But when the NMDAR was blocked, activity levels stayed low and didn’t recover. Then, with the NMDAR still blocked, I introduced a second perturbation by blocking another receptor. This time, the activity dropped and recovered as expected, but to a new, lower baseline set by ketamine, not the original level”. This finding reveals the NMDAR as a critical factor in setting and maintaining the activity baseline in neuronal networks. It suggests that NMDAR blockers may impact behavior not only through synaptic plasticity but also by altering homeostatic set points.

Building on this discovery, Dr. Ruggiero sought to uncover the molecular mechanisms behind the NMDAR’s role in tuning the set point. She identified that NMDAR activity enables calcium ions to activate a signaling pathway called eEF2K-BDNF, previously linked to ketamine’s antidepressant effects.

How NMDARs Set the Brain’s Activity Baseline

Leore Heim investigated whether the NMDAR similarly affects baseline activity in the hippocampus of living animals. A major technical challenge was administering an NMDAR blocker directly to the hippocampus without affecting other brain areas, while recording long-term activity at the individual neuron level. “Previous studies often used injections that delivered NMDAR blockers across the entire brain, leading to variable and sometimes contradictory findings,” he explains. “To address this, I developed a method combining direct drug infusion into the hippocampus with long-term neural activity recording in the same region. This technique revealed a consistent decrease in hippocampal activity across states like wakefulness and sleep, with no compensatory recovery as seen with other drugs. This strongly supports that NMDARs set the activity baseline in hippocampal networks in living animals”.

Mathematician Dr. Lee Susman created computational models to answer a longstanding question: Is brain stability maintained at the level of the entire neural network, or does each neuron individually stabilize itself? “Based on the data from Antonella and Leore’s experiments, I found that stability is maintained at the network level, not within single neurons,” he explains. “Using models of neural networks, I showed that averaging activity across many neurons provides computational benefits, including noise reduction and enhanced signal propagation. However, we need to better understand the functional significance of single-neuron drift in future studies”.

Prof. Slutsky adds: “We know that ketamine blocks NMDARs, and in 2008, it was FDA-approved as a rapid-acting treatment for depression. Unlike typical antidepressants like Cipralex and Prozac, ketamine acts immediately by blocking NMDARs. However, until now, it wasn’t fully understood how the drug produced its antidepressant effects. Our findings suggest that ketamine’s actions may stem from this newly discovered role of NMDAR: reducing the activity baseline in overactive brain regions seen in depression, like the lateral habenula, without interfering with homeostatic processes. This discovery could reshape our understanding of depression and pave the way for developing innovative treatments”.

Eyes Wide Shut: Bats Can Navigate Long Distances Using Sound Alone

Researchers found that bats can create a mental “sound map” of their environment.

A new study by Tel Aviv University and the Steinhardt Museum of Natural History has proven, for the first time, that bats can navigate in nature over many kilometers using only echolocation, without relying on other senses. The researchers explain: “It’s well-known that bats are equipped with a natural sonar, allowing them to emit sound waves that bounce back from nearby objects, helping them navigate. However, it’s also known that bats use their sense of sight during flight. Laboratory studies have shown that bats can navigate within enclosed spaces using only echolocation — but sonar ‘sees’ only about 10 meters ahead, so what happens under natural conditions, in open areas stretching over many kilometers? Can bats rely solely on echolocation for long-distance navigation?” In this study, that question was explored in depth for the first time.

They Follow the Echo

The research was led by Prof. Yossi Yovel of Tel Aviv University’s School of Zoology, Sagol School of Neuroscience, and Steinhardt Museum of Natural History, along with Dr. Aya Goldshtein, formerly a doctoral student of Prof. Yovel and currently a researcher at the Max Planck Institute in Germany. Additional partners from Tel Aviv University included Prof. Sivan Toledo of the Blavatnik School of Computer Science; Xing Chen, Dr. Eran Amichai, and Dr. Arjan Boonman of the School of Zoology; and Lee Harten of the Sagol School of Neuroscience. Prof. Ran Nathan and Dr. Yotam Orchan of the Hebrew University and Prof. Iain Couzin of the Max Planck Institute in Germany also participated in the study, which was published in the journal Science.

