A  team of Tel Aviv University researchers led by Dr. Adi Stern of the School of Molecular Cell Biology and Biotechnology at TAU’s George S. Wise Faculty of Life Sciences have conducted the first large-scale genomic sequencing of the novel coronavirus strain that has infected to date over 16,500 people in Israel. The scientists harnessed their genomic map to pinpoint mutations indicating where the virus originated from and later spread to within Israel. The study is based on an analysis of the genomic sequences of over 200 patients at hospitals across Israel, who together constitute a representative sample of the general population. TAU doctoral students Daniel Miller, Noam Harel, Talia Kostin, Omer Tirosh and Moran Meir conducted the research for the study in collaboration with scientists at Emory University, Gertner Institute, Chaim Sheba Medical Center, the Holon Institute of Technology, Assuta Hospital Ashdod, Hadassah Ein Karem Medical Center, Soroka Medical Center, Barzilai Medical Center, Poriya Medical Center, and the Genome Center at the Technion Institute of Technology.

The origins of coronavirus

“The novel coronavirus is characterized by mutations that occur at a set pace,” explains Dr. Stern. “These mutations do not affect the virus, i.e. it remains stable, but these mutations can help us trace the chain of infection from country to country. After the pandemic broke out in Wuhan, for example, one or two mutations occurred, and one virus with a mutation may have migrated to Europe where it experienced additional mutations, and from there it traveled to the United States, and so on. “We can look at these mutations as a kind of barcode that helps us keep track of the progression and transformation of the coronavirus as it moves from country to country.” To obtain a clear picture of the origin of infection in Israel, the researchers compared the genomic sequences of local patients to some 4,700 genomic sequences taken from patients around the world. They found that more than 70% of the patients had been infected by a coronavirus strain that originated in the U.S. The remaining nearly 30% of infections were imported from Europe and elsewhere: Belgium (8%), France (6%), England (5%), Spain (3%), Italy (2%), the Philippines (2%), Australia (2%) and Russia (2%). According to Dr. Stern, the new genomic map provides insight into the precise spread of the novel coronavirus within Israel. Until now, any assessment of the spread of infection relied on such subjective parameters as patient feedback. The new research will be able to expose the rate of infection in a household, in an apartment building, in a school, in a neighborhood, and more. It will also provide early detection of super spreaders – people who travel far and wide and infect a large number of people – and could even identify major events with the potential to trigger widespread infection.

The importance of 10%

“Going forward, the data obtained from genomic sequencing will serve as an important basis for informed decisions about which institutions to close, for what amount of time, and in which format,” says Dr. Stern. With policymakers in mind, the researchers developed a complex statistical model based on genomic sequencing that estimates the epidemiological parameters of viral spread. The model shows that the rate of infection decreased significantly following strict quarantine measures taken in Israel and highlights a major discrepancy between the number of people each coronavirus patient infected. The model also estimates that over 80% of coronavirus cases in Israel were the direct result of only 10% of the coronavirus patients in Israel, meaning that these 10% were, in fact, super-spreaders. According to the model and to the genomic sequencing, Dr. Stern says that no more than 1% of the population in Israel contracted the virus – a far cry from herd immunity. “In our study, we performed the first massive genomic sequencing of the coronavirus in Israel,” she concludes. “This technology and the information it provides is of great importance for understanding the virus and its spread in the population, as a scientific and objective basis for local and national decision-making. The data obtained from the research can greatly help policymakers on issues such as closures and quarantines. In doing so, the study makes a significant contribution to dealing with the epidemic in Israel, and, more importantly: We have developed tools that will allow us to cope, in real time, with the next outbreak that may occur.”

Tel Aviv University researchers have developed a safe and accurate 3D imaging method to identify sperm cells moving at a high speed. The research was led by Prof. Natan Shaked of the Department of Biomedical Engineering at TAU’s Faculty of Engineering together with TAU doctoral student Gili Dardikman-Yoffe. The new technology could provide doctors with the ability to select the highest-quality sperm for injection into an egg during IVF treatment, potentially increasing a woman’s chance of becoming pregnant and giving birth to a healthy baby. “The IVF procedure was invented to help fertility problems,” explains Prof. Shaked. “The most common type of IVF today is intra-cytoplasmic sperm injection (ICSI), which involves sperm selection by a clinical embryologist and injection into the woman’s egg. To that end, an effort is made to select the sperm cell that is most likely to create a healthy embryo.”

