16 research proposals were selected in the second round of the research program in personalized medicine of the National Science Foundation

The total amount of research grants in the current round of submissions is approximately 60 million shekels * The total scope of grants for the first two rounds is approximately 120 million shekels * The research program is based on a pooling of resources in which the Planning and Budgeting Committee of the Council for Higher Education, the Ministry of Health, the Ministry's Digital Israel initiative take part for social equality, Yad Hanadiv and the Kellerman Family Foundation (Boston) * The RMA program is managed and operated by the National Science Foundation

The research in the field of personalized medicine is based on extensive interdisciplinary collaborations, which combine scientific and medical knowledge, theory, in-depth analyzes of huge medical data and extensive experimental work. The winning studies used information found in tissue repositories and the unique databases of the health institutions in Israel, while strictly maintaining the privacy of the patients. It should be noted that Israel has a huge comparative advantage in the field in light of the extensive scope and high reliability of these databases.

The international judging team headed by Nobel Prize laureate in chemistry, Prof. Roger Kornberg from a university Stanford Choose, after a thorough examination the 16 The leading research proposals in the second cycle of the Rama program, which will be awarded research grants in the total amount of approx. 60 million shekels. Rama is a new research program - the first of its kind in Israel, which was launched about two years ago (summer 2018) with a total budget of approx 210 million shekels,  The program will be operated in four submission cycles. The duration of each study will be up to 4 Years.

Prof. Yuval Dor, chairman of the field of biology and medicine at the National Science Foundation: "In the second cycle of the program for personalized medicine, we once again witnessed an abundance of excellent research programs that reflected the scientific depth and the spirit of cooperation between researchers and doctors in Israel and between universities, hospitals and health insurance funds. We are happy that we were able to maintain the competitive judging process in order despite the disruptions caused by the Corona epidemic. The winning proposals come from a variety of universities and medical institutions, deal with essential questions for human health and are expected to lead to important scientific insights and medical applications."

Prof. Yaffe Zilbrashch, chairman of the Faculty of Science and Technology: "The Rama program is a source of pride and satisfaction. At the end of the first cycle, it was clear that the program succeeded beyond expectations. The second cycle reinforces this understanding. I am excited to see the contents of the winning grants, their scientific quality and the collaborations between researchers from the Academy of Physicians and researchers from the health organizations. There is no doubt that the program will make a tremendous contribution to the advancement of research and medicine in Israel and around the world. I thank from the bottom of my heart the people of the National Science Foundation who met the challenging task of judging the proposals within the timetables despite the Corona epidemic".

Shi-Lee Spiegelman, Head of Digital Israel Headquarters: The research program in personalized medicine is a significant part of the digital health initiative as a growth engine, placing Israel at the forefront of the digital health revolution. This program demonstrates the enormous value of the medical information created in Israel. The excellent studies won in the second cycle of the program will deepen the human understanding of a variety of diseases, and will help in their prevention and treatment. Just as importantly, they will strengthen the existing excellent cooperation between the academy and the Israeli health system. This cooperation is at the foundation of Israeli excellence in health, and is one of the reasons why Israel successfully weathered the first wave of the Corona epidemic.

Background on the RMA program and its essence:

The RMA (personalized medicine) program focuses on a deep understanding of the differences and mechanisms responsible for the variations in the characteristics of the same disease in different patients and works to promote innovative, ground-breaking research that will lead to a deep understanding of human biology and the mechanisms involved in human diseases. Many studies, carried out over the past few years, indicate that people who are sick with the same disease (for example: diabetes, various types of leukemia, breast cancer, Crohn's disease, etc.) may develop a different manifestation of the disease, including - a different rate of development of the disease, differences in the severity of the disease , and variation in response to treatment.

The existence of considerable variation between patients has been recognized in the world of medicine for a long time, but the understanding of the reasons that cause this variation is still limited. In the absence of established information on the causes of this variation, it is more difficult to optimally adapt treatment to the disease for each and every patient.

The RMA program is designed to deal with these challenges, using a wide variety of technologies, activating multidisciplinary research teams, including doctors, basic researchers, theorists, experimentalists, computational biologists, computer science and data scientists, engineers, statisticians, epidemiologists, and more.

