Tel Aviv University researchers open new doors for applying personalized medicine to infectious diseases, moving beyond cancer and Alzheimer's
- Life Sciences
In the world of healthcare, personalized medicine has made significant strides in certain disease areas, notably cancer. However, when it comes to infection diseases, the application of personalized medicine tools remains largely unexplored. Thanks to a groundbreaking scientific breakthrough, researchers at Tel Aviv University have set their sights on expanding the realm of personalized medicine to encompass infectious diseases as well. This newfound potential holds the promise of delivering more targeted and effective treatments to patients in need.
Until now, the medical world studied the immune response as a single unit, but a team of researchers at Tel Aviv University discovered a way, using experiments and computational tools, to classify two central components of the immune response that operate as a result of severe infectious disease. The importance of the discovery is that it provides a doorway to the world of personalized medicine in the field of infectious diseases and the provision of more effective treatments for patients. For example, instead of deciding to give a uniform medicine to all patients (i.e. an antibiotic like penicillin) the physician will be able to determine precisely which medicine he should give the patient and at what dosage, according to the classification of the infection based on analysis of the ratio between two key markers found in the patient’s blood.
Zooming in on the Immune System
The research was led by Prof. Irit Gat-Viks and Prof. Eran Bacharach, with the doctoral students Ofir Cohn and Gal Yankovitz from the Shmunis School of Biomedicine and Cancer Research in The George S. Wise Faculty of Life Sciences. The study was published in the prestigious journal, Cell Systems.
"From simple blood tests, we can learn a lot about the health status of people who became ill and give them more comprehensive treatment according to the development of the infection in their bodies." - Prof. Irit Gat-Viks
"In the general population, people react differently to infections, and therefore there is a need for medical tools to indicate how each person is expected to react to a certain infectious disease," explains Prof. Gat-Viks. She explains that, "until now, there have been only very general indicators to characterize these diseases, such as inflammatory markers, fever, urine tests, etc. Based on these indicators, analyses of the response to the infection that appeared rather uniform can be divided into different responses according to the new classification. In extreme cases, as we saw in the Corona epidemic, a person's immune response to the virus can result in lethality, and preliminary identification of their response can help us save lives. Our new observations and more precise classification of the inflammatory response has allowed us to identify new indicators and markers in our bloodstream. What all this means is that from simple blood tests, we can learn a lot about the health status of people who became ill and give them more comprehensive treatment according to the development of the infection in their bodies."
Prof. Eran Bacharach and Prof. Irit Gat-Viks
The researchers were able to observe the response of the immune system with high resolution, and identify two main types of responses. Prof. Bacharach outlines the first response as one in which, "the immune system fights a pathogen that has entered the body," and the other type and one in which "the damage to the body 'after the war' with the pathogen is repaired." In their research, they used disease models in animals, computational tools, and information collected from people with different markers in their bodies that are indicators of the type of response to the pathogen.
"People with extreme reactions to infection with microorganisms such as viruses or bacteria lack an adequate medical response today." - Prof. Irit Gat-Viks
Prof. Gat-Viks explains that "in fact, personalized medicine exists today for 'regular' diseases such as cancer, but there is almost no use of personalized medicine methods in the field of infectious diseases. People with extreme reactions to infection with microorganisms such as viruses or bacteria lack an adequate medical response today. We believe that thanks to our research, doctors will be able to better diagnose the patient's condition and, as a result, provide effective treatment that will improve the patient's chances of recovery. We aim to continue the research and discover more subgroups with different reactions among the population so that we can help doctors make their diagnosis more precise and thus provide proper treatment for their patients."
Advancing treatment and improving quality of life
Researchers at Tel Aviv University, among other institutions, have developed an innovative gene therapy that may help children suffering from Dravet syndrome (DS), a severe developmental epilepsy caused by a random mutation in the SCN1A gene during fetal development. DS is characterized by uncontrollable epilepsy, developmental delays, cognitive impairment, and a high risk of early death. The team's innovative gene therapy not only improved epilepsy but also protected against early death and enhanced cognitive abilities in DS lab models.
Breakthrough Gene Therapy
The researchers are hopeful that their genetic therapy can be adapted for other genetic epilepsies and may lead to the development of similar treatments for rare diseases. The study involved injecting a virus carrying a normal SCN1A gene into the brains of DS mice. The treatment demonstrated effectiveness in various critical aspects, even after the onset of severe epilepsy. The researchers express optimism that their laboratory technique will eventually reach clinical settings and provide help to children wit this debilitating disease. They also believe that the tools developed during this research will pave the way for similar treatments for other rare diseases.
The study was led by Dr. Moran Rubinstein and graduate student Saja Fadila, along with Anat Mavashov, Marina Brusel and Karen Anderson, all from the Sackler Faculty of Medicine and the Sagol School of Neuroscience at Tel Aviv University, and Dr. Eric Kremer, from the University of Montpellier in France. Also participating in the study were Bertrand Beucher and Iria González-Dopeso Reyes from Montpellier and other researchers from France, the USA and Spain. The research was published in the Journal of Clinical Investigation.
Dr. Moran Rubinstein
Dravet syndrome affects approximately one in 16,000 births and is considered relatively common among rare genetic diseases. Currently, there are around 70 affected children in Israel. The syndrome presents as thermally-induced seizures around six months of age, with progress to frequent spontaneous epileptic seizures and motor and cognitive developmental delays after one year.
Dr. Rubinstein highlights that existing epilepsy drugs are insufficient for children with DS, who face a significant risk of early death. The syndrome results from a genetic mutation that occurs randomly during fetal development in a gene called SCN1A and is not inherited from the parents. Unfortunately, the disease cannot be predicted or discovered during pregnancy, making early diagnosis challenging.