Choosing the right cells to make a baby

Under natural fertilization in the woman’s body, the fastest sperm to reach an egg is supposed to bear high-quality genetic material. Progressive movement allows this “best” sperm to overcome the veritable obstacle course of a woman’s reproductive system. “But this ‘natural selection’ is not available to the embryologist, who selects a sperm and injects it into the egg,” Prof. Shaked says. “Sperm cells not only move fast, they are also mostly transparent under regular light microscopy, and cell staining is not allowed in human IVF. Existing imaging technology that can examine the quality of the sperm’s genetic material may cause embryonic damage, so that too is prohibited. In the absence of more precise criteria, sperm cells are selected primarily according to external characteristics and their motility while swimming in water in a dish, which is very different from the natural environment of a woman’s body. “In our study, we sought to develop an entirely new type of imaging technology that would provide as much information as possible about individual sperm cells, does not require cell staining to enhance contrast, and has the potential for enabling the selection of optimal sperm in fertilization treatments.”

A hologram of sperm cells

The researchers chose light computed tomography (CT) technology for the unique task of sperm cell imaging. “In a standard medical CT scan, the device rotates around the subject and sends out X-rays that produce multiple projections, ultimately creating a 3D image of the body,” says Prof. Shaked. “In the case of the sperm, instead of rotating the device around this tiny subject, we relied on a natural feature of the sperm itself: Its head is constantly rotating during the forward movement. We used weak light (and not X-rays), which does not damage the cell. We recorded a hologram of the sperm cell during ultrafast movement and identified various internal components according to their refractive index. This creates an accurate, highly dynamic 3D map of its contents without using cell staining.” Using this technique, the researchers obtained a clear and accurate CT image of the sperm at very high resolution in four dimensions: three dimensions in the space at resolution of less than half a micron (one micron equals one millionth of a meter) and the exact time (motion) dimension of the second sub-millisecond. “Our new development provides a comprehensive solution to many known problems of sperm imaging,” Prof. Shaked says. “We were able to create high-resolution imaging of the sperm head while it was moving fast, without the need for stains that could harm the embryo. The new technology can greatly improve the selection of sperm cells in vitro, potentially increasing the chance of pregnancy and the birth of a healthy baby. “To help diagnose male fertility problems, we intend to use our new technique to shed light on the relationship between the 3D movement, structure and contents of sperm and its ability to fertilize an egg and produce a viable pregnancy,” Prof. Shaked concludes. “We believe that such imaging capabilities will contribute to other medical applications, such as developing efficient biomimetic micro-robots to carry drugs within the body.”

Ramot, Tel Aviv University’s technology transfer company, and Neovii, a Swiss-based biopharmaceutical company and a member of Israel-based Neopharm Group, announced today that they have signed a research and license agreement to develop a novel and potentially life-saving COVID-19 vaccine. Neovii will work in close collaboration with a team of scientists led by Prof. Jonathan Gershoni of TAU’s School of Molecular Cell Biology and Biotechnology. The agreement grants Neovii the exclusive right to develop and commercialize a novel and recently patented platform technology conceived by Prof. Gershoni for the rapid discovery of epitope-based vaccines. The collaboration is focused on the development of a first-in-class COVID-19 vaccine that reconstructs the coronavirus’s Receptor Binding Motif (RBM), a critical structure of its “spike” protein. The “spike” protein itself is the major surface protein that the virus uses to bind to the cellular receptor that acts as the doorway into the human cell. After the spike protein binds to the human cell receptor, the viral membrane fuses with the cell membrane, allowing the genome of the virus  to enter the cell and begin infection. “We have been working on coronaviruses for the last 15 years developing a method of reconstructing and reconstituting the RBM structure of the spike protein in SARS-CoV and subsequently in MERS-CoV,” explains Prof. Gershoni. “The moment the genome of the new virus was published in early January 2020, we began the process of reconstituting the RBM of SARS-CoV-2, the virus that causes COVID-19, and expect to have a reconstituted RBM of the new virus soon. This is the basis for the new vaccine, which could be ready for use within a year to a year and a half.”