The innovative research carried out over six years, utilized a unique tracking system installed in Israel’s Hula Valley. Using this GPS-like technology, the researchers could track the flight of tiny bats from the species known as Kuhl’s pipistrelle, each weighing only six grams —— the smallest mammal ever to be monitored in this way.

For the study, the researchers collected around 60 bats from their roost in the Hula Valley area and moved them about three kilometers away from the roost — still within their familiar habitat. A tag was attached to each bat, and the eyes of some were covered with a cloth strip, temporarily preventing them from seeing during flight, though they could remove the covering with their feet upon landing. In addition, the researchers employed techniques to temporarily disrupt the bats’ sense of smell and magnetic sense, thereby creating conditions in which they would be able to find their way home using only echolocation. Remarkably, the bats managed to return to their roost without difficulty.

In the second phase, the researchers built a computerized acoustic model of the bats’ natural environment in the Hula Valley. Prof. Yovel explains: “This model is based on a 3D map of the area where the bats navigate, reflecting the echoes that the bat hears as it uses echolocation to journey through its surroundings. In examining the bats’ flight paths, we discovered that they choose routes where the echoes contain a lot of information, which helps them navigate. For example, an area rich in ​​vegetation, such as bushes and trees, returns echoes with more information than an open field, making bats less likely to fly over open terrain. We also found that some areas are characterized by distinct echoes, which are picked up by the bats. These findings strengthened our hypothesis that in any given area, bats know where they are based on the echoes. The bats effectively create an acoustic map in their head of their familiar environment, which includes a variety of active ‘sound landmarks’ (echoes) — just as every sighted person has a visual map of their everyday surroundings”.

פרופ' יוסי יובל

Hyperbaric Oxygen Therapy: A Promising Treatment for PTSD Symptoms

Biological damage in PTSD sufferers can be treated with a specialized protocol.

Researchers at Tel Aviv University and the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center have demonstrated that hyperbaric oxygen therapy (HBOT) improves the condition of PTSD sufferers who have not responded to psychotherapy or psychiatric medications. The researchers: “Our unique therapeutic protocol affects the biological brain ‘wound’ associated with PTSD, and effectively reduces typical symptoms such as flashbacks, hypervigilance, and irritability. We believe that our findings give new hope to millions of PTSD sufferers and their families, all over the world”.

The study was led by Prof. Shai Efrati and Dr. Keren Doenyas-Barak from the Faculty of Medical and Health Sciences at Tel Aviv University and the Sagol Center for Hyperbaric Medicine and Research at the Shamir Medical Center. Other contributors include Dr. Ilan Kutz, Gabriela Levi, Dr. Erez Lang, Dr. Amir Asulin, Dr. Amir Hadanny, and Dr. Ilia Beberashvili from the Shamir Medical Center, and Dr. Kristoffer Aberg and Dr. Avi Mayo from the Weizmann Institute. The paper was published in The Journal of Clinical Psychiatry.

“At present, we treat hundreds of PTSD sufferers every day”

Prof. Efrati: “Due to our unfortunate circumstances, Israel has become a global leader in the field of PTSD. Before the Hamas attack on Oct. 7, 2023, approximately 6,000 IDF veterans had been recognized as PTSD sufferers, with many others, both soldiers and citizens, not yet acknowledged by the authorities. Following Oct. 7 and the ensuing war, these numbers have risen sharply. Tens of thousands of soldiers, and much larger numbers of civilians, are likely to be diagnosed with PTSD. The world-leading Sagol Center for Hyperbaric Medicine, the largest of its kind in the world, is rising to the challenge – with a comprehensive therapeutic array comprising hyperbaric facilities combined with diverse mental health professionals, psychologists and psychiatrists. At present, we treat hundreds of PTSD sufferers every day, aiming to reach one thousand patients per year”.