According to the researchers, it is customary nowadays to perform a genetic analysis for children who suffer from complex thermally-induced seizures around the age of six months. However, even if the test detects that the problem is in the SCN1A gene, the final diagnosis is often given after the epilepsy worsens, with the appearance of severe spontaneous convulsions and developmental delays. Although it is important to have an early diagnosis, diagnosis is often delayed, and most children are diagnosed only at the age of one or two years and sometimes even later.
Promising Results in Lab Models
Although genetic therapies have shown promise in DS mice and some of them are undergoing clinical trials in humans, they have only been effective when administered at very early stages, prior to symptom onset. Given the complex and invasive nature of gene therapy, it cannot be administered without a confirmed diagnosis of DS. Hence, the researchers focused on developing a treatment that could be effective after seizure onset, even at a relatively late age. Additionally, since DS involves cognitive impairments, the team aimed to alleviate both epilepsy and cognitive symptoms.
Dr. Rubinstein explains that viruses are commony used as carriers in genetic therapies to introduce normal genetic material into patients, enabling normal cellular function. For this purpose, the virus is engineered: its original genetic material is removed so it cannot cause disease or replicate itself, and instead, the relevant normal gene is packed inside. In the case of Dravet syndrome, since the SCN1A gene is very large, it was not possible to use common viruses that are usually used for this purpose and a virus capable of carrying and transferring large genes was needed. The team solved this problem by using a virus called Canine adeno virus type 2, as a carrier of the normal gene.
The carrier virus was directly injected into the brains of DS mice since its properties prevent it from crossing the blood-brain barrier. The treatment was administered to 31 mice at three weeks of age, after spontaneous convulsions had commenced (equivalent to one to two years of age in children), and to 13 mice at five weeks of age (equivalent to approximately six to eight years of age in children). The injection was performed in multiple brain areas, while an empty virus was injected into the brains of 48 control mice.
Potential for Rare Diseases
Promising results followed, with the highest efficacy observed when the treatment was administered at three weeks of age. In these mice, seizures ceased entirely within 60 hours of injection, life expectancy significantly increased, and cognitive impairment, assessed through spatial memory tests, was completely restored. Even in mice treated at five weeks of age, there was notable improvement, characterized by reduced epileptic activity and protection against thermally-induced seizures. In the control group that received the empty virus, no improvement was observed, and the mice experienced symptoms akin to untreated mice, with approximately 50% succumbing to early death due to severe epilepsy. The treatment was also applied to healthy mice without any adverse effects, demonstrating its safety.
The researchers clarify that their treatment restored normal function to damaged neurons in the brain by introducing a complete, normal gene. This approach is crucial in treating Dravet syndrome since the mutation can occur at different locations within the gene, and administering a complete gene provides a univform treatment suitable for all DS patients. Furthermore, the chosen virus infected numerous nerve cells and spread widely beyond the injection site, enhancing its effectiveness.
Dr. Rubinstein concludes that their treatment is the first proven to be effective for Dravet syndrome after the onset of spontaneous convulsions, offering improvement in cognitive function for DS mice. The team has already registered a patent, and hopes to see the treatment reach clinical settings to benefit children affected by this debilitating disease. They are also exploring its potential applicability to other genetic neurodevelopmental diseases. The developed platform represents a plug-and-play system for genetic therapies, with the possibility of incorporating different types of normal genetic material into the carrier virus for treating additional diseases in the future.
New study reveals critical insights in fight against skin cancer
A new study conducted at Tel Aviv University and the Sheba Medical Center reveals how melanoma cancer cells affect their close environment to support their needs - by forming new lymph vessels in the dermis to go deeper into the skin and spread through the body. The researchers believe that the new discovery may contribute to the development of a vaccine against the deadly cancer.
The Hidden Mechanism
The scientific breakthrough was led by Prof. Carmit Levy of Tel Aviv University's Sackler Faculty of Medicine and Prof. Shoshana Greenberger from the Sheba Medical Center. The study was funded by ICRF (the Israel Cancer Research Fund) and its results appeared in the Journal of Investigative Dermatology published by Nature.
"We demonstrated for the first time that in the first stage, in the epidermis, melanoma cells secrete extracellular vesiculas called melanosomes." - Prof. Shoshana Greenberger
The researchers (from left): Prof. Carmit Levy and Prof. Shoshana Greenberger
Melanoma, the deadliest of all skin tumors, starts with uncontrolled division of melanocyte cells in the epidermis – the top layer of the skin. In the second stage the cancer cells penetrate the dermis and metastasize through the lymphatic and blood systems.
In previous studies a dramatic rise was observed in the density of lymph vessels in the skin around the melanoma - a mechanism that was not understood by researchers until now.
"Our main research question was how melanoma impacts the formation of lymph vessels, through which it then metastasizes," explains Prof. Greenberger. "We demonstrated for the first time that in the first stage, in the epidermis, melanoma cells secrete extracellular vesiculas called melanosomes."
What are these vesiculas and how do they impact their environment? Examining this in human melanomas from the Pathology Institute, the researchers demonstrated that melanosomes could penetrate lymph vessels. They then examined their behavior in the environment of actual lymph vessel cells and found that here too the melanosomes penetrate the cells and give them a signal to replicate and migrate. In other words, the primary melanoma secretes extracellular vesiculas that penetrate lymph vessels and encourage the formation of more lymph vessels near the tumor, enabling the melanoma to advance to the lethal stage of metastasis.
