Tag: Medicine & Health

Are We Getting to the Root of Cancer?

Groundbreaking discovery that plant roots grow in a spiral motion inspires search for similar motion in cancer cells.

In an interdisciplinary research project carried out at Tel Aviv University, researchers from the School of Plant Sciences affiliated with The George S. Wise Faculty of Life Sciences collaborated with their colleagues from the Sackler Faculty of Medicine in order to study the course of plant root growth. Aided by a computational model constructed by cancer researchers studying cancer cells, adapted for use with plant root cells, they were able to demonstrate, for the first time in the world, and at the resolution of a single cell, that the root grows with a screwing motion – just like a drill penetrating a wall. In the wake of this study, the cancer researchers conjecture that cancer cells, too, are assisted by a spiral motion in order to penetrate healthy tissue in the environment of the tumor, or to create metastases in various organs of the body. The research was led by Prof. Eilon Shani from the School of Plant Sciences and Food Security and Prof. Ilan Tsarfaty from the Department of Clinical Microbiology and Immunology at Tel Aviv University, and was conducted in collaboration with researchers from the USA, Austria and China. The article was published in March 2021 in the acclaimed journal Nature Communications.

Significant Advance in Plant Research – and in the War on Cancer?

The researchers in Prof. Shani’s group, led by Dr. Yangjie Hu, used as a model the plant known as Arabidopsis. They marked the nuclei of the root cells with a fluorescent protein and observed the growing process and movement of the cells at the root tip through a powerful microscope – approximately 1000 cells in each movie. Furthermore, in order to examine what causes and controls the movement, they focused on a known hormone named auxin, which regulates growth in plants. They built a genetic system that enables activation of auxin production (like a switch) in a number of selected cells-types, and then monitored the influence of the on/off mechanism, in four dimensions – the three spatial dimensions and the dimension of time. After each instance of auxin biosynthesis, each of the thousand cells was video recorded for a period of 6 to 24 hours, thus an enormous amount of data accumulated.

WATCH: The process of growth and movement of cells at the root tip using a microscope

For the next stage, the researchers were aided by the computational tools provided by Prof. Tsarfaty, which had been developed in his laboratory for the purpose of monitoring the development of cancerous growths. They used these tools to analyze the imaging data obtained in the study. Thus they were actually able, for the first time, to observe with their own eyes the corkscrew movement of the root, as well as to precisely quantify and chart some 30 root growth parameters relating to time and space – including acceleration, length, changes in cell structure, coordination between cells during the growth process and velocity – for each one of the thousand cells at the root tip. Using fluorescent reporters, the findings even allowed them to precisely assess the movement and the influence of the auxin on the root, and the way in which it controls the growth process. Prof. Shani: “The computational tools that were developed for cancer research have enabled us, for the first time, to precisely measure and quantify the kinetics of growth and to reveal the mechanisms that control it at the resolution of a single cell. By this they have significantly advanced plant research, an area of utmost importance for society – both from an environmental point of view and in terms of agriculture and feeding the population.” Prof. Tsarfaty adds: “This was a synergetic collaboration that benefited and enlightened both parties. In plants, processes take place much more rapidly, and therefore constitute an excellent model for us. In consequence of the findings provided by this plant study, we are presently examining the possibility of a similar screw-like motion in cancer cells and in metastases, in the course of their penetration into adjacent healthy tissues.”

Optical Technology Generates Immediate Melanoma Diagnosis

Expected to revolutionize the field of skin cancer diagnosis.

Melanoma is a life-threatening cancer, but its immediate diagnosis can save lives. An innovative optical technology that can distinguish between different types of cancer has now been developed in the laboratory of Professor Abraham Katzir, from the Raymond and Beverly Sackler Faculty of Exact Sciences at Tel Aviv University, which enables real time diagnosis of melanoma. Based on special optical fibers, the technology will enable every dermatologist to determine the character of a suspicious lesion automatically, and particularly if it is melanoma. Non-invasive, immediate, and automatic, this process may lead to a dramatic change in the field of diagnosing and treating skin cancer, and possibly other types of cancer as well. The technology has been tried successfully on about one hundred patients in a major hospital in Israel. The findings were published in the Journal Medical Physics.