Targeting the Achilles’ heel of coronavirus

“The smaller the target and the focus of the attack, the safer and greater the effectiveness of the vaccine,” he adds. “The virus takes far-reaching measures to hide its RBM from the human immune system, but the best way to ‘win the war’ is to develop a vaccine that specifically targets the virus’s RBM.” Keren Primor Cohen, Ramot CEO says: “We hope that through this collaboration with Neovii, it will be possible to produce an effective vaccine that targets the coronavirus’s Achilles’ heel and will accelerate the development of a protective vaccine against this global threat.” Jürgen Pohle, Neovii CEO, adds: “The outbreak of the COVID-19 pandemic has demonstrated how fragile and vulnerable our societies are in the face of a pandemic.  We are extremely excited about our collaboration with Professor Gershoni and TAU which provides Neovii with a first-in-class platform for the rapid development of promising vaccine candidates towards any future emerging pandemics including COVID-19. Furthermore, the COVID-19 vaccine is highly synergistic to Neovii’s core expertise in the development and manufacturing of passive polyclonal antibodies and provides an opportunity to bring a COVID-19 immunotherapy in a rapid manner.” Neovii’s long-standing and well-established experience and capabilities in developing, manufacturing and commercializing biopharmaceuticals will support the objective to have a vaccine ready for use in the general population on an accelerated timeline.

The coronavirus pandemic caught us off guard. Without any warning, it transformed our daily routines overnight and caused a global shock, which will take a long time to recover from. The climate crisis, on the other hand, has been a subject of discussion for scientists for many years. Are there any points at which these two threats connect? And will dealing with the immediate threat, the coronavirus, also lead to more ecological and considerate behavior towards the environment? Prof. Colin Price, head of the Porter School of Environmental Studies and Earth Sciences, created an online seminar on the topic and called on heads of state to take advantage of the opportunity we’ve been given to save the world from an irreversible crisis which is about to reach the point of no return.

Immediate sacrifice for a long-term solution

Since the beginning of the coronavirus crisis, we’ve realized in a few weeks how much power nature has, and how it can neutralize human systems. Entire populations and sectors have been shut down and defined as high risk, economies and medical systems have been paralyzed, prosperous industries are suddenly at the brink of collapse, disrupted supply chains and more.

“Everyone understands that we have to act swiftly around the coronavirus, in order to achieve a fair, long-term solution,” says Prof. Price, and immediately points out the similarity to an issue we’ve been dealing with for a long time – the climate crisis. “While the Corona crisis is mostly threatening to humans, the effects of the climate crisis, evident in deadly heat waves, huge fires, floods, storms and sea level rise, are hitting a much wider ‘target audience’. Animals, infrastructure, natural resources – everything is under threat. The main problem is that because the climate crisis is not immediate, like coronavirus, and because it’s not personal – it’s not taken seriously enough, and long-term solutions aren’t being considered.”

Professor Price referred to similar points in both crises, including the weight that must be given to the exponential curve of both, the speed with which we have to react in order to stop the destructive effects in time, and the immediate sacrifice that must be made to gain a better long-term outcome for future generations.

Change will be good for us and the environment

“There is no doubt that when we go back to normal after the coronavirus crisis, everything will be different,” says Prof. Price. “I estimate that thanks to online communication, we will see a decrease in the volume of business trips abroad and, as a result, the demand for oil will decrease. People will work more from home and there will no doubt be companies that adopt this format, and will completely give up paying office fees. There will be greater investment in new infrastructure in health systems, distance learning, local manufacturing and more changes that, if examined in the environmental aspect – are undoubtedly friendly to the natural resources we breathe and consume, which we want to protect.”

“If you ask me what we should learn from the current crisis, it’s first and foremost that we should listen to scientists. From the first day the virus broke out in China, they warned that it was an epidemic that would affect the whole world. So should we listen to the scientists who have been studying the climate crisis. I’ve been working in the field for 30 years and I can say for sure – people don’t listen. World leaders don’t listen.”

“We all need to understand the severity of the exponential curve, and understand the cost of our actions for the global village we live in, both on the coronavirus and climate issues. We have to remember that our actions on one side of the world affect people and the environment on the other.”

Lower the level of vulnerability and increase our resilience

According to Prof. Price, the role of governments is critical in managing the world response to both crises. “To reinvigorate the economy at the end of the Corona crisis, we have the opportunity to encourage funding, job allocation and investment in green technologies, for example in the public transport sector, to make it more efficient, cost-effective and green, to provide a more promising future and prevent the arrival of the next crisis.”

“The risk of a crisis, no matter if it’s an earthquake, fire or deadly virus, depends on three main variables: the threat itself, who is exposed to it and what level of vulnerability there is,” Prof. Price explains. “Once we manage to neutralize one of these variables, our chances of getting hurt are smaller.”

