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Tag: Life Sciences

Tel Aviv University Researchers Present New Treatment for Ovarian Cancer

Using RNA-based nanodrugs the researchers achieve 80% survival rate in lab models.

Ovarian cancer ranks fifth in cancer deaths among women, accounting for more deaths than any other cancer of the female reproductive system. In a study conducted at Tel Aviv University researchers used protein CKAP5 (cytoskeleton-associated protein) for the first time as a therapeutic target for RNA-based nanodrugs. After identifying a genetically unstable mutation resistant to both chemotherapy and immunotherapy in the tissues of ovarian cancer, the researchers targeted these cells with lipid nanoparticles containing RNA for silencing CKAP5 – causing the cells to collapse and achieving an 80% survival rate in animal models.

 

“The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence [the CKAP5] protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell’s stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell.” – Dr. Sushmita Chatterjee

 

Targeted Delivery of RNA Drug

The breakthrough was achieved by a TAU research team led by Prof. Dan Peer of The Shmunis School of Biomedicine and Cancer Research, a global pioneer in the development of RNA-based drugs, Head of the Laboratory of Precision Nanomedicine, and TAU’s VP for R&D; and by Dr. Sushmita Chatterjee, post-doctoral student from India at Prof. Peer’s lab, in collaboration with Prof. David Sprinzak of The George S. Wise Faculty of Life Sciences and Prof. Ronen Zaidel-Bar of the Sackler Faculty of Medicine. The study was funded by the Rivkin Foundation for Ovarian Cancer Research and the Shmunis Family Foundation. The results were published in the leading scientific journal Science Advances.

“The protein CKAP5 has never been studied with relation to the fight against cancer, simply because there was no known way to silence it,” explains Dr. Chatterjee. “The lipid nanoparticles developed by Prof. Peer enabled us for the first time to silence this protein through targeted delivery of an RNA drug. We proved that CKAP5, a protein responsible for the cell’s stability, can be silenced, and that this procedure collapses and destroys the entire cancer cell.”

 

Prof. Dan Peer

“Something Like a Dominoes Game”

At the second stage of the study the researchers tested the new CKAP5-silencing RNA drug on 20 types of cancer. Some cancer cells proved more sensitive than others to this procedure. Cancers displaying high genetic instability, which are usually highly resistant to chemotherapy, were found to be especially sensitive to the silencing of CKAP5.

 

“As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer’s structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications (…)” – Prof. Dan Peer

 

“All cancer cells are genetically unstable,” says Dr. Chatterjee. “Otherwise, they would be healthy, not cancerous. However, there are different levels of genetic instability. We found that cancer cells that are more unstable, are also more affected by damage to CKAP5.  Our drug pushed them to their limit, and essentially destroyed their structure. Our idea was to turn the trait of genetic instability into a threat for these cells, by using RNA to silence the flawed protein. We demonstrated for the first time that CKAP5 can be used to kill cancer cells, and then observed the biological mechanism that causes the cancer cells to collapse in the protein’s absence.”

Equipped with these insights, the researchers tested the new drug in an animal model for ovarian cancer, achieving a survival rate of 80%.

“We chose ovarian cancer because it’s a good target,” explains Prof. Peer. “While highly resistant to both chemotherapy and immunotherapy, this type of cancer is very sensitive to the silencing of CKAP5. It should be emphasized that the CKAP5 protein is a new target in the fight against cancer. Targeting cell division is not new, but using RNA to target proteins that make up the cell’s skeleton (cytoskeleton) – this is a new approach and a new target that must be further investigated. As researchers, we are involved in something like a dominoes game: we always look for the one piece in the cancer’s structure that is so important, that if we pull it out the entire cell will collapse. CKAP5 is such a domino piece, and we are already working on more applications, this time in blood cancers.”

Bats Get “Pregnancy Brain” Too

New study finds that pregnancy affects bats’ sensing capabilities.

“Pregnancy brain” – sometimes called “brain fog” or “mommy brain” – refers to a pregnant woman’s forgetfulness during and shortly after pregnancy. And there have indeed been several studies pointing to an impairment of the cognitive abilities of pregnant women. Apparently, the condition does not just affect us humans: a new Tel Aviv University study reveals that bats, too, experience a decline in their ability to hunt and orient in space during pregnancy.

This impairment stems from the fact that they produce about 20 percent fewer calls, the sounds that allow them to orient themselves using echolocation, on top of flying at a slower pace and at a lower altitude. The researchers highlight the fact that, to the best of their knowledge, this is the first evidence of pregnancy affecting mammals’ sensory abilities.

