Newsroom – Page 17 – Australian Friends of Tel Aviv University

Destroying Cancer: new drug delivery system containing RNA therapy can target cancer cells in bone marrow

Written by AUFTAU on 31 July 2023. Posted in Newsroom.

Researchers at Tel Aviv University destroyed 90% of the multiple myeloma blood cancer cells under laboratory conditions, and 60% in human tissues taken from patients at Rabin Medical Center (Belinson Hospital), using an RNA-based drug delivered to the cells by targeted lipid nanoparticles.

The researchers developed lipid-based nanoparticles (similar to those used in the COVID-19 vaccine) containing RNA molecules that silence the gene CKAP5, encoding cytoskeleton-associated protein 5. With this protein inhibited the cancer cell is unable to divide, which essentially kills it. To avoid damaging noncancerous cells, the nanoparticles were coated with antibodies that guided them specifically to the cancer cells inside the bone marrow.

The breakthrough was achieved by a group of researchers from Tel Aviv University and the Rabin Medical Center, led by Prof. Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at the Shmunis School of Biomedicine and Cancer Research, also serving as TAU’s VP R&D, and by PhD student Dana Tarab-Ravski. The results were published in the leading journal Advanced Science.

Cover image for Advanced Science (credit: Ella Maru Studio)

“The targeted drug delivery system we developed is the first to effectively reach cancer cells inside the bone marrow.”

Dana Tarab-Ravski explains: “Multiple myeloma is a blood cancer usually found in the older population. While most blood cancers appear in the blood stream or lymph nodes and spread from there to the rest of the body, multiple myeloma cells appear and form tumors inside the bone marrow – and are therefore very hard to reach.”

The study’s findings are very encouraging: under laboratory conditions, where cells are grown in flasks, the nanoparticles developed by the researchers eradicated about 90% of the cancer cells. At the second stage, the new treatment was tested on cancer samples taken from multiple myeloma patients at the haemato-oncological ward of the Rabin Medical Center. The success rate in these samples was 60%. Testing the ability of the nanoparticles to reach the bone marrow in an animal model, the researchers found that after a single injection the RNA had penetrated to 60% of the multiple myeloma cancer cells in the bone marrow. Lastly, examining the therapeutic effectiveness of the nanoparticles in the animal model resulted in eradication of two thirds of the cancer cells, and the animals showed significant improvement in all clinical indicators.

“People with multiple myeloma suffer from severe pain in their bones, as well as anemia, kidney failure, and a weakened immune system,” says Tarab-Ravski. “There are many possible treatments for this disease, but after a certain period of improvement most patients develop resistance to the therapy and the disease relapses even more aggressively. Therefore, there is a constant need for developing new treatments for multiple myeloma. RNA-based therapy has a great advantage in this case because it can be developed very quickly. By simply changing the RNA molecule a different gene can be silenced each time, thereby tailoring the treatment to the progression of the disease and to the individual patient. The challenge in these treatments is to reach the right cells. Today RNA therapeutics are approved for treating a genetic liver disease and for vaccines injected into the muscle, as we saw with the COVID-19 vaccines. The drug delivery system we developed is the first that specifically targets cancer cells inside the bone marrow, and the first to show that silencing the expression of CKAP5 gene can be used to kill blood cancer cells.”

Prof. Dan Peer: “Our technology opens a new world for selective delivery of RNA medications and vaccines for cancer tumors and diseases originating in the bone marrow.”

The clinical team included Dr. Tamar Berger, Dr. Iuliana Vaxman and Prof. Pia Raanani from the Institute of Hematology, Rabin Medical Center, Beilinson Hospital. The research was funded by the the Boaz and Varda Dotan Hematologyoncology Center at Tel-Aviv University and by Lewis Trust for Blood Cancer Research awarded to D.P.

Stress Makes Vaccines Less Effective

Written by AUFTAU on 26 July 2023. Posted in Newsroom.

Researchers at Tel Aviv University demonstrated for the first time that there is a significant link between behavioral stress and the effectiveness of vaccines. They found that acute stress in lab models 9-12 days after vaccination increases antibody response to the vaccine by 70% compared to the unstressed control group. This, however, comes at the price of reduced antibody breadth, which results in diminished protection against the pathogen’s variants.

“Our study was the first to investigate the possible effects of acute stress. We found that this mental state has a dramatic impact – not only on the vaccine’s effectiveness, but also on how it works.” – Dr. Natalia Freund

The “Dramatic Impact” of Stress

The study was carried out in Tel Aviv University and led by Ph.D. student Noam Ben-Shalom from the lab of Dr. Natalia Freund at the Faculty of Medicine and Ph.D. student Elad Sandbank from the Neuro-immunology Lab of Prof. Shamgar Ben-Eliyahu at The School of Psychological Sciences and the Sagol School of Neuroscience. The paper was published on July 6th in the leading scientific journal Brain, Behavior, and Immunity.

Dr. Freund explains: “In this study we examined, for the first time, the correlation between stress and the body’s ability to develop an immune response following vaccination. The prevailing assumption is that the effectiveness of a vaccine is determined mainly by its own quality. However, over the years, professional literature has reported influences of other factors as well, such as the age, genetics, and microbiome of the outcomes of vaccination. Our study was the first to investigate the possible effects of acute stress. We found that this mental state has a dramatic impact – not only on the vaccine’s effectiveness, but also on how it works.”