"If we can stop the mechanisms that generate metastases in lymph nodes, we can also stop the disease from spreading" - Prof. Shoshana Greenberger
Melanoma's Stealth Tactics
Prof. Carmit Levy adds that, "melanoma cells secrete the extracellular vesiculas, termed melanosomes, before cancer cells reach the dermis layer of the skin. These vesicles modify the dermis environment to favor cancer cells. Therefore, melanoma cells are responsible for enriching the dermis with lymph vessels, thereby preparing the substrate for their own metastasis. We have several continuing studies underway, demonstrating that the melanosomes don't stop at the lymph cells, as they also impact the immune system, for example."
A Promising Vaccine Hope
Since melanoma is not dangerous at the premetastatic stage, understanding the mechanism by which the metastases spread via the lymphatic and blood systems can hopefully contribute to the development of a vaccine against this deadly cancer.
"Melanoma that remains on the skin is not dangerous," says Prof. Greenberger. "Therefore, the most promising direction for fighting melanoma is immunotherapy: developing a vaccine that will arouse the immune system to combat the melanosomes, and specifically to attack the lymphatic endothelial cells already invaded by the melanosomes. If we can stop the mechanisms that generate metastases in lymph nodes, we can also stop the disease from spreading."
CPAT, a groundbreaking Tel Aviv University development, offers promising results with sustained improvement months after treatment
Attention Deficit Hyperactivity disorder (ADHD) is one of the most common mental disorders affecting children. Symptoms of ADHD include inattention, hyperactivity, and impulsivity, and the disorder is considered a chronic and debilitating disorder that affects many aspects of an individual's life, including academic and professional achievements, interpersonal relationships, and daily functioning.
Tel Aviv University has developed a new treatment called Computerized Progressive Attention Training (CPAT), which has shown remarkable efficacy in alleviating symptoms of Attention Deficit Hyperactivity Disorder (ADHD) among students. In fact, a notable 33% of students experienced significant improvements in their symptoms when undergoing CPAT, surpassing the improvement in symptoms of only 11% of the students who participated in a parallel protocol involving mindfulness training. During this mindfulness training, students practiced a specific form of meditation designed to mitigate their attention difficulties. Importantly, the benefits of CPAT also outshone those of drug treatments like Ritalin, as the improvements persisted for up to four months after the completion of the treatment protocol.
Research Challenges with Non-Medication Interventions
The study was the doctoral dissertation of Dr. Pnina Stern, under the guidance of Prof. Lilach Shalev-Mevorach of The Jaime and Joan Constantiner School of Education at Tel Aviv University. The encouraging results of the study were recently accepted for publication in the Journal of Attention Disorders.
“We developed the CPAT system years ago, and it produced good results in previous studies that we conducted, mainly in children," explains Prof. Shalev-Mevorach. "Furthermore, in the only study that we conducted in adults with ADHD, positive findings were obtained, but without indications of ‘far transfer,’ meaning an improvement in functions for which participants were not directly trained in the treatment.”
According to Prof. Shalev-Mevorach, it is challenging for researchers to make scientific claims about the effectiveness of non-medication treatments because it is difficult to compare them to a "non-medication placebo." In other words, when studying non-medication treatments, it's hard to distinguish the effects of the treatment itself from other factors like the attention participants receive during training sessions or the effort they put into the research. This makes it complex to determine the true impact of non-medication interventions.
Prof. Lilach Shalev-Mevorach
Students with ADHD Enrolled
In the current study, the team of researchers tried to resolve this by employing a research design that included two control groups: a regular control group, which performed the various assessment tasks at two points in time without any intervention as part of the research (the passive control group) and a second control group that participated in mindfulness training sessions under the guidance of a professional instructor. This type of training has yielded positive results in previous studies in people with ADHD.
For the experiment 54 students, male and female, diagnosed with ADHD were recruited from Tel Aviv University and other academic institutions. The subjects were blindly divided into three groups: a zero-intervention control group, a mindfulness group and a CPAT group.
Participants in the CPAT and the Mindfulness groups attended two-hour long group meetings on the University campus once a week, where the CPAT group received Computerized Progressive Attention Training and the mindfulness group received training from a certified mindfulness instructor.
Before and after the intervention protocol, the participants of the three groups performed a comprehensive series of assessment tests: standard computerized tests to assess attention functions, behavioral assessment questionnaires (self-reported ADHD symptoms), and mindfulness questionnaires (self-reported feelings such as stress, anxiety and well-being). In addition, a novel measurement was used for this intervention study, whose participants were, as mentioned, higher-education students: they were asked to read a text from a scientific article while their eye movements were tracked by an eye-tracker. The indices produced using the eye-tracking system made it possible to identify a pattern of inattentive reading, which was used as a measure of reading efficiency in an academic context. Finally, the participants filled out a questionnaire regarding their academic difficulties.
Improvements Maintained Over Time
Prof. Shalev-Mevorach says the results were very positive: “We saw improvements in the attention functions themselves, that is, ‘near transfer,’ for example in sustained attention, the ability to remain attentive for a long period of time, and in attention control, the ability to delay a routine response. But the main thing, is that we saw significant improvements in the participants’ daily and academic functioning, such as reduced repeated reading while reading a scientific article. Furthermore, the improvements in these attention functions were connected to the reduction in behavioral symptoms of ADHD and in repetitive reading."
"In other words, the CPAT trained the attention mechanisms themselves, and their improvement was related to the improvement achieved in behavioral symptoms and reading patterns. 33% of the participants who received the CPAT protocol showed a significant improvement in ADHD symptoms, compared to only 11% of those who underwent the mindfulness protocol. The improvements obtained were preserved in the testing that was carried out about four months after the end of the intervention protocol.”