Dr. Doenyas-Barak: “PTSD (Post-Traumatic Stress Disorder) is defined as the mental outcome of exposure to a life-threatening event. About 20% of those who have undergone such an experience will develop PTSD, which can lead to substantial social, behavioral, and occupational dysfunctions. In extreme cases, the disorder can severely impact their quality of life, family life, and professional performance. Symptoms include a range of emotional and cognitive changes, nightmares and flashbacks, hypervigilance, irritability, and avoidance – so as not to trigger traumatic experiences. In many cases, PTSD is resistant to psychotherapy and common psychiatric medications. Past studies on therapy-resistant sufferers have found changes in the structure and function of brain tissues, or a ‘biological wound’ that explains such treatment resistance. In our study, we wanted to determine whether hyperbaric therapy can help these patients”.

Testing HBOT for PTSD Relief

The study, which began in 2019 and ended in the summer of 2023, included 98 male IDF veterans diagnosed with combat-associated PTSD, who had not responded to either psychotherapy or psychiatric medications. Participants were divided into two groups: one group received HBOT treatment, breathing pure high-pressure oxygen, while the other underwent the same procedure, but received a placebo treatment, breathing regular air. 28 members of each group completed the process and the following evaluation.

Dr. Doenyas-Barak: “The HBOT was administered in accordance with a unique treatment protocol developed at our Center. Every patient is given a series of 60 two-hour treatments in our hyperbaric chamber, during which they are exposed to pure 100% oxygen at a pressure of 2 atmospheres (twice the normal air pressure at sea level). Our protocol specifies alternately breathing oxygen and regular air: every 20 minutes the patient removes the oxygen mask and breathes regular air for five minutes. The drop in oxygen level, at the tissue level, activates healing processes and thus enhances the therapeutic effect”.

Functional MRI before and after HBOT  Photo credit: The Shamir Medical Center.

Functional MRI before and after HBOT. Photo credit: The Shamir Medical Center.

The results were encouraging, with improvements observed both at the clinical level and in fMRI imaging.  The group that received hyperbaric therapy showed improved connectivity in brain networks, alongside a decline in all typical PTSD symptoms. In the placebo group, on the other hand, no change was observed in either the brain or clinical symptoms. Prof. Efrati: “Our study demonstrated that HBOT induces biological healing in the brain of PTSD sufferers. Curing the biological wound also impacts clinical symptoms. We believe that HBOT, based on the special protocol we have developed, can bring relief to numerous PTSD sufferers worldwide, allowing them to resume a normative life in their community and family”.

Prof. Efrati emphasizes:

“Patients suffering from PTSD should undergo HBOT only at professional hyperbaric centers, where treatment is delivered by multidisciplinary teams experienced in trauma care. Unsupervised, private hyperbaric chambers are unable to provide a proven, effective protocol. Additionally, patients must receive a thorough professional evaluation to ensure they are suitable for HBOT and to determine what additional support is needed throughout their treatment journey”.

Israel’s Ministry of Defense funds HBOT for veterans who need it.

Buzzed but Never Tipsy: Hornets’ Remarkable Alcohol Tolerance

Oriental hornets are the only animals able to drink unlimited amounts of alcohol.

A new study from the School of Zoology  and the Steinhardt Museum of Natural History  at Tel Aviv University has revealed that the Oriental hornet is the only known animal capable of chronically consuming alcohol in high concentrations with almost no negative effects on its health or lifespan. The research team says, “This is a remarkable animal that shows no signs of intoxication or illness even after ingesting huge amounts of alcohol.”

The research was conducted under the leadership of postdoctoral fellow Dr. Sofia Bouchebti from Prof. Eran Levin’s laboratory at Tel Aviv University’s School of Zoology and the Steinhardt Museum of Natural History. The study was published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS).