Classical ‘Fight or Flight’ Response

Acute stress is a mental state caused by immediate threat (either real or imagined), involving the secretion of adrenaline and stimulation. In this study, Dr. Freund and her colleagues vaccinated mice with two different vaccines: the model protein Ovalbumin and a fragment of the SARS-CoV-2 spike protein also used in the COVID-19 vaccine. Nine days later, just as the adaptive immunity became active and the production of antibodies began, the mice were subjected to a widely used behavioral paradigm simulating acute stress. Two and a half weeks after exposure to stress, namely 30 days after vaccination, the level of antibodies in the blood of vaccinated animals that had experienced stress was 70% higher compared to the control group. This phenomenon was observed in animals vaccinated with either type of vaccine.

At the same time, the researchers discovered that the immune system of the animals that had experienced stress was not cross reactive to variants of the protein used in the vaccine. In other words, following stress the immune system was focused entirely on the original vaccine, showing no response to proteins that were only slightly different – such as variants of concern (VOC) of SARS-CoV-2.

Dr. Natalia Freund

“In general, the purpose of vaccination is not only protection against a specific pathogen, but also creating a long-lasting immunological memory for protection against future mutations of that pathogen.” – Dr. Natalia Freund

“Initially, we were surprised to find out that the response to the vaccine was much more effective in animals that had experienced stress,” says Dr. Freund, “we would have assumed just the opposite – that stressful situations would have a negative impact on the immune system. Nevertheless, with both types of vaccines, we observed a stronger immune response after stress, both in the blood and in B cells (the lymphocytes that produce antibodies) derived from the spleen and lymph nodes of the immunized mice. The enhancement of the antibodies’ activity following stress was mediated by the cellular receptor that identifies adrenaline – the beta2 adrenergic receptor. When we blocked this receptor, either pharmacologically or by means of genetic engineering, the effects of stress were completely eliminated. On the other hand, to our great surprise, the breadth of the immune response generated by the vaccine was reduced by about 50% following stress. In general, the purpose of vaccination is not only protection against a specific pathogen, but also creating a long-lasting immunological memory for protection against future mutations of that pathogen. In this sense, the vaccines appeared to lose much of their effectiveness after exposure to stress.”

According to the researchers, this is in fact a classical ‘fight or flight’ response, however this time demonstrated at the molecular level. During stress, the immune system produces large quantities of antibodies and stronger antibodies, to address the immediate infection, and this large energetic investment in the here and now comes at the expense of future immunological memory.

Does It Apply to Humans?

Dr. Freund adds: “In the second part of the study we wanted to test whether humans also display the post-stress immune impairment observed in vaccinated mice. For this purpose, we cultured B cells obtained from blood of people who had contracted COVID-19 in the first wave. We then induced stress in these cultures using an adrenaline-like substance that stimulates the beta2 adrenergic receptor, that was identified by us in the first part of the study as a mediator of the response to stress in cells that produce antibodies in mice. B cells express a very high level of these receptors, but until now the receptors’ role in producing antibodies was not known. In fact, it was unclear why these cells need the ability to respond to adrenaline.”

“We discovered that just like in mice, human cells also exhibit a zero-sum game between the intensity and breadth of the immune response. When the adrenaline receptor is activated during stress, the entire immune system is stimulated, generating antibodies that are 100-fold stronger than antibodies produced in cells that had not undergone stress. But here too, the response was narrower: the diversity of antibodies was reduced by 20-100%, depending on the individual from whom the cells were taken.

“Stress 9 to 12 days after vaccination, at the time when B cells are generating high affinity antibodies, enhances short-term immunity and damages long-term memory.” – Dr. Natalia Freund

RNA sequencing of the cells in which the beta 2 adrenergic receptor was activated, compared to regular cells, indicated that the receptor’s activation caused antibody-producing cells to work at maximum capacity (by activating the PI3 kinase protein and phosphorylation of AKT) – at the expense of antibody breadth and diversity.”

“From the evolutionary perspective,” concludes Dr. Freund, “stress can be caused by different factors. We tend to think of mental stress, but physical illness also causes a form of stress. When the body contracts a virus or bacteria it experiences stress, and signals to the immune system that the top priority is getting rid of the pathogen, while investing energy in long-term immunological memory is a second priority. Therefore, stress 9 to 12 days after vaccination, at the time when B cells are generating high affinity antibodies, enhances short-term immunity and damages long-term memory.”

Unearthing Ancient Intelligence

Written by AUFTAU on 23 July 2023. Posted in Newsroom.

A new study from Tel Aviv University and Tel-Hai College solves an old mystery: Where did early humans in the Hula Valley, in northern Israel, get flint to make the prehistoric tools known as hand axes? The researchers applied advanced methods of chemical analysis and AI to identify the geochemical fingerprints of hand axes from the Hula Valley’s oldest prehistoric sites, Ma’ayan Barukh and Gesher Benot Ya’aqov. Their findings indicate that the raw material came from exposures of high-quality flint in the Dishon Plateau, about 20km to the west, and hundreds of meters above the Hula Valley. The researchers: “Our findings indicate that these early humans had high social and cognitive abilities: they were familiar with their surroundings, knew the available resources, and made great efforts to procure the high-quality raw materials they needed. For this purpose, they planned and carried out long journeys, and transferred this essential knowledge to subsequent generations.”