 

“When a bat makes fewer calls, it gathers less information about the environment, its chance of colliding with objects increases, and its chance of finding food decreases — and this is at a time when the bat needs extra food to sustain the fetus in its womb.” Prof. Yossi Yovel

 

Affecting Bats’ Safety and Hunting

The study was led by Mor Taub, a research assistant in the laboratory of Prof. Yossi Yovel, head of Tel Aviv University’s Sagol School of Neuroscience and faculty member of the School of Zoology at The George S. Wise Faculty of Life Sciences. The study’s findings were published in the journal BMC Biology.

Mor Taub explains: “At the peak of pregnancy, bats carry about 20 percent more than their normal body weight, and it is clear that this excess weight impacts their flying capacity. In this study, we wanted to check whether and to what extent pregnancy affects bats’ echolocation ability, their sonar.”

“Bats’ sonar is based on the emitting and receiving of strong and frequent sounds in order to map their surroundings. To make these sounds, bats, like us humans, need to transfer high-pressure air from the lungs through the vocal cords, or vocal membranes, which involves many muscles, such as the chest and diaphragm. We wanted to see if the excess weight from pregnancy affects the production of sounds.”

 

Prof. Yossi Yovel

To this end, Prof. Yovel and his colleagues taught bats to search for and land on a small landing pad in a flight room in the bat laboratory at Tel Aviv University’s Garden for Zoological Research. They recorded the echolocation of two groups: pregnant bats and non-pregnant bats. The researchers found that the rate at which the pregnant bats emitted sounds was significantly lower than that of the control group, with 20% greater intervals between each sound.

Prof. Yovel explains that “bats change the rate of the sounds they make in accordance with the level of difficulty of the task. The average rate is about ten calls per second, but when the bat lands, this rate can increase to 100 calls per second. The pregnant bats produced sounds at a rate of only about seven per second and flew a little slower and lower.”

“Obviously, this slowing down is likely to affect their hunting. When a bat makes fewer calls, it gathers less information about the environment, its chance of colliding with objects increases, and its chance of finding food decreases — and this is at a time when the bat needs extra food to sustain the fetus in its womb. In the second phase of the study, we used a computer simulation to simulate the effect of the decreased rate of calls on the bats’ performance, and indeed, we saw that the slowed rate makes it more difficult for the bats to locate prey.”

 

“This is the only evidence we found in the professional literature showing that pregnancy affects mammals’ sensory abilities.” – Mor Taub

 

Preserving the Vulnerable

The bats in the experiment were of the Kuhl’s pipistrelle species, tiny bats that weigh only about six grams (when they are not pregnant). These bats are very common in Israel, and feed mainly on mosquitoes. Despite their weight, bats can live for decades, and their pregnancies are therefore also relatively long, lasting about four months.

Previous studies conducted on other species of bats have shown that during pregnancy, bats tend to change their diets. To date, the assumption was that this change in diet was due to the bats’ difficulty in flying, but the current study raises the possibility that the change may also be due to their sensory difficulty in detecting certain types of prey.

“This is the only evidence we found in the professional literature showing that pregnancy affects mammals’ sensory abilities,” says Mor Taub. “We assume that there are similar cases in other species as well, but this is the first time that researchers have been able to measure and demonstrate the impairment empirically. Beyond the scientific interest, it is important to preserve mammal species in the wild, especially during pregnancy and newborn care, since animals are particularly vulnerable during this period.”

Plants Emit Sounds – Especially When Stressed

In a world first, Tel Aviv University researchers record and analyze sounds distinctly emitted by plants.

Do you talk to your plants? While you may not be able to hear them, yaour plants could very well be chatting away as well (perhaps they are not such great listeners after all), and that’s especially true if they are having a bad day (did you forget to water them again?). For the first time in the world, TAU researchers recorded and analyzed sounds distinctly emitted by plants. The click-like sounds, resembling the popping of popcorn, are emitted at a volume similar to human speech, but at high frequencies, beyond the hearing range of the human ear. The researchers: “We found that plants usually emit sounds when they are under stress, and that each plant and each type of stress is associated with a specific identifiable sound. While imperceptible to the human ear, the sounds emitted by plants can probably be heard by various animals, such as bats, mice, and insects.”

 

“From previous studies we know that vibrometers attached to plants record vibrations, but do these vibrations also become airborne soundwaves – sounds that can be recorded from a distance? Our study addressed this question, which researchers have been debating for many years.” Prof. Lilach Hadany

 

Resolving Old Scientific Controversy

The study was led by Prof. Lilach Hadany from the School of Plant Sciences and Food Security at The George S. Wise Faculty of Life Sciences, together with Prof. Yossi Yovel, Head of the Sagol School of Neuroscience and faculty member at the School of Zoology and the Steinhardt Museum of Natural History, and research students Itzhak Khait and Ohad Lewin-Epstein, in collaboration with researchers from the Raymond and Beverly Sackler School of Mathematical Sciences, the Institute for Cereal Crops Research, and the Sagol School of Neuroscience – all at Tel Aviv University. The paper was published in the prestigious scientific journal Cell.