Seeing Skin Cancer’s True Colors

When a suspicious lesion is found on the skin, during a routine examination, it is removed in a minor surgical procedure and sent to a laboratory for testing. A pathologist diagnoses the lesion and determines whether it is melanoma. In most cases where melanoma is discovered early, when it is still superficial and less than one-millimeter-thick and it is removed, the patient recovers. Late diagnosis, when the melanoma is more than one-millimeter-thick, significantly reduces the chances of recovery and is life-threatening. “The idea that guided us in developing the technology was that in the visible range, there are various substances, having various colors, which are not characteristic of each substance. On the other hand, in the infrared region, various substances have different ‘colors’ of a sort, depending on the chemical makeup of each substance,” says Professor Katzir. “Therefore, we figured that with the help of devices that can identify these ’colors’, healthy skin and each of the benign and malignant lesions would have different ’colors’, which would enable us to identify melanoma.” Professor Katzir’s research group developed special optical fibers that are transparent in the infrared. The group, in collaboration with physicists Professor Yosef Raichlin of Ariel University, Dr. Max Platkov of the Negev Nuclear Research Center, and Svetlana Bassov of Professor Katzir’s group, developed a system, based on these fibers, in accordance with the requirements of evaluating skin. The researchers connected one end of this type of fiber to a device that measures the ’colors’ in the infrared, and touched the other end lightly, for several seconds, to a lesion on a patient’s skin. The fiber made it possible to check the ’color’ of the lesion right away. Clinical trials were then carried out on suspicious lesions in about one hundred patients. With the help of the new system, physicists performed measurements of the ’color’ of each lesion, before it was removed and sent to a pathology laboratory. The researchers showed that all of the lesions that were determined by pathologists as being of a certain type, such as melanoma, had a characteristic ’color’ in the infrared. Each type of lesion had a different ’color’. “The technology gives us a kind of ‘fingerprint’, which makes it possible to diagnose the various lesions by measuring their characteristic ’colors’”, says Professor Katzir. “In this way, lesions can be diagnosed using a non-invasive optical method, and the physician and the patient receive the results automatically and immediately.  This is unlike the test that is routinely used, which involves surgery, and the pathological diagnosis takes a long time.” Following the success of the study, the researchers plan to confirm the evaluation method on hundreds of patients.  

Non-invasive, immediate, and automatic

In conclusion, Professor Katzir says: “Melanoma is a life-threatening cancer, so it is very important to diagnose it early on, when it is still superficial. The innovative system will enable every dermatologist to determine the character of a suspicious lesion automatically, and particularly if it is melanoma. This system has the potential to cause a dramatic change in the field of diagnosing and treating skin cancer, and perhaps other types of cancer as well. The challenge will be to make this technology, which is still expensive, something that will be used in every hospital or clinic.”

Gut Healing

TAU researchers identify proteins that cause intestinal disease.

Researchers from Tel Aviv University have created an artificial intelligence platform that can identify the specific proteins that allow bacteria to infect the intestines – a method that paves the way for the creation of smart drugs that will neutralize the proteins and prevent disease, without the use of antibiotics. Participating in the study, which was published in the prestigious journal Science, were Ph.D. student Naama Wagner and Prof. Tal Pupko, Head of The Shmunis School of Biomedicine and Cancer Research at the Faculty of Life Sciences and the new Center for Artificial Intelligence & Data Science at Tel Aviv University. The international partners in the study included researchers from Imperial College (led by Prof. Gad Frankel) and the Institute for Cancer Research in London, as well as from the Technical University and the National Center for Biotechnology in Madrid.