“Our findings indicate that early humans were highly capable: they planned and implemented complex strategies and passed on essential information from one generation to the next.” – The researchers

Early Humans’ Versatile “Swiss Army Knife”

The study was led by Dr. Meir Finkel of the Department of Archaeology and Ancient Near East Cultures, Tel Aviv University and Prof. Gonen Sharon of the MA Program in Galilee Studies, Tel-Hai College, in collaboration with Prof. Erez Ben-Yosef, Tel Aviv University, Dr. Oded Bar and Dr. Yoav Ben Dor, the Geological Survey of Israel, and Ofir Tirosh, the Hebrew University. The paper was published in Geoarchaeology.

Dr. Finkel: “The Hula Valley, located along the Dead Sea Transform Rift, is well known for its many prehistoric sites, the oldest of which date back to 750,000 years before present (YBP). The valley offered early humans rich sources of water, vegetation, and game, right on the northward migration route from Africa – the Great African Rift Valley. These early inhabitants left behind them many artifacts, including thousands of hand axes – flint stones chiseled to fit the human hand. One of the earliest and most universal tools produced by humans, the hand axe may have served as a multipurpose ‘penknife’ for many different tasks, from cutting game meat to digging for water and extracting roots. It was used in many different parts of the Old World, in Africa, Asia, and Europe, for about 1.5 million years.”

“One of the earliest and most universal tools produced by humans, the hand axe may have served as a multipurpose ‘penknife’ for many different tasks, from cutting game meat to digging for water and extracting roots.” – Dr. Meir Finkel

In the present study the researchers looked for the source of the raw material used to produce thousands of hand axes found at two prehistoric sites in the Hula Valley: Gesher Benot Ya’aqov, dated to 750,000 YBP and Ma’ayan Barukh, dated to 500,000 YBP, both Acheulian. Prof. Sharon: “Approximately 3,500 hand axes were found scattered on the ground at Ma’ayan Barukh, and several thousands more were discovered at Gesher Benot Ya’aqov. The average hand axe, a little over 10cm long and weighing about 200g, was produced by reducing stones that are five times larger – at least 1kg of raw material. In other words, to make the 3,500 hand axes found at Ma’ayan Barukh alone, early humans needed 3.5 tons of flint. But where did they obtain such a huge amount of flint? Many researchers have tried to answer this question, but our study was the first to use innovative 21st century technologies: advanced chemical analysis and an AI algorithm developed specifically for this purpose.”

The Gesher Benot Ya’aqov area

20 Kilometer Hikes Across Diverse Terrain

The researchers took samples from 20 hand axes – 10 from Gesher Benot Ya’aqov and 10 from Ma’ayan Barukh, ground them into powder and dissolved the powder in acid in a clean lab. For each sample they measured the concentration of approximately 40 chemical elements, using an ICP-MS (inductively coupled plasma mass spectrometer), a state-of-the-art device that accurately measures the concentration of dozens of elements, down to a resolution of one particle per billion.

In addition, in order to locate possible flint sources available to the Hula Valley’s prehistoric inhabitants, the researchers conducted a field survey covering flint exposures in the Safed Mountains, Ramim Ridge, Golan Heights, and Dishon Plateau, as well as cobbles from streams draining into the Hula Valley: the Jordan, Ayun, Dishon, Rosh Pina, and Mahanayeem. This methodical survey was combined with a comprehensive literature review led by Dr. Bar of the Geological Survey of Israel. Flint samples collected from all potential sources were then analyzed using ICP-MS technology to enable comparison with the hand axes. A novel computational approach specially adapted by Dr. Ben Dor of the Geological Survey of Israel was used for this comparison.

Dr. Ben Dor: “The complex process, from collecting and preparing the samples to the chemical analysis, produced a very large amount of data for each sample. To enable optimal matching between data from the archaeological artifacts and data from the flint exposures, we developed a dedicated algorithm based on several computational steps, alongside machine learning models. Thus, we were able to classify the archaeological artifacts according to the database derived from the geological samples.”

“To procure suitable raw materials for producing their vital hand axes, [humans living in the Hula Valley hundreds of thousands of years ago] planned and carried out 20km hikes that included an ascent from 70 to 800 meters above sea level.” Prof. Erez Ben-Yosef

Dr. Finkel: “Through the computational process we discovered that all 20 archaeological artifacts were made of flint from a single source: the Dishon Plateau’s flint exposures dating back to the Eocene geological epoch, about 20km west of the Gesher Benot Ya’aqov and Ma’ayan Barukh sites. At the Dishon Plateau we also found a prehistoric flint extraction and reduction complex, indicating that the place served as a flint source for hundreds of thousands of years. In addition, we demonstrated that cobbles from streams draining into the Hula Valley were too small to be used as raw material for hand axes, ruling out this possibility.”