“From previous studies we know that vibrometers attached to plants record vibrations,” says Prof. Hadany. “But do these vibrations also become airborne soundwaves – sounds that can be recorded from a distance? Our study addressed this question, which researchers have been debating for many years.”

WATCH: Prof. Yossi Yovel and Prof. Lilach Hadany on their findings

 

At the first stage of the study the researchers placed plants in an acoustic box in a quiet, isolated basement with no background noise. Ultrasonic microphones recording sounds at frequencies of 20-250 kilohertz (the maximum frequency detected by a human adult is about 16 kilohertz) were set up at a distance of about 10cm from each plant. The study focused mainly on tomato and tobacco plants, but wheat, corn, cactus and henbit were also recorded.

 

 

“Our findings suggest that the world around us is full of plant sounds, and that these sounds contain information – for example about water scarcity or injury (…) We believe that humans can also utilize this information, given the right tools – such as sensors that tell growers when plants need watering.” – Prof. Lilach Hadany

 

 

Mapping Plants’ Complaints with AI

Before placing the plants in the acoustic box, the researchers subjected them to various treatments: some plants had not been watered for five days, in some the stem had been cut, and some were untouched. Prof. Hadany explains that their intention was to test whether the plants emit sounds, and whether these sounds are affected in any way by the plant’s condition: “Our recordings indicated that the plants in our experiment emitted sounds at frequencies of 40-80 kilohertz. Unstressed plants emitted less than one sound per hour, on average, while the stressed plants – both dehydrated and injured – emitted dozens of sounds every hour.”

The recordings collected in this way were analyzed by specially developed machine learning (AI) algorithms. The algorithms learned how to distinguish between different plants and different types of sounds, and were ultimately able to identify the plant and determine the type and level of stress from the recordings. Moreover, the algorithms identified and classified plant sounds even when the plants were placed in a greenhouse with a great deal of background noise.

In the greenhouse, the researchers monitored plants subjected to a process of dehydration over time and found that the quantity of sounds they emitted increased up to a certain peak, and then diminished.

“In this study we resolved a very old scientific controversy: we proved that plants do emit sounds!” says Prof. Hadany. “Our findings suggest that the world around us is full of plant sounds, and that these sounds contain information – for example about water scarcity or injury. We assume that in nature the sounds emitted by plants are detected by creatures nearby, such as bats, rodents, various insects, and possibly also other plants – that can hear the high frequencies and derive relevant information. We believe that humans can also utilize this information, given the right tools – such as sensors that tell growers when plants need watering. Apparently, an idyllic field of flowers can be a rather noisy place. It’s just that we can’t hear the sounds.”

In future studies the researchers will continue to explore a range of intriguing questions, such as: What is the mechanism behind plant sounds? How do moths detect and react to sounds emitted by plants? Do other plants also hear these sounds? Stay tuned. 

 

The research team

“Super Seaweed” Produces Natural Health Compounds and Medicine from the Sea

New Israeli technology could lead to anti-cancer, anti-diabetic, anti-inflammatory, anti-viral and antibiotic treatments.

After developing an innovative technology that enables the growth of seaweed enriched with proteins and minerals such as zinc, iron, iodine, magnesium, and calcium for humans and animals, researchers from Tel Aviv University’s School of Zoology at The George S. Wise Faculty of Life Sciences and the Israel Oceanographic and Limnological Research Institute (IOLR) have made a new advancement: They succeeded in significantly increasing the ability of seaweed to produce healthy natural substances, focusing on enhancing the production of bio-active compounds that offer medical benefits to humans, such as antioxidants – the concentration of which was doubled in the seaweed; natural sunscreens – its concentration tripled; and unique protective pigments of great medical value, the concentration of which increased by ten-fold.

The study was carried out with the innovative and sustainable approach of integrated aquaculture, which combines seaweed with fish cultivation, upgrading the seaweed while at the same time helping to purify the seawater and minimizing negative environmental impacts. According to the researchers, these findings may serve the pharmaceutical, cosmetics, food, and nutritional supplement industries.  

Manufacturers of Valuable Compounds

The new development was led by Ph.D. student Doron Ashkenazi of Tel Aviv University and the Israel Oceanographic and Limnological Research Institute, under the guidance of Prof. Avigdor Abelson of Tel Aviv University’s School of Zoology and Prof. Alvaro Israel of the IOLR in Haifa, in collaboration with other leading researchers from Israel and around the world, including Guy Paz from IOLR; organic chemistry expert Dr. Shoshana Ben-Valid; Dr. Eitan Salomon from the National Center for Mariculture in Eilat; and Prof. Félix López Figueroa, Julia Vega, Nathalie Korbee, and Marta García-Sánchez from Malaga University in Spain. The article was published in the scientific journal Marine Drugs.