The researchers explain that alcohol is commonly produced in nature through the breakdown of sugars by yeasts and bacteria, primarily found in ripe fruits and nectar. Although alcohol contains nearly twice the amount of energy as sugar, it is toxic to most animals — including us humans — with occasional consumption, and especially with chronic use. Among the animals known to consume alcohol are fruit flies, which show signs of alcohol poisoning even at relatively low concentrations, and treeshrews — mammals native to East Asia that feed on ripe, alcohol-rich fruits — who show symptoms such as fatty liver and other effects indicative of alcoholism after consuming low concentrations of alcohol continuously for several days.

As for humans, many of us like consuming alcohol. Humans domesticated the wine grape around 10,000 years ago, and compared to other animals, we can tolerate and often enjoy consuming relatively high amounts of alcohol. However, as we know, alcohol has significant effects on behavior, cognition, and, of course, health, with a host of diseases linked to its consumption.

Hornets Can Handle Their Liquor

In the new study, the research team tested the Oriental hornet’s ability to consume alcohol and break it down. Dr. Bouchebti explains: “The hornets naturally store yeasts in their digestive system, which provides them with a unique environment that allows the yeast to develop and reproduce, creating new strains. One explanation is that hornets transfer yeasts to fruits, which indirectly contributes to the production of wine. In our study, we labeled the alcohol consumed by the hornets with a heavy carbon isotope. As the alcohol is metabolized, it breaks down into carbon dioxide, which is exhaled. By measuring the amount of labeled carbon dioxide emitted, we were able to estimate the speed at which the alcohol was broken down. The findings were surprising; we were amazed to see the rapid rate at which the hornets metabolized the alcohol”.

In the next stage, the researchers sought to determine whether the Oriental hornet ever becomes intoxicated. Does increased alcohol consumption affect their behavior, for example causing aggression or impacting their nest-building abilities? Here too, the findings were surprising: even when consuming high concentrations of alcohol (80 percent alcohol as the sole source of nutrition) there was no noticeable effect on the hornets’ behavior. In the final phase of the study, the researchers tested whether alcohol had any impact on the hornets’ lifespan and health. Once again, they were amazed to discover that no differences were found between the lifespan of hornets that consumed only alcohol for their entire lives (three months) and hornets that consumed sugar water.

No Hangovers Here

Prof. Levin concludes: “To the best of our knowledge, Oriental hornets are the only animal adapted to consuming alcohol as a metabolic fuel. They show no signs of intoxication or illness, even after chronically consuming huge amounts of alcohol, and they eliminate it from their bodies very quickly. In a bioinformatics analysis of the Oriental hornet’s genome, conducted by Prof. Dorothee Huchon, it was discovered that the hornet possesses several copies of the gene responsible for producing the enzyme that breaks down alcohol; this genetic adaptation may be related to their incredible ability to handle alcohol. We propose that the ancient relationship between hornets and yeast led to the development of this adaptation. Furthermore, while alcohol-related research is highly advanced, with 5.3 percent of deaths in the world linked to alcohol consumption, we believe that, following our research, Oriental hornets could potentially be used to develop new models for studying alcoholism and the metabolism of alcohol”.

Chemistry Researchers Awarded Prestigious ERC Synergy Grant

For research on electromagnetic impacts in molecular systems under strong light-matter coupling.

The European Research Council (ERC) has announced the results of the 2024 ERC Synergy Grant Call. Among the funded projects is an international collaboration, coordinated by Tel Aviv University researchers and titled “Unravelling the Mysteries of Vibrational Strong Coupling” (UNMYST). The prestigious ERC Synergy grants are awarded to leading researchers in their fields across all areas of science, and it is intended to promote groundbreaking interdisciplinary research.

The UNMYST project is an international collaboration between leading experimental and theoretical groups, including Dr. Tal Schwartz and Prof. Sharly Fleisher from the School of Chemistry at Tel Aviv University, Prof. Abraham Nitzan, an emeritus of the School of Chemistry at Tel Aviv University and a Donner Professor of Physical Sciences in University of Pennsylvania, Prof. Thomas Ebbesen and Cyriaque Genet from the University of Strasbourg, France, Prof. Angel Rubio and Dr. Michael Ruggenthaler from the Max Planck Institute for the Structure and Dynamics of Matter, Germany, and Dr. Dominik Sidler from the Paul Scherrer Institute in Switzerland.