Prof. Ben-Yosef: “Our findings clearly indicate that humans living in the Hula Valley hundreds of thousands of years ago, probably hominids of the homo erectus species, possessed high cognitive and social capabilities. To procure suitable raw materials for producing their vital hand axes, they planned and carried out 20km hikes that included an ascent from 70 to 800 meters above sea level. Moreover, they passed on this important knowledge from one generation to the next, over many millennia. All these suggest a high level of sophistication and ability, which modern researchers do not usually attribute to prehistoric humans from such an early period.”

From left: Dr. Meir Finkel and Prof. Erez Ben Yosef

Barbie Buzz: Mattel CEO Shares Branding Wisdom with Tel Aviv University Students

Written by AUFTAU on 23 July 2023. Posted in Newsroom.

The movie Barbie, based on the iconic doll created by American toy company Mattel, premiered this weekend in movie theaters worldwide to much critical acclaim. The movie’s release marks a significant point in the transformation that the long-established company has undergone in recent years under the leadership of Ynon Kreiz, Mattel’s Chairman and CEO.

Ahead of the premier, Kreiz, a Tel Aviv University alumnus, met with the University’s students to discuss the power of transformative leadership and share his personal story. “It’s an honor and a privilege for me to speak here today, having come full circle,” he said.

Kreiz began his career in the world of media after completing his undergraduate studies at TAU’s Coller School of Management and an MBA at UCLA. “The studies at TAU were of the highest level—they prepared me for graduate school […] and helped me to continue the journey onwards from there,” Kreiz told his audience at the beginning of the talk, explaining the reasons he chose TAU after his military service.

“The studies at TAU were of the highest level—they prepared me for graduate school […] and helped me to continue the journey onwards from there.” – Ynon Kreiz

From Barbie the Doll to Barbie, the Movie

Kreiz went on to discuss the transformation that Mattel has undergone under his leadership in recent years, going from a manufacturer of toys to a media company that offers its well-known and beloved brands on a broad range of platforms. He emphasized that the key to success in leading a large towards change is the correct choice of the management team and creating an environment that enables the team to excel.

“No CEO can know everything in every area and take care of every issue,” he explained. “My most important function is to choose a strong management team, to lead them, to encourage them to respond quickly to events in the market, and to build together with them a flexible and fast-moving organization that will know how to compete and change. You have to believe in the talents of the team and let them work, but at the same time if you feel that something is not working – you have to make cuts quickly and not leave people in positions for which they are not suited.”

Ynon Kreiz met with TAU students to discuss the power of transformative leadership and share his personal story

“My most important function is to choose a strong management team, to lead them, to encourage them to respond quickly to events in the market, and to build together with them a flexible and fast-moving organization that will know how to compete and change.” – Ynon Kreiz

Kreiz was the fourth CEO at Mattel in almost five years, which indicated the difficulties the company experienced at the time, with years of stagnancy and heavy losses. “Mattel has strong brands. In the area of children’s toys it comes right after Disney in my opinion,” he said, “and my challenge was to lead it from being a company that perceives itself as a manufacturer of toys to being a company that manages brands; from a company that sells to customers, to a company that manages relations with supporters. We did it without giving up on the core business of toys, by expanding into television, movies, parks, and music, and in general into customer experiences based on our brands.”

Kriez discussed the organizational and structural challenges he and his management team faced, having to cut many workplaces, close factories and massively reorganize the company’s structure. “Yet we made sure to keep the morale of the employees who were retained high and committed to the new goals,” he said. “We did it by defining a clear and simple goal for the company: creating innovative and entertaining experiences for children. I cut down the vision statement of the company to a single page, so that every employee could relate to it. In addition, we gave the employees freedom and responsibility, for instance in choosing unlimited vacations for themselves, coordinated with the manager.”

According to Kreiz, another important message that he imprinted at Mattel was that alongside the financial goals, the company had to operate responsibly: “We have a real influence on society,” he said. “We work with children and we help in forming the future.”

The Personal Story

Kreiz also talked about what it takes to succeed in today’s business world. He said that one of the most important things he learned over the years was to be prepared to acknowledge his mistakes and to correct them quickly – without dwelling on the past. “You failed? Correct it and move on. And that also applies to success. I don’t think it is right to dwell too much on what has happened because time changes very quickly. The important thing is to focus on the present and plan for the future, in accordance with the current situation. You can’t win every battle. The important thing is to keep going.”

“It doesn’t matter what you are doing or at what level. You can always do things better, in a more innovative way. That’s the way to stand out and move forward.” – Ynon Kreiz

Kreiz said that despite his many years in the USA he still brings to his job traits that many perceive as Israeli. “I am a ‘tachles’ person–and you won’t find a word for it in English. The closest I can think of is ‘goal-oriented’. I strive to define goals and to work to achieve them, to make things happen. I don’t know if that’s because I am Israeli, but that’s the way I am.”

Kreiz recommended to students in the audience that they plan their future with a focus on innovation. “It doesn’t matter what you are doing or at what level. You can always do things better, in a more innovative way. That’s the way to stand out and move forward.”

Researchers Produce Highly Efficient, Low-cost “Green” Hydrogen

Written by AUFTAU on 17 July 2023. Posted in Newsroom.

Tel Aviv University researchers have achieved a groundbreaking milestone by successfully producing highly efficient and low-cost “green” hydrogen. By harnessing the power of green electricity and utilizing a highly efficient biocatalyst, this innovative process generates hydrogen without any air pollution.