Swapping the Cannon for a Rifle

Intestinal diseases are caused by pathogenic bacteria that attach to our intestinal cells. Once attached, the bacteria use a kind of molecular syringe to inject intestinal cells with proteins called “effectors.” These effectors work together to take over healthy cells, like hackers that take over computer servers using a combination of lines of code. However, until now scientists have not known what protein combination it is that cracks the cell’s defense mechanisms. Now, the TAU researchers’ artificial intelligence platform has identified novel effectors in the bacteria, which have been experimentally tested and validated. Subsequently, laboratory experiments conducted in London successfully predicted the protein combinations that lead to the pathogenic bacteria taking over the intestines. “In this study, we focused on a bacterium that causes intestinal disease in mice, a relative of the E. coli bacteria that cause intestinal disease in humans, so as not to work directly with the human pathogen”, explains Ph.D. student Naama Wagner. “The artificial intelligence we created knows how to predict effectors in a variety of pathogenic bacteria, including bacteria that attack plants of economic importance. Our calculations were made possible by advanced machine-learning tools that use the genomic information of a large number of bacteria. Our partners in England proved experimentally that the learning was extremely accurate and that the effectors we identified are indeed the weapons used by the bacteria.” “Pathogenic bacteria are treated with antibiotics,” says Prof. Tal Pupko. “But antibiotics kill a large number of species of bacteria, in the hope that the pathogenic bacteria will also be destroyed. So antibiotics are not a rifle but a cannon. Moreover, the overuse of antibiotics leads to the development of antibiotic-resistant bacteria, a worldwide problem that is getting worse. Understanding the molecular foundation of the disease is a necessary step in the development of drugs that are smarter than antibiotics, which will not harm the bacterial population in the intestines at all. This time we discovered the effectors of gut bacteria that attack rodents, but this is just the beginning. We are already working on detecting effectors in other bacteria in an attempt to better understand how they carry out their mission in the target cells they are attacking.”

Could Your Smartphone Be Damaging Your Teeth?

Your FOMO may be compromising your physical and mental health.

Do you often find yourself checking your social media nonstop, so you won’t feel out of the loop? You may want to become more mindful of this habit – a new study from Tel Aviv University’s Maurice and Gabriela Goldschleger School of Dental Medicine shows that the excessive use of smartphones and social media can lead to sleep issues; drowsiness and fatigue during the day; teeth-grinding and pain in the mouth muscles and jaws. The study was conducted as part of Dr. Yitzhak Hochhauser’s dissertation and was led by Dr. Alona Amudi-Perlman, Dr. Pessia Friedman-Rubin, Prof. Ilana Eli, and Prof. Ephraim Winocur. It will be published in the journal Quintessence International. About 600 participants, including a group of secular people (smartphone users) and a group of ultra-Orthodox people (most of whom use a “kosher” phone without an Internet connection), were asked to address a number of aspects that typify overuse of the phone, including feelings of stress and tension throughout the day, a tendency to wake up at night, a need to be available to the cell phone, teeth-grinding and jaw pain.

More Screen Time = More Sufferings

The findings of the study show that 54% of secular smartphone users have a moderate to high incidence of night wakings, compared with only 20% among the ultra-Orthodox. In addition, half of the secular respondents (50%) feel a moderate to high level of stress due to the cell phone, compared to only 22% among the ultra-Orthodox. The disparities between the groups are also reflected in the question of how available they feel they need to be to their mobile devices – 45% of the secular respondents answered that they had a moderate to high need to be available to their phones, compared to only 20% in the ultra-Orthodox group. These gaps are even more marked when examining damage to the chewing muscles and jaw joints: 45% of the secular group reported teeth-grinding (24% during the day and 21% at night) and 29% of them claimed that they suffered pain in their jaw muscles, in comparison to only about 14% of the ultra-Orthodox who described these symptoms (13.5% reported teeth-grinding and 14% pain in the jaw muscles). Dr. Friedman-Rubin and Prof. Eli explain that “In today’s day and age people live with a sense of FOMO (fear of missing out) and so they want to stay constantly updated and know ‘what’s new’ every moment. This need naturally creates a growing dependence on cell phones, which leads to feelings of stress and anxiety – ‘someone might write something on social media and I’ll miss it and not be in the loop.’” Dr. Friedman-Rubin explains, “The current study has demonstrated a link between the excessive use of smartphones that enable surfing on social apps and a significant increase in night wakings (which lead to fatigue during the day), facial and jaw pain, tightness in the jaw during the day and teeth-grinding at night – physical symptoms that are often the result of stress and anxiety and which may even lead to physical injury such as dental erosion and joint damage. We are of course in favor of technological progress, but as with everything in life, the excessive use of smartphones can lead to negative symptoms, and it is important that the public be aware of the consequences it has on the body and mind.”

The Quest for A Lifesaving Cure

Innovative technology of BLAVATNIK CENTER for Drug Discovery may save boy suffering from rare neurological syndrome.