According to the project coordinator Dr. Tal Schwartz, the UNMYST project will explore how tailoring the electromagnetic environment influences chemical and physical processes in molecular systems in the so-called “strong light-matter coupling” regime. The researchers anticipate that the results of the project will establish fundamental insights into such novel phenomena, which will lead to future breakthroughs with far-reaching implications for chemistry and materials sciences.

A Letter from TAU President Welcoming the New Academic Year

“May the hostages come back, the wounded heal, and the displaced return to their homes”.

This week, we begin the 2024-5 academic year, against the backdrop of the bloody war that rages on, and while we still lack a clear sense of how this war will unfold, particularly in relation to Iran.

The anguish over the hostages weighs heavily on us all. It’s hard to believe that over a year after the horrific disaster of October 7, many hostages are still languishing in the hellish tunnels of Gaza, with the bodies of many others held there as bargaining chips. We cannot win this war without bringing everyone home. Added to this is the daily sorrow and mourning for our soldiers, including members of our university community, who have fallen or been injured while defending us, as well as for the civilians who have fallen victim to terrorist acts across Israel. Our concern for the soldiers on the front lines and the tens of thousands of Israelis in the South and North–who either remain vulnerably in their homes or were displaced by circumstances–is unrelenting.

Yet, we have no other country, and fight for it we must. This is what the parents and grandparents of many of us did even before the establishment of Israel, and now it’s our turn. Our extraordinary young generation, with so many risking their lives on the battlefield, places a weighty responsibility on us, the older generation. What are we doing, as a university, and what more must we do in this crucial period?

One of our primary tasks, both last year and this year, is to do everything in our power to ensure that the reservist soldiers studying with us, as well as students who are spouses of soldiers, can complete the academic year successfully. Last year, we provided financial, academic, and emotional support and we will continue to do so this year as well. The emergency fund we established with the help of friends of the university in Israel and around the world has greatly assisted us in this endeavor.

Second, we succeeded last year in containing tensions on campus triggered by the war while maintaining a democratic space and protecting the human and civil rights of everyone. Members of our university community, Jews and Arabs, left-leaning and right-leaning, are equally dear to us. Open and free discussion on any topic is the essence of academia, and we will uphold this principle this year as well.

Third, a primary mission we are focused on is bringing as many Israeli researchers studying abroad back to Tel Aviv University as we have done in previous years. These researchers represent the next generation of academia; they embody the scientific and humanistic pursuits without which we have no future. Israel may seem less attractive to some of them at present, but I am confident that we will weather this crisis and emerge stronger.

Fourth, the growing boycott of Israeli academia worldwide (BDS) affects us all. Universities across the country have united and are working collaboratively to mitigate the impact of the boycott through legal and other means. We’ve had some successes, but there is still a long way to go.

Fifth, from October 7 to this day, the university–as an institution and as a community–has been involved in numerous volunteer activities. Days after October 7, our community members volunteered in the South and North, both in their areas of expertise and in agriculture and other manual work. We will continue to do so this coming year, hopefully in collaboration with local authorities in the South and North. A few months after the war broke out, we established the Post-Trauma Center, treating hundreds of people, both civilians and soldiers. Here, too, the generous financial support of our friends in Israel and abroad has been invaluable.

Sixth, we will continue to defend academic freedom and the autonomy of universities in Israel against those who seek to harm them. Academic freedom is essential for free thought, intellectually challenging education, and groundbreaking research. Without these, we will become a third-world country. I assure you that I will protect our academic freedom as one of my most cherished values.

These are the special missions that characterize this period. But equally important:  last year, we carried on teaching and doing research as if – or almost as if – there were no war. We, the university and Israel as a whole, do not have the privilege to stop “producing” doctors, engineers, psychologists, social workers, scientists, and humanist intellectuals. Nor do we have the privilege to stop advancing research. This is the source of our resilience, the safeguard of our future, and we cannot forsake it, not in times of peace and certainly not in times of war.