Hydrogen plays a vital role as raw material in both agriculture and industry. However, most of the hydrogen produced globally, approximately 95%, falls in the “black” or “gray” category. These types of hydrogen are derived from coal or natural gas, emitting a significant 9-12 tons of carbon dioxide for every ton of hydrogen produced.

Over 90% Efficiency

The new method was developed by doctoral student Itzhak Grinberg and Dr. Oren Ben-Zvi, under the guidance of Prof. Iftach Yacoby of the School of Plant Sciences and Food Security at the Faculty of Life Sciences and Prof. Lihi Adler-Abramovich of the School of Dental Medicine and the Center for Nanoscience and Nanotechnology. The promising research results were published in the prominent journal Carbon Energy, focusing on advanced materials and technology for clean energy and CO2 emission reduction.

“Hydrogen is very rare in the atmosphere,” explains Itzhak Grinberg, “although it is produced by enzymes in microscopic organisms, which receive the energy for this from photosynthesis processes. In the lab, we ‘electrify’ those enzymes, that is, an electrode provides the energy instead of the sun. The result is a particularly efficient process, with no demand for extreme conditions, that can utilize electricity from renewable sources such as solar panels or wind turbine. However, the enzyme ‘runs away’ from the electric charge, so it needs to be held in place through chemical treatment. We found a simple and efficient way to attach the enzyme to the electrode and utilize it.”

The researchers used a hydrogel (a water-based gel) to attach the enzyme to the electrode and were able to produce green hydrogen using a biocatalyst, and with over 90% efficiency; that is, over 90% of the electrons introduced into the system were deposited in the hydrogen without any secondary processes.

“We hope that in the future, it will be possible to employ our method commercially, to lower the costs, and to make the switch towards using green hydrogen in industry, agriculture, and as a clean energy source.” – Dr. Oren Ben-Zvi

Prof. Iftach Yacoby explains that, “The material of the gel itself is known, but our innovation is to use it to produce hydrogen. We soaked the electrode in the gel, which contained an enzyme for producing hydrogen, called hydrogenase. The gel holds the enzyme for a long time, even under the electric voltage, and makes it possible to produce hydrogen with great efficiency and at environmental conditions favorable to the enzyme — for example, in salt water, in contrast to electrolysis, which requires distilled water.

Prof. Lihi Adler-Abramovich adds: “Another advantage is that the gel assembles itself — you put the material in water, and it settles into nanometric fibers that form the gel. We demonstrated that these fibers are also able to stick the enzyme to the electrode. We tested the gel with two other enzymes, in addition to the hydrogenase, and proved that it was able to attach different enzymes to the electrode.”

“Today, ‘green’ hydrogen is produced primarily through electrolysis, which requires precious and rare metals such as platinum along with water distillation, which makes the green hydrogen up to 15 times more expensive than the polluting ‘grey’ one, says Dr. Oren Ben-Zvi. “We hope that in the future, it will be possible to employ our method commercially, to lower the costs, and to make the switch towards using green hydrogen in industry, agriculture, and as a clean energy source.”

Researchers Induce Cancer Cell “Suicide”

Written by AUFTAU on 17 July 2023. Posted in Newsroom.

For the first time in the world: researchers at Tel Aviv University encoded a toxin produced by bacteria into mRNA (messenger RNA) molecules and delivered these particles directly to cancer cells, causing the cells to produce the toxin – which eventually killed them with a success rate of 50%.

“Our idea was to deliver safe mRNA molecules encoded for a bacterial toxin directly to the cancer cells – inducing these cells to actually produce the toxic protein that would later kill them. It’s like placing a Trojan horse inside the cancer cell.” – Prof. Dan Peer

“It’s like placing a Trojan horse inside the cancer cell”

The groundbreaking study was led by PhD student Yasmin Granot-Matok and Prof. Dan Peer, a pioneer in the development of RNA therapeutics and Head of the Nanomedicine Laboratory at The Shmunis School of Biomedicine and Cancer Research, also serving as TAU’s VP R&D. The study’s results were published in Theranostics.

Prof. Peer explains: “Many bacteria secrete toxins. The most famous of these is probably the botulinum toxin injected in Botox treatments. Another classic treatment technique is chemotherapy, involving the delivery of small molecules through the bloodstream to effectively kill cancer cells. However, chemotherapy has a major downside: it is not selective, and also kills healthy cells. Our idea was to deliver safe mRNA molecules encoded for a bacterial toxin directly to the cancer cells – inducing these cells to actually produce the toxic protein that would later kill them. It’s like placing a Trojan horse inside the cancer cell.”

Prof. Dan Peer

Impressive Results

First, the research team encoded the genetic info of the toxic protein produced by bacteria of the pseudomonas family into mRNA molecules (resembling the procedure in which genetic info of COVID-19’s ‘spike’ protein was encoded into mRNA molecules to create the vaccine). The mRNA molecules were then packaged in lipid nanoparticles developed in Prof. Peer’s laboratory and coated with antibodies – to make sure that the instructions for producing the toxin would reach their target, the cancer cells. The particles were injected into the tumors of animal models with melanoma skin cancer. After a single injection, 44-60% of the cancer cells vanished.