In December 2019, the BLAVATNIK CENTER for Drug Discovery at Tel Aviv University was presented with a challenge which demanded flexibility and thinking outside the box. Prof. Ehud Gazit, Founder and Academic Director of the BLAVATNIK CENTER for Drug Discovery at Tel Aviv University, received an email from Scott Reich, a very worried father. Scott’s son Eli, only eight months old at the time, had just been diagnosed with the ultra-rare FOXG1 syndrome, a neurological disorder that severely impacts brain development. With only about 700 known cases worldwide, predominantly children with severe disabilities, this devastating condition attracts little research and has no cure. Determined to save his son, Scott searched all over the world for experts who could develop a treatment for the rare syndrome. The advice and recommendations of leading scientists and health professionals led him to the BLAVATNIK CENTER at TAU in Israel, which specializes in the field of drug repurposing: repurposing FDA-approved medications and other safe substances to help people with rare diseases, all too often overlooked by the big pharmaceutical companies. Dr. Eddy Pichinuk, Head of the HTS and Biological Assays Unit at BLAVATNIK CENTER, whose team was already conducting research for several other families affected by rare diseases, willingly accepted the new challenge. Dr Pichinuk and his team quickly obtained a sample of Eli’s cells, which had been deposited in a biobank for rare disease biosamples, and established a personalized drug-screening platform to test these cells against known, safe, FDA-approved molecules that could be repurposed. Essentially, they were looking for any drug (originally developed for some other purpose) that would increase the amount of FOXG1 protein in Eli’s brain, making up for the damaging deficiency caused by the mutation. The researchers were well aware that this might be Eli’s only hope for a more normal life: once a safe and effective drug is identified, it can be repurposed to offer Eli and others like him compassionate treatment. “Our screening platform is based on a luminescent protein, expressed in fireflies, that replaces the faulty protein in Eli’s cells,” explains Eddy. “We are screening a library of about 7,000 FDA-approved substances, initially developed to treat a range of diseases, such as cancer, psychiatric disorders, or various inflammatory syndromes. By testing each drug’s interaction with the marked protein in Eli’s cells, we have so far discovered several potentially helpful drug candidates. As we begin to see the light at the end of the tunnel, we continue to search for additional drugs.” In the next stage, the researchers will use advanced methods of genetic engineering to transform skin samples from Eli and his parents into stem cells and then into neurons. Ultimately, they will test the effect of the chosen drugs on Eli’s neurons. Determined and optimistic, they aim to restore more normalized brain development.

Thinking Outside the Box

Dr. Avi Raveh, the BLAVATNIK CENTER’s Chief Scientific Officer, explains that the Center offers a unique research approach, applying personalized medicine methodology to rare diseases. “We respond to requests from families all over the world, often at the last moment before they lose hope. Unlike large research institutions, we resemble a small and dynamic startup, eliminating or speeding up any bureaucracy and getting right down to the crux of the challenge. In Eli Reich’s case, with the time window for brain development closing fast, this flexibility is crucial. I truly hope that we can help him.” “Coming to Israel and working with the BLAVATNIK CENTER has been a good experience so far,” says Scott. Thanks to the Israeli spirit of collaboration, researchers at the Weizmann Institute of Science and Ben-Gurion University of the Negev have also been recruited to join the mission of saving Eli. He remains hopeful: “When we heard the devastating diagnosis, I said to my wife Ilissa: ‘We have to go to Israel. In Israel, we’ll find the know-how, experience and out-of-the-box thinking that we need.’ Reaching out through the American Jewish community and our Israeli friends, we got in touch with the BLAVATNIK CENTER for Drug Discovery, and immediately felt at home. The team is very creative, they work fast and are sincerely dedicated to finding a treatment for FOXG1 syndrome – they’re not just looking to publish a paper in a scientific journal. For us, this genuine commitment is extremely important. The BLAVATNIK CENTER team is doing everything they can so that Eli and others with FOXG1 Syndrome may live and hopefully enjoy more productive lives.” For more information about FOXG1 and Eli Reich, please visit BELIEVE IN A CURE Featured image: The Reich Familiy

A Healthier Alternative to Antibiotics

New study proves biological treatment can be a suitable alternative to antibiotics.

In a groundbreaking new study led by Dr. Natalia Freund and doctoral candidate Avia Watson at the TAU Sackler Faculty of Medicine, researchers were able to develop a “biological antibiotic” and demonstrates that human antibodies can offer an alternative to the traditional chemical antibiotics. The study was conducted in collaboration with laboratories in the United States and China and published in the prestigious scientific journal Nature Communications.