The partners in financing the program: The Planning and Budgeting Committee of the Council for Higher Education (VAT), משרד הבריאות, project Digital Israel in the Ministry of Social Equality and two philanthropic foundations: Keren the benevolent hand In Israel and the Kellerman Family Foundation in the USA. The program is operated and managed by National Science Foundation.

The program will allow Israeli researchers to promote wide-ranging research in the fields of human health, based on extensive collaborations between researchers in higher education institutions and medical institutions in Israel, on populations of healthy and sick volunteers, as well as on the basis of huge data (big data) found in the databases of hospitals and health insurance funds in Israel.

The collaborations between the researchers at the universities and the health institutions significantly advance the research capabilities in the field in Israel, help accelerate the pace of discoveries and the potential for the application of new therapeutic approaches, while positioning Israel as a pioneer at the forefront of global science in the field of personalized medicine.

In September 2019 The second call for research in the field was published, submitted 75 Research proposals, which are based on collaborations of extraordinary scope, and include a wide variety of subjects in the fields of human medicine. The applications went through an in-depth judging process by international experts, from which they were selected 16 Applications for funding.

in September 2020 It is expected that another call will be published for the third cycle out of the four planned cycles.

It should be noted that due to the Corona epidemic, an additional grant program was approved in April 2020, which is intended for the rapid funding of targeted research to curb the disease Covid-19. The program is in the scope of 14 million NIS Funded by VT and a number of philanthropic foundations: the Yad Hanadiv Foundation, the Kellerman Family Foundation, the Russell Berry Foundation and the Wolfson Foundation. The program will be operated by the National Science Foundation. In the framework of this dedicated budgeting, the intention is to finance approximately 30 Projects in the scope of 180,000-720,000 NIS for research that will last between six months and two years.

The new projects that won funding

Below is the list of the 16 selected research proposals, which includes the names of the researchers and their specialization, the research topic and the total amount of the grant:

1. Prof. Eli Pikarski, School of Medicine, Hebrew University (Immunology and Cancer Research and Department of Pathology), Prof. Itamar Wilner, the Hebrew University (Institute of Chemistry), Dr Oren Ferns, The Hebrew University, (Immunology and Cancer Research), Prof. Rachel Nehushtai, The Hebrew University, (Plant and Environmental Sciences). Total grant: 2 million NIS.

Nano code - finding the right drug for cancer treatment using nanoparticles in a patient: Determining the sensitivity spectrum of an individual cancer to a broad spectrum of different drugs is a central goal of personalized oncology. A new method will be developed for the rapid detection with improved utility of the sensitivity of specific ovarian cancer to many drugs. The research connects scientists with multidisciplinary expertise including nanoparticles, nanochemistry, cancer biology, pathology and systems biology and will use smart nanoparticles, which respond to specific signals in cancer cells and make it possible to determine at once the activity of many anti-cancer drugs.

2. Prof. Eyal Gottlieb, the Technion (Faculty of Medicine named after Ruth and Baruch Rappaport), Dr Jacob Richard Lawrence, Sheba - Academic Medical Center (Institute for Oncological Radiotherapy), Dr Yitzhak Foundation, the Technion (Faculty of Medicine), Dr Talia Golan, Sheba - Academic Medical Center (Oncology Institute). Total grant: 9 million NIS.

Using genomics and metabolomics to identify susceptibility to inhibitors PARP and overcoming resistance to treatment of pancreatic cancer tumors: Pancreatic cancer is a malignant disease that usually does not respond well to conventional treatments. Recently, a subgroup of pancreatic cancer patients was discovered in which the cancerous tumor was formed due to damage to the genetic repair mechanism. Therefore, these tumors respond better to drugs that cause DNA damage. However, even these tumors develop resistance to treatment relatively quickly. Combining genetics and biochemistry, the research will map the metabolic profile of these tumors in order to understand the resistance mechanisms and find ways to overcome them.

3. Prof. Dror Sharon, Hadassah Ein Kerem University Hospital (ophthalmology department), Prof. construction magnate, Hadassah Ein Kerem University Hospital (ophthalmology department), Prof. Shay Ben-Aroya, Bar-Ilan University (Faculty of Life Sciences), Dr Shai Carmi, The Hebrew University, (Faculty of Medicine, School of Public Health). Total grant:2 million NIS.