“With a simple injection to the tumor bed, we can cause cancer cells to ‘commit suicide’, without damaging healthy cells. Moreover, cancer cells cannot develop resistance to our technology as often happens with chemotherapy – because we can always use a different natural toxin.” – Prof. Dan Peer

“In our study, the cancer cell produced the toxic protein that eventually killed it,” says Prof. Peer. “We used pseudomonas bacteria and the melanoma cancer, but this was only a matter of convenience. Many anaerobic bacteria, especially those that live in the ground, secrete toxins, and most of these toxins can probably be used with our method. This is our ‘recipe’, and we know how to deliver it directly to the target cells with our nanoparticles. When the cancer cell reads the ‘recipe’ at the other end it starts to produce the toxin as if it were the bacteria itself and this self-produced toxin eventually kills it. Thus, with a simple injection to the tumor bed, we can cause cancer cells to ‘commit suicide’, without damaging healthy cells. Moreover, cancer cells cannot develop resistance to our technology as often happens with chemotherapy – because we can always use a different natural toxin.”

Other contributors to the study included: Dr. Assaf Ezra, Dr. Srinivas Ramishetti, Dr. Preeti Sharma Dr. Gonna Somu Naidu and Prof. Itai Benhar, Head of the Antibody Engineering Lab at the Shmunis School of Biomedicine and Cancer Research at TAU. The study was funded by the Shmunis Family Foundation for Biomedicine and Cancer Research.

Metabolomics – A New Frontier in Preventive Medicine

Written by AUFTAU on 13 July 2023. Posted in Newsroom.

Tel Aviv University’s new Metabolite Medicine Division at the BLAVATNIK Center for Drug Discovery poised to revolutionize the field.

Even the simplest blood tests of today – which monitor about 20 substances in our body – have powerful predictive and diagnostic power. For example, high cholesterol suggests possible heart trouble, and abnormal glucose could indicate pre-diabetes.

Now imagine that routine and low-cost bloodwork could check for thousands of compounds all at once, as well as calculate the balance between them. Such a real-time status check would provide doctors with unparalleled knowledge for diagnosing patients and creating personalized profiles for the most effective treatment of disease.

“Metabolomics is poised to revolutionize the field of preventive medicine. It holds tremendous potential (…) not only for detecting diseases but also for enabling individuals to proactively monitor their overall physiological well-being even before the onset of illness.” – Prof. Ehud Gazit

The Super Blood Test

We are entering such an era at TAU’s new Metabolite Medicine Division at the BLAVATNIK CENTER for Drug Discovery. This suite of labs is the most advanced at an Israeli university for the emerging science of metabolomics – the study of small molecules called metabolites that our bodies produce every second of our lives as part of ongoing cell processes. Sometimes, all that is required is to identify the one metabolite culprit that is throwing the body off balance.

“Metabolomics is poised to revolutionize the field of preventive medicine. It holds tremendous potential as a cornerstone and indispensable tool, not only for detecting diseases but also for enabling individuals to proactively monitor their overall physiological well-being even before the onset of illness,” explains Prof. Ehud Gazit, the Founding Director of the Metabolomic Medicine division.

“Unlike genetics, which cannot be easily altered, the composition of metabolites provides a valuable reflection of the body’s physiological state, making it possible to optimize towards an ideal state through dietary interventions, physical activity, and lifestyle modifications,” he says.

“The establishment of the Metabolite Medicine division at the BLAVATNIK CENTER for Drug Discovery is highly important for the entire biomed framework of Tel Aviv University.” – Dr. Ludmila Bozhansky

Driving Real-Life Implementation

Using state-of-the-art equipment, scientists will be able to identify specific metabolic signatures in laboratory and patient cell culture samples, learn about their mechanisms of action, and develop AI-aided data analysis tools. The ultimate aim of the Metabolite Division is to connect promising university discoveries with Israeli hospitals for clinical samples and testing, and with the pharma industry for creating or repurposing drugs.

“The establishment of the Metabolite Medicine division at the BLAVATNIK CENTER for Drug Discovery is highly important for the entire biomed framework of Tel Aviv University,” says Dr. Ludmila Buzhansky, the Managing Director of the BLAVATNIk Center for Drug Discovery. “By leveraging the capabilities of metabolomics and benefiting from the exceptional expertise now available at TAU in this field, our researchers develop interdisciplinary collaborations that drive innovation and knowledge dissemination across diverse domains within the university community and beyond.”

Source: TAU Review

Older Bats do Suffer from Age-related Hearing Loss

Written by AUFTAU on 13 July 2023. Posted in Newsroom.

A new study from Tel Aviv University disproves the prevailing scientific assumption that bats are immune to age-related hearing loss. This assumption led researchers to mistakenly believe that because hearing is so critical to the bats’ echolocation system, they preserve a good hearing ability, enabling orientation even at an advanced age.

“Turn left at the next tree! Hey, did you catch that??”

In the present study the researchers found that the bats’ sense of hearing does in fact deteriorate with age, but at a relatively slow rate – compared to humans and other mammals. Since they live in very noisy colonies, where more rapid hearing loss might have been expected, the researchers hypothesize that the bats may have developed special adaptations that slow down the process.