 

Ph.D. student Doron Ashkenazi (left) and Prof. Avigdor Abelson (right)

Doron Ashkenazi explains that “seaweed, also known as macroalgae, are marine plants that form the basis of the coastal marine ecosystem. The seaweed absorb carbon dioxide and release oxygen into the environment. They purify the water, provide food, habitat, and shelter for numerous species of fish and invertebrates. Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans. The seaweed living in the intertidal zone face extreme stress conditions, which include changes in salinity, temperature, desiccation [loss of moisture] conditions, changes in the availability of nutrients and high exposure to solar radiation, especially in the ultraviolet (UV) range.”

 

“Not many know that seaweed also produce a wide variety of distinct bio-active compounds that are beneficial to humans.” Doron Ashkenazi

 

To survive, the seaweed has developed a unique set of chemical defense mechanisms – natural chemicals that help them cope with these harsh environments. They are highly efficient natural factories that produce valuable substances that may offer significant benefits to humans.

In the current study, they sought to examine whether and how it is possible to increase and maximize the seaweed’ production of bio-active compounds, and secondary metabolites, that offer significant health benefits. These substances include antioxidants, protective pigments, and natural UV radiation filters.

 

A dedicated aquaculture system where the researchers grew three local species of algae

Future Looking Greener Than Ever?

To this end, the researchers developed an original and practical cultivation approach, whereby three local seaweed – Ulva, Gracilaria and Hypnea – were initially grown alongside fish effluents, and subsequently exposed to stressors including high irradiance, nutrient starvation, and high salt content.

They investigated how these changes affected the concentration of specific valuable biomaterials in the seaweed, to enhance their production. The results were impressive: antioxidant levels had doubled, seaweed natural sunscreen molecules tripled, and protective pigments were increased by ten-fold. “We developed optimal cultivation conditions and invented a new and clean way to increase the levels of healthy natural bio-active compounds in seaweed to an unprecedented level,” says Ashkenazi. “We in fact produced ‘super seaweed’ tailor designed to be utilized by the emerging health industries for food and health applications.”

 

“In the future, humanity will focus on creating science-based environmental solutions (…) technologies that promote recycling and the sound use of natural resources without overexploiting them.” Doron Ashkenazi  

 

The researchers believe that in the future it will be possible to use their cultivation approach to elevate in seaweed additional natural materials with important medical properties, such as anti-cancer, anti-diabetic, anti-inflammatory, anti-viral, and ant-biotic substances.

They also emphasize that seaweed aquaculture is environmentally friendly, preserving the ecological balance, and reducing environmental risks by minimizing excessive amounts of pollutants caused by humans, reducing the emission of greenhouse gases, and lowering the carbon footprint. In this way, seaweed aquaculture can help cope with global environmental challenges such as pollution, habitat loss, and the climate crisis.

“In the future, humanity will focus on creating science-based environmental solutions, like the one we offer in this study – technologies that promote recycling and the sound use of natural resources without overexploiting them. Our study demonstrates how we can enjoy nature without harming it,” concludes Ashkenazi.

World’s First mRNA Vaccine Against Deadly Bacteria

Israeli researchers develop vaccine that is 100% effective against bacteria lethal to humans.

For the first time worldwide, a team of researchers from Tel Aviv University and the Israel Institute for Biological Research have developed an mRNA-based vaccine that is 100% effective against a type of bacteria that is lethal to humans. The study, conducted in a lab model, demonstrated that all treated models were fully protected against the bacteria. The researchers believe their new technology can enable rapid development of effective vaccines for bacterial diseases, including diseases caused by antibiotic-resistant bacteria, for example in case of a new fast-spreading pandemic.

 

“In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria.” Dr. Edo Kon

 

Quickly Developed

The study was led by Tel Aviv University’s Dr. Edo Kon and Prof. Dan Peer, VP for R&D and Head of the Laboratory of Precision Nano-Medicine at The Shmunis School of Biomedicine and Cancer Research at The George S. Wise Faculty of Life Sciences, in collaboration with researchers from the Israel Institute for Biological Research: Dr. Yinon Levy, Uri Elia, Dr. Emanuelle Mamroud, and Dr. Ofer Cohen. The results of the study were published in the journal Science Advances.

“So far, mRNA vaccines, such as the COVID-19 vaccines which are familiar to all of us, were assumed to be effective against viruses but not against bacteria,” explains Dr. Edo Kon. “The great advantage of these vaccines, in addition to their effectiveness, is the ability to develop them very quickly: once the genetic sequence of the virus SARS-CoV2 (COVID-19) was published, it took only 63 days to begin the first clinical trial. However, until now scientists believed that mRNA vaccines against bacteria were biologically unattainable. In our study we proved that it is, in fact, possible to develop mRNA vaccines that are 100% effective against deadly bacteria.”