Prof. Shalev-Mevorach notes that the effects of stimulant drugs (psychostimulants) such as Ritalin and Concerta are ‘on-off’: patients who take Ritalin daily enjoy significant improvements, but when they stop the treatment, the improvements fade, and they return to the starting point. She says the researchers wish to bring about "a profound change in basic attention functions, a change that will be significant in the long term, as an additional option alongside medication, and of course as an alternative to drug treatment in cases in which it isn’t applicable.”
The role of hope in supporting mental health
The role of hope in supporting mental health is not sufficiently understood among relevant professionals, according to Dr. Dorit Redlich Amirav of TAU’s Department of Occupational Therapy, Steyer School of Health Professions, Sackler Faculty of Medicine.
“Hope is similar to the air we breathe,” says Redlich Amirav. “Air is taken for granted in our daily life until we are suffocating and struggling to breathe.”
How Hope Transcends Generations
Redlich Amirav studies how different groups implement hopeful thinking and improve mental well-being through meaningful occupations. Through her findings, she aspires to help mental health professionals to integrate concepts of hope into their research and treatment and, in the long run, provide a longer-lasting and greater impact on each patient’s holistic well-being.
"Hope is similar to the air we breathe. Air is taken for granted in our daily life until we are suffocating and struggling to breathe." - Dr. Dorit Redlich Amirav
In new research published in Qualitative Health Research, she investigated the cross-generational transmission of hope. Redlich Amirav cites one of her female participants who was forced by her grandfather to quit school in sixth grade. She felt her hope diminish but stated that her hopeless personal circumstances led her to put more of an emphasis on the importance of education and studying with her own two daughters who both graduated from university.
Other participants displayed this particular kind of cross-generational hope. For example, a mother told Redlich Amirav about her father, who was a violinist until the Nazis broke his fingers. The mother internalized this trauma in a negative way, but all four of her own children play instruments and one of them is an opera singer. She inadvertently conveyed how hope and music are intertwined for them and their heritage.
Hope as a Key to Pandemic Adaptation
In 2019, Redlich Amirav was appointed director of the Israeli chapter of the International Hope Barometer. She says that it came just in time: hope became a key factor in successfully adapting to the trials and tribulations of the pandemic. During the lockdowns, she says that people found meaning in new ways of interacting; specific trends point to the importance of goal-directed behavior in increasing hope.
Source: TAU Review
New study reveals that brain's coordination between hippocampus and cortex during sleep boosts memory consolidation, offering hope for people with memory impairments
While a good night's sleep is known to be critical for the consolidation of long-lasting memories, so far there has been little evidence regarding the precise processes at work during human sleep. A breakthrough study demonstrated for the first time that long-lasting memories are consolidated in the human brain through communication between the hippocampus and the cerebral cortex during sleep. Moreover, the researchers found that by inducing deep-brain stimulation during sleep they can improve memory consolidation. They believe intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia.
Enhancing Memory Consolidation During Sleep
The unique study, which was published in the leading journal Nature Neuroscience, involved an international collaboration led by Dr. Maya Geva-Sagiv (today at UC Davis). The study was a collaboration between the laboratories of Prof. Yuval Nir from the Sackler Faculty of Medicine, Department of Biomedical Engineering at The Iby and Aladar Fleischman Faculty of Engineering, and Sagol School of Neuroscience at Tel Aviv University, and Prof. Itzhak Fried from the Department of Neurosurgery at UCLA and the Sackler Faculty of Medicine at Tel Aviv University.
"Intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia." - Prof. Yuval Nir
The researchers (from left to right): Dr. Maya Geva-Sagiv, Prof. Yuval Nir and Prof. Itzhak Fried
"This study was made possible by a rare group of 18 patients with epilepsy at the UCLA Medical Center," says Prof. Nir. "Prof. Fried implanted electrodes in these patients' brains to try and pinpoint the areas that cause their epileptic seizures, and they volunteered to take part in a study investigating the effects of deep-brain stimulation during sleep. Close work with expert neurologists led by Prof. Dawn Eliashiv at UCLA enabled our team to integrate advanced brain stimulation in the research. Thus, we were able to test, for the first time in humans, the long-held hypothesis - that coordinated activity of the hippocampus and cerebral cortex during sleep is a critical mechanism in consolidating memories."
"Moreover, we improved memory consolidation through a special stimulation protocol that enhanced synchronization between these two areas in the brain. Intervention during sleep represents a unique approach that can be further developed in the future to provide hope for people with memory impairments such as dementia."
"In this study we directly examined the role of neural activity and electrical brain waves during sleep. Our goal was to enhance the natural mechanisms at play, to discover exactly how sleep assists in stabilizing memories." – Dr. Maya Geva-Sagiv
"We know that a good night's sleep is critical for the consolidation of long-lasting memories, but so far, we had little evidence regarding the precise processes that are at work during human sleep," explains Dr. Maya Geva-Sagiv. "In this study we directly examined the role of neural activity and electrical brain waves during sleep. Our goal was to enhance the natural mechanisms at play, to discover exactly how sleep assists in stabilizing memories."
The researchers developed a deep-brain stimulation system that improves electrical communication between the hippocampus – a deep-brain region involved in acquiring new memories, and the frontal cortex – where memories are stored for the long term. By monitoring activity in the hippocampus during sleep, the system enables precisely timed delivery of electrical stimulation to the frontal cortex.
The study's participants completed two memory tests, and their performance was compared after two different nights – one undisturbed and one with deep-brain stimulation. On both occasions, they were asked in the morning to recognize famous persons whose pictures they had been shown the previous evening. The study found that deep-brain stimulation significantly improved the accuracy of their memory.