The study was led by PhD student Yifat Tarnovsky from the laboratory of neuro-ecologist Prof. Yossi Yovel of the School of Zoology at The George S. Wise Faculty of Life Sciences, Head of TAU’s Sagol School of Neuroscience, in collaboration with Prof. Karen Avraham, Dean of TAU’s Faculty of Medicine, Dr. Shahar Taiber from her lab and Prof. Jerry Wilkinson from the University of Maryland. The paper was published in Life Science Alliance.

Prof. Yovel explains that the ability to discern high frequencies is critical for the survival of bats, which rely on it to orient themselves in their surroundings. However, to date no study has systematically examined the effects of aging on hearing in bats.

The researchers used DNA methylation accumulation to assess the age of 47 wild Egyptian fruit bats (Rousettus aegyptiacus), and then tested their hearing by monitoring auditory brainstem responses to sounds of varying frequency and intensity. The recordings clearly indicated age-related hearing loss, and just like in humans, this deterioration was more marked in the higher frequencies. The rate of deterioration was found to be similar to hearing loss observed in aging humans.

Prof. Yossi Yovel with two winged friends

Additional tests showed that like in humans, hearing loss in bats is related to the structure and function of the cochlea, alongside slower processing by the auditory nerve. Tarnovsky explains: “In humans, this last symptom can affect speech comprehension. In older bats it can be detrimental to echolocation. The Egyptian fruit bats we studied rely on echolocation to perform various tasks, but whenever possible they also rely substantially on eyesight. Therefore, our tests should be replicated in bats with poor eyesight, that rely almost exclusively on echolocation to orient themselves.”

New Discoveries About the Process of Hearing Loss

The researchers assume that one cause of hearing loss in Egyptian fruit bats could be cumulative exposure to high noise levels in their environment. Like many other bat species, Egyptian fruit bats live in large colonies and use loud and frequent social vocalizations to communicate. By placing several microphones inside the fruit bats’ cave, Tarnovsky and her colleagues discovered that the bats are frequently exposed to a sound intensity of over 100 dB, equal to that of a motorcycle or power saw. Surprisingly, the loudest noise was found in low frequencies, while the tests indicated that hearing loss occurs mostly in high frequencies.

“The relatively slow rate of age-related hearing loss (similar to the rate in humans) despite lifelong exposure to very high noise levels may indicate that bats have developed special adaptations for coping with their noisy surroundings,” says Prof. Yovel. The researchers hope that understanding these adaptations can provide new insights about the mechanisms of age-related hearing loss in humans.

Operation Guardian of the Walls: Women, Young People and Residents of the South Paid the Heaviest Price

Written by AUFTAU on 12 July 2023. Posted in Newsroom.

During Operation Guardian of the Walls, which took place in May 2021, researchers from Tel Aviv University carried out a groundbreaking study by equipping Israelis with smartwatches and a dedicated mobile application. The study aimed to examine the impact of the operation on the well-being of citizens by monitoring various objective and subjective indicators. The findings revealed that residents of Israel’s southern region suffered significantly more than the rest of the population.

Assessing Impacts, as well as Resilience

The innovative study was conducted by a team of researchers from Tel Aviv University: Prof. Erez Shmueli, Prof. Dan Yamin, and Ph.D. students Merav Mofaz and Matan Yechezkel of The Iby and Aladar Fleischman Faculty of Engineering; Prof. Noga Kronfeld-Schor of The George S. Wise Faculty of Life Sciences; and Prof. Haim Einat of the Academic College of Tel Aviv-Yafo. The findings of the groundbreaking study were published in the journal Communication Medicine from the Nature group.

According to Prof. Erez Shmueli, the study was part of a broader initiative called PerMed (Personalized Medicine), aimed at early diagnosis of infectious diseases like COVID-19. However, the timing of Operation Guardian of the Walls presented a unique opportunity to examine the physiological and mental changes experienced by civilians during wartime.

By May 2021, the researchers had enrolled 954 Israelis in the experiment, equipping them with smartwatches to assess the impact of the war on the home front. The data collected from the smartwatches and participants’ reports through the app revealed a significant deterioration in various metrics during the war compared to normal circumstances. Notably, after the war ended, all indicators returned to their previous levels on average, showcasing the mental resilience of Israelis. Nevertheless, the researchers observed notable differences among Israeli citizens: with residents of the southern areas (near Gaza), exposed to frequent and dangerous rocket attacks, enduring more significant mental and physiological effects compared to those in the central regions. Furthermore, central region residents suffered more than those in the north.

“In future research, it is crucial to identify individuals who experienced significant adversity during the war and did not fully recover following its conclusion. We believe that providing prompt and targeted support to these individuals may prevent the development of post-traumatic stress disorder (PTSD).” – Prof. Erez Shmueli

The findings highlighted several key differences among the citizens. For example, residents of the southern areas spent more time (6.2 hours) looking at their screens compared to central region residents (5.3 hours), and central region residents spent more screen time than those in the north (5 hours). Similar patterns emerged in other metrics, such as mood (3.24 in the south versus 3.45 in the center and 3.75 in the north, on a scale of 1 to 5), stress (2.8 in the south versus 2.6 in the center and 2.3 in the north, on a scale of 1 to 5), physical activity (20 minutes in the south compared to about 34 minutes in the center and in the north), sleep duration (6.1 hours in the south compared to 6.2 hours in the center and 6.5 hours in the north) and quality of sleep (2.9 in the south compared to 3.3 in the center and 3.5 in the north, on a scale of 1 to 5). Women and young people experienced more deviation from their normal patterns during the conflict compared to men and adults.