Hereditary retinal diseases - identifying genes and risk factors for the development of a new method for personalized medicine: Hereditary diseases of the retina are a major cause of vision impairment, sometimes to the point of blindness, and are accompanied by a severe impairment of the quality of life of the sufferer as well as a considerable socio-economic burden at the level of society. Most of these diseases still do not have an effective cure, but in recent years, breakthrough therapies have begun to develop that take their first steps in this field, including gene and cell healing. In the proposed study, we will use national epidemiological resources and innovative developments in the field of personalized medicine to characterize, diagnose and improve the treatment of patients with hereditary degenerative retinal diseases. The hope and expectation is that the results of the research will enable a better understanding of the biology and epidemiology of these diseases, while paving new ways to improve their detection, diagnosis, genetic counseling, prevention and treatment. The research was done in collaboration The health funds are unified and general.

4. Dr Michael Berger, The Hebrew University, (Immunology and Cancer Research, School of Medicine), Dr Dinora Friedman - Morbinski, Tel Aviv University (biochemistry and molecular biology), total grant:75 million NIS.

Cellular immunotherapy of glioblastoma CAR T With double specificity and improved metabolism: The use of T cells with a chimeric receptor (CAR-T) to treat glioblastoma (GBM) has had limited success due to two issues, tumor evasion by molecular change, and metabolic exhaustion of the CAR-T cells due to a lack of nutrients in the tumor environment. To overcome these obstacles, CAR T cells with dual specificity and improved metabolism will be developed, which will attack the GBM tumors through two different molecules and which will be genetically programmed to overcome a lack of glucose and oxygen. The study is expected to provide a new approach and practical tools for personalized treatment in GBM, and is therefore essential to advance the CAR-T from a promising treatment to an effective treatment. The research was done in collaboration Sheba Tel Hashomer Medical Center.

5. Prof. Thelma Handler, Tel Aviv University (School of Psychological Sciences and Sagol School of Neuroscience, Faculty of Medicine), and the Tel Aviv Sourasky Medical Center; Prof. Noam Shomron, Tel Aviv University (Edmund Safra Center for Bioinformatics and Segol School of Neuroscience, Faculty of Medicine) Prof. Malka Gurfein, Tel Aviv University (Department of Statistics and Performance Research, School of Mathematics); Prof. Lior Wolff, Tel Aviv University (Computer Science); Facebook Israel AI Research Group. Total grant:5 million NIS.

A dynamic risk assessment model for post-traumatic psychopathology based on multi-layered personal characterization in different time scales of the stress response: Stress is common in our lives and affects the health of the body and mind. The stress response is multi-layered; biological and psychological and changes over time. People differ from each other in response to stress and it was impossible to predict who would develop a pathological reaction over time. By combining knowledge from neuroscience, psychiatry, genetics, statistics and computer science (AI), the researchers plan to build a computational model that will predict the risk near a traumatic event, the development of mental problems over time, and aim for personalized treatment. The model will be a basis for similar developments in other mental disorders where development over time is critical in characterizing the psychopathology and improving treatment.

6. Prof. Gil Ast, Tel Aviv University (Department of Human Molecular Genetics and Biochemistry); Prof. Rodad Sharan, Tel Aviv University (School of Computer Science). Total grant: 9 million NIS.

Deciphering the involvement of epigenetic mechanisms in autism and tailoring personalized treatment: Autism spectrum disorders have a clear genetic component, but genetic changes that are common in patients are also found in healthy people. We found two genes with high expression in autism, which may be involved in the penetrance of the disorder, because their overexpression in a cellular system causes epigenetic changes in the whole genome, and specifically in genes linked to autism. In the study we will examine cells from sick and healthy subjects who have the same genetic change that characterizes autism and compare them according to epigenetic parameters, splicing patterns and gene expression patterns. Also, a machine learning-based tool for diagnosing autism was developed and a system was developed for changing methylation patterns for personalized treatment. The research was done in collaboration Center for Autism Research at Ben Gurion University).

7. Prof. Benjamin Dekal, Sheba - Academic Medical Center (Director of the Institute for Pediatric Stem Cell Research and the Pediatric Nephrology Unit); Dr Tomer Kalisky, Bar-Ilan University (Department of Biomedical Engineering); Prof. Yair Anixter, Sheba - Academic Medical Center (Director of the Metabolic Unit). Total grant: 75 million NIS.