"To our surprise, we also discovered that the intervention did not significantly increase the number of right answers given by participants, but rather reduced the number of wrong answers. This suggests that sleep sharpens the accuracy of our memory…" - Prof. Yuval Nir
Sharpening Memory Accuracy
"We found that our method had a beneficial effect on both brain activity during sleep and memory performance," says Prof. Fried. "All patients who had received synchronized stimuli to the frontal cortex demonstrated better memory performance, compared to nights of undisturbed sleep. The control group, which received similar yet unsynchronized stimuli, showed no memory improvement. Our deep-brain stimulation method is unique because it is close-looped – stimuli are precisely synchronized with hippocampal activity. In addition, we monitored the stimuli's impact on brain activity at a resolution of individual neurons."
"Our findings support the hypothesis that precise coordination between sleep waves assists communication between the hippocampus that takes in new memories, and the frontal cortex that stores them for the long term," adds Prof. Nir.
"To our surprise, we also discovered that the intervention did not significantly increase the number of right answers given by participants, but rather reduced the number of wrong answers. This suggests that sleep sharpens the accuracy of our memory, or in other words, it removes various distractions from the relevant memory trace."
The study was supported by grants from the US National Institutes of Health (NIH), the European Research Council (ERC), the US National Science Foundation (NSF), the US-Israel Bilateral Science Foundation (BSF), and the Human Frontier Science Program (HFSP). The paper’s other co-authors are: Prof. Dawn Eliashiv, Dr. Emily Mankin, Natalie Cherry, Guldamla Kalender, and Dr. Natalia Tchemondanov of UCLA, and Dr. Shdema Epstein from Tel Aviv University.
Breakthrough method revolutionizes agricultural crop improvement for enhanced properties
- Life Sciences
Since the agricultural revolution, mankind has strived to enhance plant varieties through genetic diversity. However, until recently, our understanding was limited to the functions of individual genes, which account for just 20% of the genome. The remaining 80%, comprised of genes grouped in families, remained a mystery on a large genomic scale.
In a groundbreaking achievement, Tel Aviv University researchers have harnessed the power of CRISPR technology to develop an innovative and scalable genetic modification method. This breakthrough allows us to uncover the roles and characteristics of duplicated genes in plants. As a result, the team has successfully identified numerous overlooked features, paving the way for a revolutionary approach to crop improvement. This remarkable development has the potential to revolutionize agricultural practices across a wide range of crops and traits, including increased yields and enhanced resistance to drought and pests.
Overcoming Genetic Redundancy
This groundbreaking research was led by postdoctoral student Dr. Yangjie Hu, under the guidance of Prof. Eilon Shani and Prof. Itay Mayrose from the School of Plant Sciences and Food Security at TAU's The George S. Wise Faculty of Life Sciences. Collaborating with scientists from France, Denmark, and Switzerland, the team utilized the CRISPR gene editing technology along with bioinformatics and molecular genetics methods to develop this novel gene-location method. The research was published in the prestigious journal Nature Plants.
"We wanted to apply this technique to improve the control of creating mutations in plants for the purposes of agricultural improvement, and specifically to overcome the common limitation posed by genetic redundancy." – Prof. Itay Mayrose
Genetic redundancy, caused by gene families, has long posed a challenge in plant research. Previous methods of genetic intervention were limited by the inability to precisely identify genes responsible for specific traits. The accepted method to address this challenge is to produce mutations, that is, to modify genes in different ways, and then to examine changes in the plant’s traits as a result of the mutation in the DNA and to learn from this about the function of the gene.
Thus, for example, if a plant with sweeter fruit develops, it can be concluded that the altered gene determines the sweetness of the fruit. This strategy has been used for decades, and has been very successful, but it also has a fundamental problem: an average plant such as tomato or rice has about 30,000 genes, but about 80% of them do not work alone but are grouped in families of similar genes. Therefore, if a single gene from a certain gene family is mutated, there is a high probability that another gene from the same family (actually a copy very similar to the mutated gene) will mask the phenotypes in place of the mutated gene. Due to this phenomenon, called genetic redundancy, it is difficult to create a change in the plant itself, and to determine the function of the gene and its link to a specific trait.
The research team
The team addressed this challenge by using CRISPR and designing sgRNA sequences that guide an enzyme called Cas9 found naturally in bacteria to cut specific genetic sequences associated with entire gene families. Prof. Mayrose explains that "this genetic editing method allows us to design different sgRNA sequences to allow Cas9 to cut almost any gene that we want to change. We wanted to apply this technique to improve the control of creating mutations in plants for the purposes of agricultural improvement, and specifically to overcome the common limitation posed by genetic redundancy."
In the first stage, a bioinformatics study was carried out on a computer, which, unlike most studies in the field, initially covered the entire genome. The researchers chose to focus on the Arabidopsis plant, which is used as a model in many studies and has about 30,000 genes. First, they identified and isolated about 8,000 individual genes, which have no family members, and therefore no copies in the genome. The remaining 22,000 genes were divided into families, and for each family appropriate sgRNA sequences were computationally designed. Each sgRNA sequence was designed to guide the Cas9 cutting enzyme to a specific genetic sequence that characterizes the entire family, with the aim of creating mutations in all family members so that these genes can no longer overlap each other. In this way, a library was built that totaled approximately 59,000 sgRNA sequences, where each sgRNA by itself can simultaneously modify 2-10 genes at once from each gene family, thereby effectively neutralizing the phenomenon of genetic redundancy.
In addition, the sgRNA sequences were divided into ten sub libraries of approximately 6,000 sgRNA sequences each, according to the presumed role of the genes – such as coding for enzymes, receptors, transcription factors, etc. According to the researchers, establishing the libraries allowed them to focus and optimize the search for genes responsible for desired traits, a search that until now has been largely random.