During the past century, antibiotics have served as the main treatment against bacteria, being both efficient and cheap. Antibiotics are chemical agents, designed to block and destroy specific cells, such as microbial cells. However, since some biological mechanisms are common to both human and microbial cells, the range of antibiotics that can safely be used without harming the patient is limited. For example, cell wall components of many strains of microbes are common to human cells; therefore, any damage caused to the microbial cell walls can lead to extensive damage to body systems. Furthermore, in recent years the number of microbial strains that are resistant to existing antibiotics has grown, which presents new challenges of defending the body from microbes in the post-antibiotic era.

For these reasons, Dr. Natalia Freund and her laboratory team have spent the recent years searching for a biological alternative to known antibiotics. Dr. Freund explains, “Advances in biological medicine have enabled us to rout the germs in new ways that are not based solely on antibiotics, allowing for a solution to the challenge posed by resistant germs. Our study is an initial proof of the concept of employing monoclonal antibodies (derived from single cells) as an effective therapy for combating bacterial pathogens”. Antibodies are proteins that are produced naturally by our immune response following infection or a vaccine. They harbor many advantages such as specificity, stability and safety. This is why antibodies are today in widespread use in the clinic for treatment of cancer, autoimmune diseases and viral infections such as COVID-19.

Tuberculosis as Test Case

The research team chose Tuberculosis, which is caused by infection of the bacilli Mycobacterium tuberculosis, as a test case and were able, for the first time ever, to create an effective treatment based on anti-bacterial antibodies that developed naturally during infection (the antibodies were extracted from a patient who had been infected, and has since recovered, from tuberculosis). Another reason for the choice of tuberculosis is that although the vaccine against tuberculosis was developed 100 years ago (and is based on the attenuated bacillus bovis (BCG) strain), it is not effective for adults and does not prevent infection. In addition, in recent years, more and more strains of disease have developed that are resistant to the only treatment currently available: treatment with antibiotics. Since tuberculosis bacteria are highly contagious and are transmitted through the air and damaging to the lungs, the spread of untreated resistant strains of tuberculosis constitutes a real hazard. Today, about a quarter of the world’s population is infected with tuberculosis, with the rates of drug-resistant strains peaking   as high as 40% in some countries. In Israel, there are about 200 active tuberculosis cases every year.

 

Dr. Natalia Freund and her research team

Future Targets: Pneumonia and Staphylococcal Infections

Due to the size and complexity of the tuberculosis bacillus, previous efforts to isolate monoclonal antibodies against it have been futile. The researchers in Dr. Freund’s laboratory have succeeded in isolating two types of antibodies which contributed to a 50% reduction of the bacterial levels in mice relative to other mice that were not treated with antibodies. These antibodies have been found to be effective against three different strains of the tuberculosis bacterium and are expected to be effective also against additional strains that have not yet been investigated, including strains that are resistant to antibiotics

Following the success of the study, Dr. Freund’s laboratory is currently exploring the possibility of extending the “biological” substitute for antibiotics to include other diseases. “The demonstrated case for this study will enable us to expand on our future work to include diseases such as pneumonia and staphylococcal infections,” says Dr. Freund.

Cancer Breakthrough: Cells’ Uniqueness is Also Weakness

TAU research proves connection for first time, can be base for cancer drugs.

What makes cancer cells different from ordinary cells in our bodies? Can these differences be used to strike at them and paralyze their activity? This basic question has bothered cancer researchers since the mid-19th century. The search for unique characteristics of cancer cells is a building block of modern cancer research. A new study led by researchers from Tel Aviv University shows, for the first time, how an abnormal number of chromosomes (aneuploidy) — a unique characteristic of cancer cells that researchers have known about for decades — could become a weak point for these cells. The study could lead, in the future, to the development of drugs that will use this vulnerability to eliminate the cancer cells.

The study, which was published in Nature, was conducted in the laboratory of Dr. Uri Ben-David of the Sackler Faculty of Medicine at Tel Aviv University, in collaboration with six laboratories from four other countries (the United States, Germany, the Netherlands, and Italy).

