Non-invasive, immediate, and automaticIn 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.”
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.
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
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.
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).
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 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.
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.”