"We believe that this is the future of agriculture: controlled and targeted crop improvement on a large scale. Today, we are applying the method we developed to rice and tomato plants with great success, and we intend to apply it to other crops as well." – Prof. Eilon Shani
In the next step, the researchers moved from the computer to the laboratory. Here they generated all 59,000 sgRNA sequences designed by the computational method and engineered them into new plasmid libraries (i.e., circular DNA segments) in combination with the cutting enzyme. The researchers then generated thousands of new plants containing the libraries - where each plant was implanted with a single sgRNA sequence directed against a specific gene family.
The researchers observed the traits that were manifested in the plants following the genome modifications, and when an interesting phenotype was observed in a particular plant, it was easy to know which genes were responsible for the change based on the sgRNA sequence that was inserted into it. Also, through DNA sequencing of the identified genes, it was possible to determine the nature of the mutation that caused the change and its contribution to the plant's new properties.
In this way, many new traits were mapped that until now were blocked due to genetic redundancy. Specifically, the researchers identified specific proteins that comprise a mechanism related to the transport of the hormone cytokinin, which is essential for optimal plant development.
Commercialization and Future Impact
Prof. Shani concludes: "The new method we developed is expected to be of great help to basic research in understanding processes in plants, but beyond that, it has enormous significance for agriculture: it makes it possible to efficiently and accurately reveal the pool of genes responsible for traits we seek to improve - such as resistance to drought, pests, and diseases, or increasing yields. We believe that this is the future of agriculture: controlled and targeted crop improvement on a large scale. Today we are applying the method we developed to rice and tomato plants with great success, and we intend to apply it to other crops as well."
Recognizing the transformative potential of this breakthrough, Tel Aviv University's technology commercialization company, Ramot, partnered with the AgChimedes group to establish DisTree, a company dedicated to applying this technology to different crops. This collaboration, along with financial investment and professional support, aims to revolutionize agricultural genetics and ensure nutritional security in the face of climate crises.
Deadly epidemic killed all the black sea urchins in the Gulf of Eilat, placing coral reefs at risk
- Life Sciences
Recent, unsettling studies conducted by Tel Aviv University have unveiled a deadly epidemic responsible for the widespread decimation of black sea urchins in the Mediterranean Sea and the Gulf of Eilat. Over the span of just a few months, the entire population of black sea urchins in Eilat was eradicated. For instance, within a few weeks, thousands of sea urchins inhabiting a site near the northern shore of the Gulf of Eilat perished. The severity of the epidemic is such that only skeletal remains of black urchins now occupy the site. Disturbingly, similar occurrences have been observed at various other locations in the Gulf of Eilat, as well as in neighboring countries including Jordan, Egypt, Saudi Arabia, Greece, and Turkey.
"At first we thought it was some kind of pollution or poisoning, or a local chemical spill (…) but when we examined additional sites in Eilat, Jordan, and Sinai, we quickly realized that this was not a local incident. All findings pointed to a rapidly spreading epidemic." - Dr. Omri Bronstein.
Unveiling Deadly Epidemic
The studies were led by Dr. Omri Bronstein and PhD students Rotem Zirler, Lisa-Maria Schmidt, Gal Eviatar, and Lachan Roth from the School of Zoology, at The George S. Wise Faculty of Life Sciences, and The Steinhardt Museum of Natural History at Tel Aviv University. The papers were published in Frontiers in Marine science and Royal Society Open Science.
The researchers underscore the vital importance of sea urchins, particularly the long-spined Diadema setosum, as keystone species essential for the thriving equilibrium of coral reefs. They express a pressing concern, stating, "It must be understood that the threat to coral reefs is already at an all-time peak, and now a previously unknown variable has been added. This situation is unprecedented in the documented history of the Gulf of Eilat."
According to the researchers' hypothesis, the cause of the deadly epidemic can be attributed to a pathogenic ciliate parasite that has spread from the Mediterranean to the Red Sea. In response to the gravity of the situation, an urgent report outlining the current state has been submitted to the Israel Nature and Parks Authority, instigating deliberation on emergency measures to safeguard Israel's coral reefs.
"Sea urchins in general, and Diadema setosum in particular, are considered key species essential for the healthy functioning of coral reefs. The sea urchins are the reef's 'gardeners' – they feed on the algae and prevent them from taking over and suffocating the corals that compete with them for sunlight." – Dr. Omri Bronstein
Dr. Omri Bronstein and a dying sea urchin
"At first we thought it was some kind of pollution or poisoning, or a local chemical spill, from the industry and hotels in the north of the Gulf of Eilat, but when we examined additional sites in Eilat, Jordan, and Sinai, we quickly realized that this was not a local incident," explains Dr. Bronstein. "All findings pointed to a rapidly spreading epidemic. Similar reports are coming in from colleagues in Saudi Arabia. Even sea urchins that we grow for research purposes in our aquariums at the Interuniversity Institute, and sea urchins at the Underwater Observatory Marine Park in Eilat, contracted the disease and died, probably because the pathogen got in through the pumping systems."
Dr. Bronstein describes it as a fast and violent death: "Within just two days a healthy sea urchin becomes a skeleton with massive tissue loss. While some corpses are washed ashore, most sea urchins are devoured while they are dying and unable to defend themselves, which could speed up contagion by the fish who prey on them."
Invasion and Vanishing Species
In recent years, Dr. Bronstein's research group has dedicated their efforts to the investigation of marine invasions, with a specific focus on the long-spined Diadema setosum. "Until recently, the black sea urchins with long spines, familiar to many of us, was one of the dominant species in Eilat's coral reef," reflects Dr. Bronstein. "Sea urchins in general, and Diadema setosum in particular, are considered key species essential for the healthy functioning of coral reefs. The sea urchins are the reef's 'gardeners' – they feed on the algae and prevent them from taking over and suffocating the corals that compete with them for sunlight. Regrettably, these once-thriving sea urchins have vanished from the Gulf of Eilat and are quickly disappearing from constantly expanding parts of the Red Sea further to the south," shares Dr. Bronstein with a sense of lament.