 

Running RNA gel

Combining Breakthrough Strategies

The researchers explain that viruses depend on external (host) cells for their reproduction. Inserting its own mRNA molecule into a human cell, a virus uses our cells as a factory for producing viral proteins based on its own genetic material, namely replicates of itself.

In mRNA vaccines this same molecule is synthesized in a lab, then wrapped in lipid nanoparticles resembling the membrane of human cells. When the vaccine is injected into our body, the lipids stick to our cells, and consequently the cells produce viral proteins. The immune system, becoming familiar with these proteins, learns how to protect our body in the event of exposure to the real virus.

Since viruses produce their proteins inside our cells, the proteins translated from the viral genetic sequence resemble those translated from the lab-synthesized mRNA.

 

“If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines.” Prof. Dan Peer

 

Bacteria, however, are a whole different story: They don’t need our cells to produce their own proteins. And since the evolutions of humans and bacteria are quite different from one another, proteins produced in bacteria can be different from those produced in human cells, even when based on the same genetic sequence.

“Researchers have tried to synthesize bacterial proteins in human cells, but exposure to these proteins resulted in low antibodies and a general lack of protective immune effect, in our bodies,” explains Dr. Kon. “This is because, even though the proteins produced in the bacteria are essentially identical to those synthesized in the lab, being based on the same ‘manufacturing instructions’, those produced in human cells undergo significant changes, like the addition of sugars, when secreted from the human cell.”

“To address this problem, we developed methods to secrete the bacterial proteins while bypassing the classical secretion pathways, which are problematic for this application. The result was a significant immune response, with the immune system identifying the proteins in the vaccine as immunogenic bacterial proteins. To enhance the bacterial protein’s stability and make sure that it does not disintegrate too quickly inside the body, we buttressed it with a section of human protein. By combining the two breakthrough strategies we obtained a full immune response.”

WATCH: Prof. Dan Peer and Dr. Edo Kon on the world’s first mRNA vaccine for deadly bacteria

 

Solution to Antibiotic-resistant Bacteria?

“There are many pathogenic bacteria for which we have no vaccines,” adds Prof. Peer. “Moreover, due to excessive use of antibiotics over the last few decades, many bacteria have developed resistance to antibiotics, reducing the effectiveness of these important drugs. Consequently, antibiotic-resistant bacteria already pose a real threat to human health worldwide. Developing a new type of vaccine may provide an answer to this global problem.”

“In our study, we tested our novel mRNA vaccine in animals infected with a deadly bacterium. Within a week, all unvaccinated animals died, while those vaccinated with our vaccine remained alive and well. Moreover, in one of our vaccination methods, one dose provided full protection just two weeks after it was administered. The ability to provide full protection with just one dose is crucial for protection against future outbreaks of fast-spreading bacterial pandemics. It is important to note that the COVID-19 vaccine was developed so quickly because it relied on years of research on mRNA vaccines for similar viruses. If tomorrow we face some kind of bacterial pandemic, our study will provide a pathway for quickly developing safe and effective mRNA vaccines.”

The study was funded by research grants from the European Union (ERC; EXPERT) and the Shmunis Family (for Prof. Peer).

Do We Need ‘Junk DNA’?

Researchers offer possible reason why neutral sequences in the genome of living creatures continue to exist millions of years later.

A new model developed at Tel Aviv University offers a possible solution to the scientific question of why neutral sequences, sometimes referred to as “junk DNA”, are not eliminated from the genome of living creatures in nature and continue to exist within it even millions of years later.

According to the researchers, the explanation is that junk DNA is often located in the vicinity of functional DNA. Deletion events around the borders between junk and functional DNA are likely to damage the functional regions and so evolution rejects them. The model contributes to the understanding of the huge variety of genome sizes observed in nature.

Border Induced Selection

The model describes a phenomenon which the team of researchers refer to as “border induced selection,” and was developed under the leadership of PhD student Gil Loewenthal in the laboratory of Prof. Tal Pupko from the Shmunis School of Biomedicine and Cancer Research at the The George S. Wise Faculty of Life Sciences and in collaboration with Prof. Itay Mayrose, also from TAU’s Faculty of Life Sciences. The study was published in the journal Open Biology.

Throughout evolution, the size of the genome in living creatures in nature changes. For example, some salamander species have a genome ten times larger than the human genome. “The rate of deletions and short insertions, dubbed ‘indels’, is usually measured by examining pseudogenes,” explains Prof. Pupko. “Pseudogenes are genes that have lost their function, and in which there are frequent mutations, including deletions and insertions of DNA segments.”