I thank you all – academic and administrative staff – for your hard work this past year to meet the challenges we set for ourselves, and our friends in Israel and abroad – for your generous support of the University and Israel.  And to you, our students – thank you for your patience with us. We are doing our utmost so that you derive the maximum benefit, and hopefully some enjoyment, from studying at Tel Aviv University.

I wish you a successful year, and may peace and tranquility return to our land. May the hostages come back, the wounded heal, and the displaced return to their homes.

Yours always,

Ariel Porat

TAU President

TAU Breakthrough Reveals Mechanism That Eliminates Tumors

Researchers identified a mechanism that eliminates tumors—even those resistant to immunotherapy.

A technological breakthrough by medical researchers at Tel Aviv University enabled the discovery of a cancer mechanism that prevents the immune system from attacking tumors. The researchers were surprised to find that reversing this mechanism stimulates the immune system to fight the cancer cells, even in types of cancer considered resistant to prevailing forms of immunotherapy. The breakthrough was led by Prof. Carmit Levy, Prof. Yaron Carmi, and PhD student Avishai Maliah from TAU’s Faculty of Medical and Health Sciences. The paper was published in the leading journal Nature Communications.

Prof. Levy: “It all happened by coincidence. My lab studies both cancer and the effects of ultraviolet (UV) radiation from the sun on our skin and body – both of which are known to suppress the immune system. Cancer suppresses approaching immune cells and solar radiation suppresses the skin’s immune system. While in most cases, we cancer researchers worldwide focus on the tumor and look for mechanisms by which cancer inhibits the immune system, here we proposed a different approach: investigating how UV exposure suppresses the immune system and applying our findings to cancer. The discovery of a mechanism that inhibits the immune system opens new paths for innovative therapies”.

What Surprising Findings Emerged from the Research?

Prof. Levy adds: “With this idea in mind, I asked my colleague Prof. Yaron Carmi, a global expert on the immune system, to join the study. Avishai Maliah, an MD/PhD candidate in my lab, led the project. The first stage was a comprehensive investigation of changes in the skin induced by exposure to UV, using a mouse model. Avishai examined the behavior of dozens of proteins post-UV exposure and surprisingly discovered a significant rise in the level of a relatively unexplored protein called Ly6a. This unexpected finding led us to investigate further, to understand the protein function and whether it is involved in the immune suppression process”.

Prof. Carmi explains: “It’s important to understand a basic aspect of the immune system’s function. Our natural immune system is very efficient and very powerful, but it contains quite a few brakes and controls, to prevent overactivity that can cause autoimmune diseases – in which the body attacks itself. When our skin is exposed to UV radiation from the sun, our immune system responds immediately: blood vessels expand, DNA is repaired wherever possible, and cells with mutations are identified and removed. At the same time, a strong control system with numerous brakes is also activated to prevent overactivity”.

How Does UV Exposure Affect Immune Response?

Prof. Levy: “The use of sunlight to suppress autoimmune diseases of the skin – when the skin’s immune system overreacts – has been known for years. Phototherapy is basically the application of UV radiation to treat patients with autoimmune diseases, such as psoriasis, vitiligo and more, because ultimately UV suppresses the skin’s immune system”.

Avishai Maliah: “We found that after exposure to UV radiation, the immune system’s T cells – that play a critical role in fighting cancer – begin to express high levels of the protein Ly6a. We suspected that Ly6a serves as a brake through which UV inhibits the immune system, and that by releasing this brake, optimal activation of the immune system might be resumed”.

Prof. Levy: “We were surprised to discover that this protein, Ly6a, is also overexpressed in cancer tumors – apparently inhibiting T cells. Having found this in two types of cancer, melanoma skin cancer and colon cancer, we have reason to believe that the same thing happens in other cancers as well. Evidently, we have discovered a general mechanism through which cancer tumors desensitize the immune system. Avishai treated cancer with Ly6a antibodies, and amazingly the tumors were significantly reduced. Moreover, cancers resistant to known treatments reacted substantially to Ly6a antibodies”. The new discovery can have practical implications in immunotherapy – treating cancer by enhancing the response of the immune system.