Aneuploidy is a hallmark of cancer. While normal human cells contain two sets of 23 chromosomes each — one from the father and one from the mother — aneuploid cells have a different number of chromosomes. When aneuploidy appears in cancer cells, not only do the cells “tolerate” it, but it can even advance the progression of the disease. The relationship between aneuploidy and cancer was discovered over a century ago, long before it was known that cancer was a genetic disease (and even before the discovery of DNA as hereditary material).

According to Dr. Ben-David, aneuploidy is actually the most common genetic change in cancer. Approximately 90% of solid tumors, such as breast cancer and colon cancer, and 75% of blood cancers, are aneuploid. However, our understanding of the manner in which aneuploidy contributes to the development and spread of cancer is limited.

In the study, the researchers used advanced bioinformatic methods to quantify aneuploidy in approximately 1,000 cancer cell cultures. Then, they compared the genetic dependency and drug sensitivity of cells with a high level of aneuploidy to those of cells with a low level of aneuploidy. They found that aneuploid cancer cells demonstrate increased sensitivity to inhibition of the mitotic checkpoint – a cellular checkpoint that ensures the proper separation of chromosomes during cell division.

They also discovered the molecular basis for the increased sensitivity of aneuploid cancer cells. Using genomic and microscopic methods, the researchers tracked the separation of chromosomes in cells that had been treated with a substance that is known to inhibit the mitotic checkpoint. They found that when the mitotic checkpoint is perturbed in cells with the proper number of chromosomes, cell division stops. As a result, the chromosomes in the cells separate successfully, and relatively few chromosomal problems are created. But when this mechanism is perturbed in aneuploid cells, cell division continues, resulting in the creation of many chromosomal changes that compromise the cells’ ability to divide, and even cause their death.

The study has important implications for the drug discovery process in personalized cancer medicine. Drugs that delay the separation of chromosomes are undergoing clinical trials, but it is not known which patients will respond to them and which will not. The results of this study suggest that it will be possible to use aneuploidy as a biological marker, based on possibility to find the patients who will respond better to these drugs. To put it another way, it will be possible to adapt drugs that are already in clinical trials for use against tumors with specific genetic characteristics.

In addition, the researchers propose focusing the development of new drugs on specific components of the mechanism of chromosomal separation, which were identified as especially critical to aneuploid cancer cells. The mitotic checkpoint is made up of several proteins. The study shows that the aneuploid cells’ sensitivity to inhibition of the various proteins is not identical, and that some proteins are more essential to cancer cells than others. Therefore, the study provides motivation for developing specific drugs against additional proteins in the mitotic checkpoint.

“It should be emphasized that the study was done on cells in culture and not on actual tumors, and in order to translate it to treatment of cancer patients, many more follow-up studies must be conducted. If they hold true in patients, however, our findings would have a number of important medical implications,” Dr. Ben-David says.

The study was conducted in collaboration with laboratories from five countries: Dr. Zuzana Storchová, (Technische Universität Kaiserslautern, Germany), Dr. Jason Stumpff (University of Vermont, USA), Dr. Stefano Santaguida (University of Milano, Italy), Dr. Floris Foijer (University of Groningen, the Netherlands), and Dr. Todd Golub (The Broad Institute of MIT and Harvard, USA).

TAU Scientists Develop Innovative Therapy to Prevent Deafness

The treatment is inserted into the ear, prevents hearing loss caused by a genetic mutation.

A new study at Tel Aviv University presents an innovative treatment for deafness, based on the delivery of genetic material into the cells of the inner ear. The genetic material ‘replaces’ the genetic defect and enables the cell to continue functioning normally.

The scientists were able to prevent the gradual deterioration of hearing in mice with a genetic mutation for deafness. They maintain that this novel therapy could lead to a breakthrough in treating children born with various mutations that eventually cause deafness.

The study was led by Prof. Karen Avraham and Shahar Taiber, a student in the combined MD-PhD track, from the Department of Human Molecular Genetics and Biochemistry at the Sackler Faculty of Medicine, and the Sagol School of Neuroscience, and Prof. Jeffrey Holt from Boston Children’s Hospital and Harvard Medical School. Additional contributors included Prof. David Sprinzak from the School of Neurobiology, Biochemistry and Biophysics at the George S. Wise Faculty of Life Sciences at Tel Aviv University. The paper was published in EMBO Molecular Medicine.