In previous studies that characterized the indels, it was found that the rate of deletions is greater than the rate of additions in a variety of creatures including bacteria, insects, and even mammals such as humans.

 

Prof. Tal Pupko

 

Reverse Bias for Short Segments

The question the researchers sought to answer is how the genomes are not deleted when the probability of DNA deletion events is significantly greater than DNA addition events: “We have provided a different view to the dynamics of evolution at the DNA level,” says Loewenthal. “When measuring the rate of indels there will be more deletions, but the measurements are carried out in pseudogenes which are quite long sequences. We assert that in shorter neutral segments, deletions would likely remove adjacent functional segments which are essential for the functioning of the organism, and they will therefore be rejected [through ‘border-induced selection’]. Accordingly, we assert that when the segment is short, there will be a reverse bias – there will be more insertions than deletions – and therefore short neutral segments are usually retained.”

“In our study, we simulated the dynamics of indels, while taking into account the effect of ‘border-induced selection,’ and compared the simulation results to the distribution of human intron lengths (introns are DNA segments in the middle of a protein-coding gene, which themselves do not code for a protein). A good match was obtained between the results of the simulations and the distribution of lengths observed in nature, and we were able to explain peculiar phenomena in the length distribution of introns, such as the large variation in intron lengths, as well as the complex shape of the distribution which does not look like a standard bell curve.”

New Snake Family Identified

As far as researchers are aware the Micrelapidae family includes only three species, one in Israel and neighboring countries, and two in East Africa.

An extensive international study identified a new family of snakes: Micrelapidae. According to the researchers, Micrelaps, small snakes usually with black and yellow rings, diverged from the rest of the evolutionary tree of snakes about 50 million years ago. As far as they know, the new family includes only three species, one in Israel and neighboring countries, and two in East Africa.

 

“Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes.” Prof. Shai Meiri

 

Exploring the Micrelaps’ Family Tree

The study was conducted by Prof. Shai Meiri of TAU’s School of Zoology, The George S. Wise Faculty of Life Sciences, and of The Steinhardt Museum of Natural History Museum, as well as researchers from Finland, the USA, Belgium, Madagascar, Hong Kong, and Israel. The paper was published in Molecular Phylogenetics and Evolution.

“Today we tend to assume that most large groups of animals, such as families, are already known to science, but sometimes we still encounter surprises, and this is what happened with Micrelapid snakes,” explains Prof Meiri.

“For years, they were considered members of the largest snake family, the Colubridae, but multiple DNA tests conducted over the last decade contradicted this classification. Since then, snake researchers around the world have tried to discover which family these snakes belong to – to no avail. In this study we joined the scientific effort.”

The researchers used micro-CT technology – high-resolution magnetic imaging, to examine the snake’s morphology, focusing specifically on the skull. In addition, they applied methods of deep genomic sequencing – examining about 4,500 ultra-conserved elements, namely regions in the genome that take millions of years to exhibit any change.

Prof. Meiri explains that “in addition to the DNA of Micrelaps, we sampled DNA from various snake groups to which they might have belonged. This way, we discovered some unique genomic elements in Micrelaps, which were not found in any of the other groups.”

 

Prof. Shai Meiri

 

“Even through these snakes have been known for decades, they were mistakenly included in other families for many years.” Prof. Shai Meiri

 

Family Relocation

According to the researchers their findings indicate that Micrelaps diverged from the rest of the evolutionary tree of snakes about 50 million years ago. Since then, these snakes have evolved independently, as a distinct and separate family.

Apparently, this is a very small family, including only three species: two in Kenya and Tanzania in East Africa, and one in Israel and nearby regions (northern Jordan and the Palestinian Authority, southern Syria, and southern Lebanon). The geographic dispersion suggests that these snakes probably originated in Africa, and then, at some point in their history, some of them made their way north through the Great Rift Valley.

“In this study we were able to associate a new snake family – the Micrelapidae. Even through these snakes have been known for decades, they were mistakenly included in other families for many years. Since most animals have already been classified into well-defined families, such a discovery of a new family is quite a rare occurrence in modern science,” concludes Prof. Meiri.   

Featured image: Small with black and yellow rings, some 50 million years old. Meet the Micrelaps snake (photo: Alex Sablenco )

Prestigious Grant from the European Innovation Council Awarded to Tel Aviv University’s Research Team

Dr. Iftach Nachman from the Faculty of Life Sciences leads the Israeli research team, as part of an international consortium.

The European Innovation Council Pathfinder Challenges program announced a 4.95M Euro funding to an international consortium from six countries. Dr. Iftach Nachman from the School of Neurobiology, Biochemistry & Biophysics at The George S. Wise Faculty of Life Sciences at Tel Aviv University leads the Israeli research team. The funding is given to an international consortium for the development of the Supervised Morphogenesis in Gastruloids (SUMO) project.