Prof. Carmi: “Immunotherapy has revolutionized the treatment of cancer. However, about 50% of the patients do not respond to the currently prevailing treatment – the protein PD1. We discovered a new protein, Ly6a, and found that its antibody eradicated tumors in our model animals – even those resistant to PD1 therapy. We are currently working to translate our findings into a drug for human cancer patients, hoping to offer an effective new treatment”.

 

Prof. Beatriz Magaloni: 2024 BMI Prize Laureate

Congratulations to Prof. Magaloni on winning the esteemed 2024 BMI prize.

The Faculty of Social Sciences at Tel Aviv University has announced that it is awarding the 2024 BMI Prize to Prof. Beatriz Magaloni from Stanford University, in recognition of her significant contributions to the study of authoritarianism. This esteemed prize is presented annually by the The Boris Mints Institute for Strategic Policy Solutions to Global Challenges and highlights the impact of a senior researcher’s work in specific academic fields.

Prof. Beatriz Magaloni is a distinguished scholar in political science, renowned for her groundbreaking research on autocratic regimes and their electoral processes. She holds the position of Graham H. Stuart Professor of International Relations and is a Senior Fellow at the Freeman Spogli Institute for International Studies at Stanford University. Her work has become foundational in understanding multi-party autocracies, which are increasingly prevalent forms of governance globally.

Prof. Magaloni’s research addresses critical questions regarding why autocratic regimes opt for multi-party elections and the implications of these elections for democracy. She elucidates the nuanced threats posed by civilian leaders who ascend to power through electoral means rather than military coups, offering vital insights into electoral behavior and regime stability.

Throughout her career, Prof. Magaloni has published extensively in leading journals, including the American Political Science Review and World Development. Her work is widely assigned in graduate and undergraduate courses, shaping the academic agenda for studies in comparative politics.

The award will be presented to Prof. Magaloni at the joint BMI-University of Donja Gorica Conference in Podgorica, Montenegro, on November 25th.

For further information about Prof. Beatriz Magaloni and her research, visit her profiles on Stanford University and the Carnegie Endowment.

Let Them Migrate in Peace

Migratory birds in times of war.

Israel, a stopover for over 500 million migratory birds heading to warmer lands, has been at war on multiple fronts for a year. As these birds migrate south, they face not only the usual dangers but also added risks from fighter jets, missiles, and UAVs along their northern arrival routes and southern destinations.

Prof. Yossi Leshem from the School of Zoology at the George S. Wise Faculty of Life Sciences has studied birds, especially migratory ones, for over 50 years. He began tracking their flight paths in Israel 40 years ago using a glider, observing their spring migration from Egypt to Lebanon and autumn route southward. This work allowed him to map their arrival times, flight altitudes, and the effects of weather on their behavior.

Flying with the Birds (Photo: Eyal Bartov).

In the 1980s, he pioneered radar use in Israel to study bird migration, working with the Israeli Air Force to reduce mid-air collisions between military aircraft and birds. We asked him how the current conflict impacts migratory birds and whether solutions exist to protect both human and avian lives.

Can Radar Distinguish Between Birds and Aircraft?

“A radar is an electronic device that sends out electromagnetic waves. If there’s something in the air, the waves bounce back, indicating distance and azimuth. The larger the bird, the stronger the radar signal. Large birds like raptors, pelicans, storks, or cranes are at greater risk, posing the most significant danger to Air Force planes”, explains Prof. Leshem.

לעשות הכל כדי למנוע התנגשות אווירית איתם. שקנאים בתעופת "מבנה מכונס" בנדידת הסתיו (צילום: אהרון שמשון)

Doing everything to prevent an air collision with them. Pelicans in tight formation during their autumn migration (Photo: Aharon Shimshon).

“Today, it’s understood that larger birds generally fly over land to use thermals (warm air rising from the ground). Based on their speed, we can often identify flocks of birds. We can track migratory birds on radar up to 80-90 kilometers away”, says Prof. Leshem. However, since the war began and UAVs from Lebanon started appearing, distinguishing birds from hostile aircraft has become more challenging.