Deafness is the most common sensory disability worldwide. According to the World Health Organization there are about half a billion people with hearing loss around the world today, and this figure is expected to double in the coming decades. One in every 200 children is born with a hearing impairment, and one in every 1,000 is born deaf. In about half of these cases, deafness is caused by a genetic mutation. There are currently about 100 different genes associated with hereditary deafness. 

Prof. Avraham: “In this study we focused on genetic deafness caused by a mutation in the gene SYNE4 – a rare deafness discovered by our lab several years ago in two Israeli families, and since then identified in Turkey and the UK as well. Children inheriting the defective gene from both parents are born with normal hearing, but gradually lose their hearing during childhood. This happens because the mutation causes mislocalization of cell nuclei in the hair cells inside the cochlea of the inner ear, which serve as soundwave receptors and are thus essential for hearing. This defect leads to the degeneration and eventual death of hair cells.” 

Shahar Taiber: “We implemented an innovative gene therapy technology: we created a harmless synthetic virus and used it to deliver genetic material – a normal version of the gene that is defective in both the mouse model and the affected human families. We injected the virus into the inner ear of the mice, so that it entered the hair cells and released its genetic payload. By so, we repaired the defect in the hair cells, and enabled them to mature and function normally.”

The treatment was administered soon after birth and the mice’s hearing was then monitored using both physiological and behavioral tests. Prof. Holt: “The findings are most promising: Treated mice developed normal hearing, with sensitivity almost identical to that of healthy mice who do not have the mutation”. Following the successful study, the scientists are currently developing similar therapies for other mutations that cause deafness.

Prof. Wade Chien, MD, from the NIDCD/NIH Inner Ear Gene Therapy Program and Johns Hopkins School of Medicine, who was not involved in the study, illuminates its significance: This is an important study that shows that inner ear gene therapy can be effectively applied to a mouse model of SYNE4 deafness to rescue hearing. The magnitude of hearing recovery is impressive. This study is a part of a growing body of literature showing that gene therapy can be successfully applied to mouse models of hereditary hearing loss, and it illustrates the enormous potential of gene therapy as a treatment for deafness.

The study was supported by the BSF – US-Israel Binational Science Foundation, the NIH – National Institutes of Health, the ERC – European Research Council, and the Israel Precision Medicine Partnership Program of the Israel Science Foundation.

Two TAU Professors Win 2020 Nature Mentoring Award

Prof. Neta Erez and Prof. Tal Pupko, nominated by students, are building the future generation of scientists.

Two scientists from Tel Aviv University – Professor Neta Erez, head of the Department of Pathology at Tel Aviv University’s Sackler School of Medicine, and Professor Tal Pupko, head of the Shmunis School of Biomedicine and Cancer Research at the Life Sciences Faculty, have won the 2020 Nature Research Awards for Mentoring in Science, given by the Springer Nature Group, which is the home of the leading journal Nature.

The prestigious award (which is given in a different country each year), was given in Israel this year, with Tel Aviv University sweeping all the honors for mid-career mentoring. The award is given to scientists who excel in mentoring research students in their laboratories, thus contributing to the development of the future of science — in Israel in particular and in the world in general. Both winners will share the $10,000 prize. They said that the prize was especially moving for them because the ones who had nominated them for it were the very ones whom they mentored — the students and graduates of their laboratories.

Professor Erez, who established a laboratory ten years ago for researching metastasis of breast cancer and melanoma, and who has mentored 16 doctoral candidates and five master’s degree students so far, said, “For me, mentoring is a central part of my identity as a scientist. When a doctoral candidate comes to me, I tell them: ‘You are starting off as my student, and I want you to end up as my peer.’ For that reason, my role as a mentor is not only to accompany the research. My role is to teach my students to think and do research like scientists, and to find their own way in science and in life in general.  I am very proud of their accomplishments. Quite a few graduates of the laboratory have been awarded prizes and grants. As of now, four of the students have completed their medical studies and are planning to combine medicine and research. One is a research fellow and a lab manager in an academic setting, another is doing post-doctoral work in the United States, and four others are working as scientists in the biotech industry. In addition, I serve as a mentor for two young researchers who recently established their own laboratories.” 