Since Operation Guardian of the Walls, there have been subsequent rounds of fighting between Israel and factions in Gaza, as well as Russia’s invasion of Ukraine. Prof. Shmueli believes that wearable technology holds immense potential in monitoring the consequences of such conflicts and providing aid to populations in need: “In the past, wars were fought at the borders,” says Prof. Shmueli. “Today, they are fought deep within the country. Therefore, monitoring the resilience of citizens is crucial, both as groups and as individuals. The state needs to know what happens to its citizens during war, as well as provide special support to groups that are more prone to harm. In future research, it is crucial to identify individuals who experienced significant adversity during the war and did not fully recover following its conclusion. We believe that providing prompt and targeted support to these individuals may prevent the development of post-traumatic stress disorder (PTSD).”

Due to Climate Change, More Animals will Become Extinct Outside of Nature Reserves than Within Them

Written by AUFTAU on 12 July 2023. Posted in Newsroom.

A new international study has found that amphibians and reptiles inhabiting the world’s nature reserves, or Protected Areas (PAs), will be better protected against climate change than species found outside of these areas, but are still likely to be harmed.

The research findings provide evidence, on a global scale, of the crucial role Protected Areas play in conserving amphibian and reptile biodiversity under human-induced climate change scenarios. The study reveals that more animals will become extinct because of climate change outside of Protected Areas than inside them — in the world in general and on most individual continents.

Protected Areas as Refuges

Prof. Shai Meiri of Tel Aviv University’s School of Zoology, The George S. Wise Faculty of Life Sciences and The Steinhardt Museum of Natural History took part in the study, in collaboration with leading researchers from 19 countries. The study was published in the prestigious journal Nature Communications.

“Approximately 91% of the amphibian and reptile species we examined are protected, to some degree, in Protected Areas, and this proportion will remain unchanged under future climate change.” – Prof. Shai Meiri

The purpose of the study was to evaluate the effectiveness of existing Protected Areas in protecting the amphibians and reptiles living within them under future climate scenarios, as well as to identify conservation gaps in order to outline a road map for the development of conservation actions based on the current global network of Protected Areas.

“In this study, we collected distribution data for more than 14,000 species of amphibians and reptiles — about 70% of the known species — to perform a global assessment of the conservation effectiveness of Protected Areas in an era of climate change, using species distribution models,” explains Prof. Meiri. “Our analyses revealed that approximately 91% of the amphibian and reptile species we examined are protected, to some degree, in Protected Areas, and that this proportion will remain unchanged under future climate change. Furthermore, species protected in Protected Areas will lose smaller portions of their distribution ranges inside the nature reserve than outside of them. Therefore, the proportion of species within reserves is expected to increase.”

Relative Optimism

However, Prof. Meiri points out, “We predict that more than 300 of the amphibian species and 500 of the reptile species we studied will become extinct due to climate change in the coming decades, and probably also hundreds of species for which we did not have sufficient data to model. Our research highlights the importance of Protected Areas in providing refuge for amphibians and reptiles in face of climate change and points out areas where there are not enough nature reserves that can better preserve biodiversity around the world.”

“Despite the relative optimism emerging from the new research, the models still predict extremely high rates of loss of species and habitats due to climate change. Protected Areas do indeed protect the animals living within them, but nothing is foolproof.” – Prof. Shai Meiri

He adds: “We compiled a comprehensive global database with more than 3.5 million observation records spanning 5,403 amphibian species and 8,993 reptile species from online databases, fieldwork data, museum collections, and published references. For all species in our database, we predicted habitat availability according to current (1960–1990) climate data and future scenarios (for the years 2060–2080) at a high spatial resolution (1 km × 1 km) using species distribution models. Then, we evaluated the effectiveness of Protected Areas in conserving amphibians and reptiles by calculating the coverage of their distribution range inside and outside of Protected Areas, as well as the proportion of species for whom a significant portion of their distribution range (for example, 15% or 30%) is protected in PAs under current and future climate conditions (assuming that the future use of the land remains unchanged over the years — that is, that there will be no conversion of nature reserves into agricultural, industrial, or urban areas.)”

Prof. Meiri concludes: “Our evidence shows that the current global network of Protected Areas already plays an important role in preserving the global biodiversity of amphibians and reptiles, and will continue to do so under the expected future climate. However, many species do not live in the existing Protected Areas. These include, for example, many amphibians and reptiles in Mexico, Jamaica, the Andes, West Africa, South Africa, the southern and northern coast of Turkey, Yemen and other places. Moreover, in our study we could create a model for only about two-thirds of reptile and amphibian species. Good models can’t be created for the rarest species, which are known to be more vulnerable to extinction and less protected in Protected Areas. At the same time, it is important to remember that despite the relative optimism emerging from the new research, the models still predict extremely high rates of loss of species and habitats due to climate change. Protected Areas do indeed protect the animals living within them, but nothing is foolproof.”

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