A dying urchin in the Mediterranean Sea (photo: Dr. Omri Bronstein)
Several months ago, Dr. Bronstein was alerted to the initial reports of widespread mortality by colleagues in Greece and Turkey, where the sea urchins had invaded, likely via the Suez Canal. "In 2006, the first sighting of this species of sea urchin occurred in the southern regions of Turkey," Dr. Bronstein adds. This phenomenon, known as biological invasion, carries far-reaching ecological implications, pervasively affecting the eastern Mediterranean, particularly along Israel's coastline. "We have been monitoring the dynamics of this species' invasion in the Mediterranean since its first emergence," he shares.
In 2016, they discovered the first Diadema setosum sea urchin along Israel’s Mediterranean coastline – a lone urchin sighted at Gordon Beach in Tel Aviv. For over a decade since the first discovery in Turkey, the Mediterranean populations of these sea urchins remained small and usually hidden. However, since 2018 the sea urchin population in the Mediterranean has been growing exponentially, reaching a state of population explosion – with giant populations of thousands and even tens of thousands found in Greece and Turkey.
"The window of opportunity for preserving a thriving population of this species in Eilat has regrettably closed. To establish a safeguard population, we must act without delay, by preserving healthy individuals from the Israeli Mediterranean before the encroaching disease from the north reaches this region." Dr. Omri Bronstein
"However, during the course of our research, while scrutinizing the invasion of sea urchins in the Mediterranean, we began to receive reports on sudden extensive mortality," says Dr. Bronstein. "While the extinction of an invasive species is supposedly not a bad thing, we must be aware of two major risks: Firstly, we don't yet know how this mortality and its causes might impact local species in the Mediterranean. Secondly, and of far greater significance, the geographic proximity shared by the eastern Mediterranean and the Red Sea provides a potential conduit for the swift transmission of the pathogen into the Red Sea. As we feared and predicted, this is what appears to have happened."
Dr. Bronstein and his research team (photo: courtesy of Dr. Omri Bronstein)
A Reminiscent Crisis
The massive loss of sea urchins reminded the TAU researchers of one of the most devastating events in marine ecology: the disappearance of the sea urchins in the Caribbean. Until 1983, the Caribbean coral reef thrived as a vibrant tropical ecosystem, much like the one in the Gulf of Eilat. But as the sea urchins vanished, the uncontrollable growth of algae took over, blocking sunlight from reaching the corals and forever altering the reef into a sea of algae.
Dr. Bronstein reveals, "Just last year, the Caribbean experienced another outbreak of the disease, resulting in the demise of the remaining urchin populations. However, unlike previous incidents, we now possess advanced scientific and technological resources to analyze the forensic evidence. Researchers from Cornell University successfully pinpointed the cause of mortality in the Caribbean: a pathogenic ciliate parasite. The identical pathology observed in the dying sea urchins of Greece, Turkey, and the Red Sea corroborates this finding."
Dr. Bronstein's pioneering research not only identified the unprecedented mass mortality of an invasive species in the Mediterranean but also shed light on the alarming decline of the widely prevalent sea urchin species, Diadema setosum. In a groundbreaking study, Dr. Bronstein issued a a warning that the epidemic plaguing the Mediterranean could extend its reach to the nearby Red Sea. Sadly, this cautionary prediction has become a disheartening reality.
Urgent Measures and Closing Window
"The gravity of the situation cannot be understated: the Red Sea is witnessing an alarming surge in mortality, surpassing the extent observed in the Mediterranean. Looming in the background is an ominous uncertainty: What is the exact cause of the sea urchin die-offs? Is it the same Caribbean pathogen or an entirely new and unfamiliar factor? Regardless, it is evident that this pathogen spreads through water, and we anticipate a rapid escalation of sickness and demise among the entire population of these sea urchins in both the Mediterranean and the Red Sea."
"In my view, it is imperative that we swiftly establish a safeguard population for these sea urchins, ensuring the potential for their reintroduction into the wild. Similar to the approach taken with COVID-19, the trajectory of this epidemic remains uncertain. Will it eventually subside on its own, or persist for years, radically transforming coral reefs? However, unlike the COVID-19 pandemic, there are no available vaccines or treatments for the afflicted sea urchins. Hence, our efforts must be steadfastly directed towards prevention. The window of opportunity for preserving a thriving population of this species in Eilat has regrettably closed. To establish a safeguard population, we must act without delay, by preserving healthy individuals from the Israeli Mediterranean before the encroaching disease from the north reaches this region. While this is a complex undertaking, it is imperative if we aspire to secure the future of this unique species, which plays a critical role in the destiny of coral reefs," concludes Dr. Bronstein.
Researchers trace continuity in Israel's local wine industry from the Byzantine period to the present day
- Life Sciences
A new study led by the paleogenetic laboratory of the Steinhardt Museum of Natural History at Tel Aviv University and the University of Haifa analyzed DNA from ancient local winegrape seeds discovered at archaeological excavations in the Negev. One seed was found to be almost identical to the Syriki variety used today to make high-quality red wine in Greece and Lebanon, while another seed is a relative of the white variety called Be'er, still growing in deserted vineyards in the dunes of Palmachim.