Watch the online seminar >

_{Prof. Colin Price}

Tel Aviv University has announced the establishment of the Center for Combating Pandemics, a first of its kind multidisciplinary epidemic research center, at an investment of tens of millions of shekels. Mr. Frank Lowy, an Australian businessman and philanthropist made a significant initial gift to the center. Meanwhile, many other philanthropic foundations have expressed interest in joining the initiative. The Center will bring together top experts from TAU’s diverse fields of knowledge: medicine, biology, mathematics, physics, economics, engineering, education, psychology and more. These researchers will work with counterparts at leading hospitals and academic institutions in Israel and around the world to advance research in the field with the ultimate aim of assisting the State of Israel in coping with future epidemics. Alongside its research activity, the Center will submit policy recommendations and papers to international policy makers, take part in international conferences, help draft informative material for public consumption and will provide scholarship and research grants to outstanding students and scholars. TAU President Prof. Ariel Porat: “For the first time, the innovative research center will allow researchers to join forces, pool their resources and examine the implications of the pandemic from different perspectives. The collaborative efforts will enable researchers to produce a bird’s eye view that will offer insight into the best ways to deal with future crises of this kind.”

Israel’s Health Ministry has approved opening a Tel Aviv University COVID-19 testing lab, which will allow Israel to perform 1,600 coronavirus tests a day. The TAU lab, headed Prof. Ariel Munitz of TAU’s Sackler Faculty of Medicine, was born virtually overnight of the interdisciplinary efforts of some 30 TAU researchers, graduate students and management staff of the Sackler School of Medicine and the George S. Wise Faculty of Life Sciences. “Immediately upon the outbreak of the Corona crisis, TAU focused all its resources on the national task of eradicating the epidemic,” says Tel Aviv University President Prof. Ariel Porat. “But now we have decided to go beyond what is customary in the academic world and open a fully operational laboratory for coronavirus testing. We are supplying top experts with the most innovative equipment and technology for the benefit of the Health Ministry and the public, all of whom have one clear goal – to defeat this virus.”

A medical marvel in 80 hours

The decision to establish a lab was made shortly after the coronavirus crisis broke out in Israel. From start to finish, the lab was built in a record 80 hours, with construction kicking off on Tuesday, March 24th, at 7 AM, and finishing Friday, March 27th. A Health Ministry official yesterday reviewed the lab to ensure that it meets health and safety protocols, and the lab is now fully operational. “We realized immediately how critical testing was and how we at the University could contribute to Israel’s diagnostic landscape,” explains Prof. Munitz. “We contacted University management, who got involved immediately and quickly approved a budget for the project. It was not an easy decision. It was unclear whether the Health Ministry would approve, and we did not know exactly what the protocol was or what was required — but we knew we needed to act. The safety of the team operating the lab is and remains our highest priority, and we are taking every necessary precaution in strict alignment with Health Ministry regulations. I have no doubt that our collaboration with the Health Ministry will greatly assist in advancing the national testing system.”

The race to develop effective antibody-based treatments for COVID-19 is advancing at a rapid pace. Now, a Tel Aviv University laboratory reports it has successfully isolated two antibodies that would neutralize the virus’s ability to infect human cells. The two suitable antibodies were identified in patients recovering from COVID-19, according to Dr. Natalia Freund who heads the Laboratory for Human Antibody Responses at TAU’s Sackler Faculty of Medicine. “The use of antibodies bears significant potential as a treatment for high-risk coronavirus patients and as a preventative measure for at-risk groups, like medical workers and essential employees, exposed to the virus,” she explains.

The weak link in the virus chain

In the long run, identifying effective antibodies against virus neutralization could also accelerate the development of vaccines for the disease. Dr. Freund, who together with her team pinpointed the antibodies in blood samples of recovering patients, say that antibodies would be key to identifying the elusive vulnerable Achilles’ heel of the virus, which scientists have identified as somewhere along its spike protein, the structure that allows it to break into a cell. Dr. Freund is collaborating with researchers in San Diego to test the efficacy of antibody treatments in animal models against a live active virus. The trials are scheduled to take place this month. Only if and when the trials are successful in animal models will the option of clinical trials be considered. “If we complete the trials successfully and are able to eventually develop this treatment, it could be used to help treat at-risk patients such as the elderly or immunocompromised patients. Antibodies can also remain active in the blood for many weeks – up to two months – so injecting antibodies can afford medical teams and other at-risk groups temporary protection against the virus.”