Professor Pupko, who established a laboratory 17 years ago that deals with molecular evolution and bioinformatics, has mentored 18 doctoral candidates so far. “The members of the academic staff are evaluated based on a variety of parameters: research grants, publications and teaching. Another index, which I feel does not receive enough emphasis, is the success of a staff member’s laboratory graduates — the young scientists whom he taught, mentored, and ‘raised.'” I invest a great deal of thought and effort in my students in order to support, encourage, advise, and nurture them. All 12 doctoral candidates who completed their degree in my laboratory have gone on to do post-doctoral work.  Four of them are staff members in academia (including three at Tel Aviv University) — a particularly high number for an academic research laboratory. Other graduates of my laboratory hold high-ranking positions in the hi-tech and bio-tech industries. As I see it, a student who excels is better than another three scientific papers. My aim is to raise up generations of researchers in Israel. I see that as my mission.”

The prize committee, which included Professor Karen Avraham of the Faculty of Medicine at Tel Aviv University, announced that it had chosen the two recipients because “it was impressed with their contagious enthusiasm of former students,” who had nominated them for the award. The committee also praised Professor Pupko for his inclusive approach and encouragement of a healthy work-life balance alongside professional excellence, and Professor Erez for her work to advance women in science and for projects that bring her influence as a mentor to wider circles, including ones outside her laboratory.

Lack of Teacher Support during Pandemic Causes Acute Emotional Harm

TAU study provides insights into preventing burnout among educators.

A new Tel Aviv University study led by Dr. Shahar Lev-Ari, Head of the Department of Health Promotion at TAU’s Sackler Faculty of Medicine study examined the psychological resilience of teachers before and during the coronavirus pandemic. The researchers monitored two groups of teachers in central Israel through the greater part of a single schoolyear. The first group received professional support (via the IBSR method), which included workshops and tools for promoting personal health, relieving stress and strengthening mental resilience, while the control group continued to work as usual in class and then in online sessions, without this support.

The study took place from November 2019 to May 2020, with participants teaching first in the classroom and then, starting with Israel’s first lockdown in March 2020, exclusively online.  In a questionnaire handed out before the beginning of the first study, teachers reported high levels of burnout as a result of large classes, schedule overload and lack of satisfactory resources.

The research team’s findings indicate significant gaps: On one hand, teachers in the group that received psychological support reported a significant rise in mental resilience and satisfaction with their lives in general, which continued after the onset of the pandemic. During the pandemic, they reported a better ability to cope and an improvement in their emotional welfare, including more positive emotions, a stronger sense of connection to their work and purpose, and greater drive and ambition. They also reported enhanced ability to relate to and listen to their students and to maximize their professional capabilities in class.

On the other hand, the control group, which did not receive support, reported that feelings of frustration and burnout, exhaustion and low self-fulfillment intensified, both during the academic year and the pandemic, when online teaching was required. The teachers in this group reported feeling “total exhaustion” at the end of the day, and sometimes also frustration and a lack of motivation to start a new workday.

The study was conducted by: Dr. Shahar Lev-Ari, research student Tsafnat Zadok from the Department of Health Promotion, Dr. Ronit Jakobovich, Etti Dvash and Keren Zafrani. The workshops were led by Keren Zafrani, a professional teacher and IBSR expert.

Dr. Shahar Lev-Ari: “The pandemic posed new challenges that naturally generated feelings of stress and anxiety among teachers. In addition to the quick transition to online teaching, teachers had to cope with uncertainty and constantly changing regulations, as well as personal fear of contracting the virus.

Our study clearly shows that when mental resilience is prioritized and tools for overcoming their stress and anxiety are provided, a rise in motivation and emotional welfare is observed. Accordingly, we observed that when teachers did not receive the required guidance and mental skills, their negative feelings, which were also reported in normal times, grew and intensified. This was especially acute during the pandemic – reaching levels of extreme exhaustion and a lack of motivation to start the workday.”

Dr. Lev-Ari adds: “Many studies have shown that teachers’ burnout is a covert cause of heart disease and sleep disorders, and also has a negative impact on the immune system. Burnout is also the reason why many teachers leave the profession after just a few years of teaching. I hope that following the significant improvement exhibited in this study, the education system will implement intervention programs based on the model described above or similar models. This is especially critical during the pandemic, when teachers face new pressures that intensify feelings of stress, anxiety and frustration.”

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