Exported to Europe
The genetic study was led by Dr. Pnina Cohen and Dr. Meirav Meiri of the paleogenetic lab at the Steinhardt Museum of Natural History at Tel Aviv University. The seeds were found at archaeological excavations led by Prof. Guy Bar-Oz from the School of Archaeology and Maritime Cultures at the University of Haifa, in collaboration with researchers from the Israel Antiquities Authority. Other participants included researchers from the University of Haifa, the Weizmann Institute, Bar-Ilan University, and research institutions in France, Denmark, and the UK. The paper was published in the leading scientific journal PNAS.
"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine." - Prof. Guy Bar-Oz
"Archaeological excavations conducted in the Negev [in Israel] in recent years have revealed a flourishing wine industry from the Byzantine and early Arab periods (around the fourth to ninth centuries A.D.), especially at the sites of Shivta, Haluza, Avdat, and Nizana, which were large, thriving cities at the time," says Prof. Guy Bar-Oz from the University of Haifa.
"The findings include large winepresses, jugs in which the exclusive wine, exported to Europe, was stored, and grape seeds preserved for more than a thousand years. This industry gradually declined following the Muslim conquest in the 7th century, since Islam forbids the consumption of wine."
"The cultivation of winegrapes in the Negev was renewed only in modern times, in the state of Israel, mostly since the 1980s. This industry, however, relies mainly on winegrape varieties imported from Europe."
Avdat Excavation (photo: Tali. Erickson-Gini and Scott Bucking)
One especially interesting finding was a large hoard of grape seeds, discovered on the floor of a sealed room at Avdat. The researchers explain that these seeds have been relatively well preserved thanks to protection from climatic phenomena such as extreme temperatures, flooding, or dehydration. To learn more about the seeds, in the hope of discovering which varieties they might belong to, the researchers prepared to extract their DNA in the paleogenetic lab.
"The science of paleogenomic uses a range of advanced technologies to analyze ancient genomes, primarily from archaeological findings," explains Dr. Meiri from the Steinhardt Museum of Natural History at Tel Aviv University. "Since the DNA molecule is very sensitive and disintegrates over time, especially under high temperatures, we usually get only small pieces of DNA, often in a poor state of preservation. To protect them we work under special conditions: the paleogenetic lab is an isolated clean laboratory, with positive air pressure that keeps contaminants out, and we enter it in sterilized 'spacesuits' familiar to everyone from the COVID pandemic."
To begin with, the researchers looked for any organic matter remaining in the seeds. For this purpose, they used FTIR (Fourier-transform infrared spectroscopy) – a chemical technique applying infrared radiation to produce a light spectrum that identifies the sample's content. Finding remnants of organic matter in 16 seeds, the researchers went on to extract DNA from these samples.
Ancient local winegrape seeds from Shivta, Israel (photo: Prof. Guy Bar-Oz, The University of Haifa)
Ancient Grapes - Still Around Today
The extracted DNA was sequenced, with an emphasis on about 10,000 genomic sites where variety-specific features are usually found, and the results were compared to databases of modern grapevines from around the world: In 11 samples, the quality of genetic material was too poor to allow any definite conclusions. Three of the remaining samples were identified as generally belonging to local varieties. Finally, the two samples of the highest quality, both from around 900 A.D., were identified as belonging to specific local varieties that still exist today.
The discovery was quite extraordinary:
- One seed was found to belong to Syriki, a known Middle Eastern variety with a long history of cultivation in the Southern Levant and Crete, still used today to make high-quality red wine in Greece (where it is known to have arrived from the east) and in Lebanon. Since winegrapes are usually named after their place of origin, it is quite possible that the name Syriki is derived from Nahal Sorek, an important stream in the Judean Hills. Moreover, this variety may even appear in the Bible – in Jacob's blessing to his son Judah: "He will tether his donkey to a vine, his colt to the choicest branch (soreka); he will wash his garments in wine, his robes in the blood of grapes (Genesis 49, 11); and perhaps also suggested in the giant cluster of grapes brought back by the men sent by Moses to explore the land: "When they reached the Valley of Eshkol (identified by some as Nahal Sorek), they cut off a branch bearing a single cluster of grapes. Two of them carried it on a pole between them" (Numbers 13, 23).
- The other high-quality seed was identified as related to Be'er, a white winegrape variety still growing in the sands of Palmachim on Israel's seashore, in remnants of vineyards probably abandoned in the mid- 20th century. For the first time ever, the researchers were able to use the genome of a grape seed to determine the color of the fruit, discovering that it was in fact a white grape - the oldest botanical specimen of a white variety ever identified. Be'er, a unique local variety, endemic to the land of Israel, is used today by the Barkan winery to make a special white wine of its own.
"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story. This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day." - Dr. Meirav Meiri
Tiny Items Tell a Big Story
"The wonderful thing about paleogenetics is that sometimes, tiny items can tell a big story," says Dr. Meiri. "This is exactly what happened in this study. With just a bit of DNA extracted from two grape seeds we were able to trace continuity in the local wine industry - from the Byzantine period, more than a thousand years ago, to the present day."
"We believe that our findings are also significant for Israel's modern wine industry, which has been growing and thriving in recent decades. Today, most varieties grown here have been imported from Europe, so that the local conditions are not optimal for them. Local varieties can be more suitable for the local climate and soil, especially in the desert region of the Negev. Our study opens new paths for restoring and improving ancient local varieties, to create winegrapes that are more suitable for challenging climatic conditions such as high temperatures and little rainfall."
Tiny items can tell a big story. Ancient winegrape seeds under a Microscope from Avdat (photo: Prof. Guy Bar-Oz, The University of Haifa)
Using RNA-based nanodrugs the researchers achieve 80% survival rate in lab models
- Life Sciences
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."
New study finds that pregnancy affects bats' sensing capabilities
- Life Sciences
"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.”