“During autumn, migration comes through Europe, Turkey, Lebanon, and down through Israel—the same route used by missiles and UAVs. They come from the same direction, height, and azimuth”. According to Prof. Leshem, this has led to four main challenges: additional pressure on air defense and the air force, which must quickly decide if there is a true threat or if cranes are merely passing by; stress for civilians prompted by alert systems when stork flocks fly overhead; harm to wildlife entering Israeli airspace; and substantial financial costs of interception missiles and air force resources”. Nonetheless, Prof. Leshem reveals that efforts are underway to develop a system that can differentiate between birds and UAVs, which will save countless bird lives.

מגינה על תושבי ישראל ומסוכנת לציפורים. מערכת כיפת ברזל

Protecting Israel’s Residents, Endangering Its Birds: The Iron Dome System.

How is the War Affecting Local Birds?

It’s not just migratory birds suffering from the consequences of war. Prof. Leshem leads a project in collaboration with the Ministry of Agriculture and the Society for the Protection of Nature, using barn owls and kestrels for natural rodent control in agricultural areas to reduce pesticide use. There are about 5,000 nesting boxes nationwide, supported by hundreds of farmers who receive professional assistance. The project now includes ten Middle Eastern countries and has recently welcomed Georgia, Ukraine, and Germany, fostering cross-border cooperation.

Prof. Leshem explains that barn owls typically lay between 5 to 12 eggs annually, depending on food availability. “However, the war has significantly reduced nesting and egg-laying in conflict zones in the north and south, where burned fields have impacted rodent populations. Fewer chicks this year will lead to a smaller barn owl population next year, resulting in long-term effects”.

מלכודת מוות למכרסמים - הפסקת אספקת מזון לעופות הדורסים. שדות שרופים ביישובי עוטף עזה

A Death Trap for Rodents – A Cut in Food Supply for Birds of Prey: Burned Fields in the Gaza Border Area.

Will the Impact on Birds Affect the Entire Ecological Balance?

“Absolutely, the impact on birds is affecting the entire ecological balance in several ways. From small songbirds to larger migratory birds like storks, each species plays a crucial role in the ecosystem. For example, the black-headed bunting migrates from this region to Africa in the fall, crossing the Sahara Desert, and depends on the insects in our fields and surroundings to build up enough fat reserves for the journey. If these fields aren’t providing enough food, the bunting may seek other locations, leading to an increase in insects in our agricultural areas, which can harm local crops”.

“Additionally, storks, which arrive here in large numbers and help control rodent populations by preying on voles in flooded fields, are essential for maintaining this balance. If these storks don’t arrive, farmers may face increased rodent populations, which can damage crops. So, if birds don’t receive the ecological support they need here, the local balance will likely shift significantly, bringing widespread environmental consequences for agriculture, species diversity, and our overall environmental health”, he explains.

בדרך לאפריקה עוצר לתדלק בישראל. גיבתון שחור ראש

On its way to Africa, stopping to refuel in Israel: the Black-headed Bunting.

Will Migration Patterns Shift Due to War?

“Migration has been occurring for hundreds of thousands of years, and it won’t change quickly,” assures Professor Leshem. “However, it could impact survival chances. In a typical winter, about 50,000 cranes spend the season in the Hula Valley, but last year only 15,000 arrived. Some birds, like storks, birds of prey, and pelicans, stop here for just a night or two to ‘refuel’ before continuing their journey. If they can’t land in their usual spots due to burned fields or are scared off by gunfire, they may need to find other locations. This search could decrease their chances of successfully reaching their destination, affecting the larger migration cycle”.

עוד יגיעו ימים יפים. עשרות אלפי עגורים חורפים באגמון החולה (צילום: שירז פשניסקי)

Perhaps there will still be beautiful days ahead. Thousands of cranes in the Hula Lake (Photo: Shiraz Pashinsky).

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