As part of the SUMO project, the researchers develop embryo like models (called ‘gastruloids’) based on pluripotent stem cells, to mimic cardiac and gastric tissues. With the help of advanced microscopy and machine learning, the consortium aims to make the gastruloids more robust and reproducible. The researchers hope that those models could be implemented in drug scanning and study of mutations in the future, and thus be a viable substitute to the use of lab animals.

Dr. Iftach Nachman: “In recent years the research field of embryonic models is seeing a huge boost. One of the main problems with growing such in-vitro stem-cell based models (and organoids in general) is the great variability between the different samples. We need to learn how to tame and control this variability to realize the promise of those models to the fields of medicine and basic science. This grant will enable us to deepen the scope of the research in this field.”

The SUMO consortium unites researchers from the University Hospital Oslo, Norway (HTH director: Stefan Krauss, coordinator), Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG) (Jesse Veenvliet), Imperial College London, UK (HTH PI: Molly Stevens), University of Glasgow, UK (HTH PI: Nikolaj Gadegaard), Tel Aviv University, Israel (Iftach Nachman), Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Germany (Jens von Kries) and University of Oslo (HTH PI: Jan Helge Solbakk). 

 

European Innovation Council - Funded by the European Union

Prof. Dan Peer Appointed as Member of the Prestigious American National Academy of Engineering

In recognition of his groundbreaking research developing unique strategies for delivering RNA molecules.

The National Academy of Engineering (NAE), one of the three National Academies in the USA (Sciences, Medicine, and Engineering), has announced the appointment of Prof. Dan Peer from Tel Aviv University, currently TAU’s VP R&D and Head of the Nanomedicine Lab at The Shmunis School of Biomedicine and Cancer Research, The George S. Wise Faculty of Life Sciences and from The Department of Materials Science and Engineering at The Iby and Aladar Fleischman Faculty of Engineering, as Member of the Academy, in recognition of his groundbreaking research developing unique strategies for delivering RNA molecules.

Prof. Peer is a trailblazing scientist and pioneer in developing RNA-based molecular drugs for a wide range of diseases, including inflammatory bowel diseases; blood, brain, and ovarian cancers; and rare genetic diseases.

He also investigates the use of RNA molecules as vaccines for viral diseases and develops nano-scale drug carriers that can target specific cells selectively. Among his landmark achievements: Prof. Peer and his lab were first in the world to demonstrate a process for production of medicinal proteins by RNA molecules in animals, as well as use of short RNA to silence genes in immune cells, and gene editing by means of nanoparticles that target specific cells when injected into the bloodstream.

In addition to his innovative research, Prof. Peer serves in several leading positions: TAU’s VP R&D, Chair of Ramot – the technology transfer company of Tel Aviv University, and Chair of TAU Ventures. Prof. Peer is also a member of the American Society for Cell Biology and the American Association for the Advancement of Science. Over the years he has contributed to many inventions (over 130 patents filed), commercialized through several companies, and established startups in Israel, the UK, and the USA.

Featured image: Prof. Dan Peer (Photo Credit: TAU)

Light Pollution is Killing Desert Rodents

New study shows that artificial light at night can be harmful to ecosystems, biodiversity, and human health.

A new study from Tel Aviv University’s School of Zoology tested the impact of prolonged low-intensity light pollution on two species of desert rodents: the diurnal golden spiny mouse, and the nocturnal common spiny mouse. The findings were highly disturbing: on two different occasions, entire colonies exposed to ALAN (Artificial Light At Night) died within days, and reproduction also decreased significantly compared to control groups. According to the researchers, the results show clearly for the first time that light pollution can be extremely harmful to these species, and suggest they may be harmful to ecosystems, biodiversity, and even human health.

 

“According to latest studies, about 80% of the world’s human population is exposed to ALAN, and the area affected by light pollution grows annually by 2-6%. In a small and overcrowded state like Israel, very few places remain free of light pollution.” Hagar Vardi-Naim

 

Humans Changed the Rules

The study was led by Prof. Noga Kronfeld-Schor, Chief Scientist of Israel’s Ministry of Environmental Protection, and PhD student Hagar Vardi-Naim, both from TAU’s School of Zoology and the Steinhardt Museum of Natural History.  The paper was published in Scientific Reports.

“We have been studying these closely related rodent species for years.  They both live in Israel’s rocky deserts: the golden spiny mouse (Acomys russatus) is diurnal [active during the day], and the common spiny mouse (A. cahirinus) in nocturnal [active during the night],” explains Prof. Kronfeld-Schor. “The two species share the same natural habitat but use it at different times to avoid competition. By comparing closely related species that differ in activity times, we gain new insights into the biological clock and its importance to the health of both animals and humans.”

Hagar Vardi-Naim notes that, “in most species studied to date, including humans, the biological clock is synchronized by light. This mechanism evolved over millions of years in response to the daily and annual cycles of sunlight – day and night and their varying lengths that correspond to the change of seasons. Different species developed activity patterns that correspond to these changes in light intensity and daylength and developed anatomical, physiological and behavioral adaptations suitable for day or night activity and seasonality.”

“However, over the last decades, humans have changed the rules by inventing and extensively using artificial light, which generates light pollution. According to latest studies, about 80% of the world’s human population is exposed to ALAN, and the area affected by light pollution grows annually by 2-6%. In a small and overcrowded state like Israel, very few places remain free of light pollution. In our study, we closely monitored the long-term effects of ALAN on individuals and populations under semi-natural conditions.”

 

“We had seen no preliminary signs (…) We assume that exposure to ALAN had impaired the animals’ immune response, leaving them with no protection against some unidentified pathogen [organism causing disease to its host].” Prof. Noga Kronfeld-Schor

 

 

Prof. Noga Kronfeld-Schor

Dramatic Turn of Events

In the study, the researchers placed 96 spiny mice, males and females in equal numbers, in eight spacious outdoor enclosures at TAU’s Zoological Research Garden. The enclosures simulated living conditions in the wild: all animals were exposed to natural environmental conditions, including the natural light/dark cycle, ambient temperatures, humidity, and precipitation. Each enclosure contained shelters, nesting materials and access to sufficient amounts of food. The experimental enclosures were exposed to low-intensity ALAN (like a streetlamp in urban areas) of different wavelengths (colors) for 10 months: two enclosures were exposed to cold white light, two to warm white (yellowish) light, and two to blue light, while two of the enclosures remained dark at night and served as controls. All animals were marked to enable accurate monitoring of changes in behavior and physical condition. The experiment was conducted twice in two successive years.

“The average life expectancy of spiny mice is 4-5 years, and our original plan was to monitor the effects of ALAN on the same colonies, measuring the effects on reproductive output, wellbeing and longevity,” says Prof. Kronfeld-Schor. “But the dramatic results thwarted our plans: on two unrelated occasions, in two different enclosures exposed to white light, all animals died within several days. We had seen no preliminary signs, and autopsies at TAU’s Faculty of Medicine and the Kimron Veterinary Institute in Beit Dagan revealed no abnormal findings in the dead spiny mice. We assume that exposure to ALAN had impaired the animals’ immune response, leaving them with no protection against some unidentified pathogen. No abnormal mortality was recorded in any of the other enclosures, and as far as we are aware, no similar event has ever been documented by researchers before.”

 

“Our findings show that light pollution, especially cold white and blue light, increases mortality and disrupts reproduction, and thus may be detrimental to the fitness and survival of species in the wild. This adverse effect can have far-reaching consequences at the current wide distribution of light pollution.” Prof. Noga Kronfeld-Schor

 

Disrupted Reproduction

Other findings also indicated that exposure to ALAN disrupts the reproductive success of spiny mice: “In the wild both species of spiny mice breed mainly during summer, when temperatures are high, and the newborn pups are most likely to survive,” shares Hagar Vardi-Naim. “Artificial light, however, seemed to confuse the animals. The common spiny mice began to breed year-round but produced a lower number of pups per year. Pups born during winter are not expected to survive in nature, which would further reduce the species’ reproductive success in the wild.”

“The reproduction of golden spiny mice was affected in a different way: colonies exposed to ALAN continued to breed in the summer, but the number of young was reduced by half compared to the control group, which continued to thrive and breed normally. These findings are in accordance with the fact that in seasonal long day breeders the cue for reproduction is day length.”

Additional tests revealed that exposure to ALAN caused physiological and hormonal changes – most significantly in the level of cortisol, an important stress hormone involved in the regulation and operation of many physiological pathways, including the regulation of the immune system. Lab tests indicated that exposure to blue light increased cortisol levels of golden spiny mice, while white light reduced cortisol levels of golden spiny mice males in winter.

“Our findings show that light pollution, especially cold white and blue light, increases mortality and disrupts reproduction, and thus may be detrimental to the fitness and survival of species in the wild. This adverse effect can have far-reaching consequences at the current wide distribution of light pollution. Our clear results are an important step toward understanding the impact of light pollution on biodiversity and will help us promote science-based policies, specifically with regard to the use of artificial light in both built and open areas. In future studies we plan to investigate what caused the extensive deaths in the enclosures exposed to ALAN, focusing on the effect of light pollution exposure on the immune system,” concludes Prof. Kronfeld Schor.

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