Creating a model for tubulopathy using patient-matched kidney organs for the purpose of personalized renal treatment - Mitochondrial Panconi syndrome as a proof of feasibility: The research proposal revolves around taking urine from patients, isolating stem cells from the urine and building kidney tissue outside the body that simulates the activity of the kidney (organoids). Specifically, urine will be taken from children with mitochondrial diseases that have kidney damage. From these variables we will build each patient's own tissue in culture, and we will learn about pathways that are affected by the disease, then we will incubate the organoids with different drugs to find which one will improve the function of the mitochondria and may cure the patients.

8. Prof. Ido colleague, Weizmann Institute of Science (Department of Immunology); Dr Moshe Gat, Hadassah Ein Kerem University Hospital (Hematology); Dr Hamotel Gur, Hadassah Ein Kerem University Hospital (internal wing); Dr Yael Cohen, the Sourasky Tel Aviv Medical Center (the hematological unit) and Tel Aviv University (the Faculty of Medicine). Total grant: 2 million NIS.

Sequencing of individual cells from the bone marrow and blood of multiple myeloma patients - for the development of diagnostic markers and personalized immunotherapy: Multiple myeloma is the second most common blood cancer in the world. Despite significant advances in treatment methods, multiple myeloma is still incurable. The research will create breakthroughs in the understanding of multiple myeloma, and will provide doctors with powerful molecular tools for early detection of the disease, predicting the effect of different treatment plans, and discovering new drugs for multiple myeloma.

9. Prof. Yoram Reiter, Biology, Technion - Israel Institute of Technology, Prof. Miriam Ben-Harosh, Rambam - the medical college for human health (hematology-oncology children). Total grant: 925 million NIS.

A novel approach to overcoming resistance to cell therapy T  Engineered by antibodies targeting the intracellular proteome: In recent years, there has been tremendous progress in cancer immunotherapy, especially in hematological malignancies, using engineered cells of the immune system in an approach called CAR-T cell therapy. However, about 60% of patients develop resistance at some stage of the treatment resulting from modulation of the antigen that is expressed on the surface of the cell and against which the engineered cells are directed. In the study, the researchers intend to develop an innovative approach that will overcome this resistance. The approach is based on novel antibodies that target parts of that surface protein that has been modulated but they now recognize small parts of it that are of intracellular origin. These parts of the protein (peptides) are presented on the surface of the cell by a tissue compatible complex (MHC, a natural mechanism of the immune system that enables the recognition of processes occurring inside the cell. Now the antibodies will be directed against the same MHC complex that presents the peptide originating from the diseased cell and thus A new family of engineered cells will be built to attack the diseased cells that have developed resistance.The research could lead to a new family of therapeutic measures for cancer and other diseases.

10. Dr Uri Avinoam, Weizmann Institute of Science (Department of Biomolecular Sciences); Dr Nte Regev-Rotsky, Weizmann Institute of Science (Department of Biomolecular Sciences); Prof. Ziv Gil, the Rappaport Center, the Technion, and Rambam - the Medical College for Human Health; Dr Amnon Bar-Shir, Weizmann Institute of Science (Department of Organic Chemistry). Total grant: 75 million NIS.

The release mechanism of extracellular vesicles from cancer cells: The research will focus on understanding the mechanism that allows "extracellular lobules", biological carriers secreted from cancer cells when they are wrapped in a membrane similar in composition to the cell membrane itself, to mediate various activities that contribute to cancer transformation. This information will be used by researchers to develop methods for the early detection of cancerous transformation, and to produce artificial carriers that will allow drugs to be injected into target cells in a targeted and specific manner.

11. Dr Shai Shen-Or, Technion - Israel Institute of Technology (Faculty of Medicine, Department of Immunology); Prof. Valery Kryzhnovsky, Weizmann Institute of Science (Department of Molecular Cell Biology); Prof. Michal Powell, Rambam - the Medical College for Human Health (Institute of Infectious Diseases). Total grant: NIS 2 million.

Understanding the relationship between immunological age and senescence and their effect on the dynamics of the immune and clinical response to serious infections: Infections are a cause of morbidity that can be fully prevented and treated. The rabbi of the hidden over the visible who will suffer from infection and who will develop a serious infection or a deadly infection. In the study, the researchers will examine how the differences between people in two basic processes of aging: that of the cells in the body, and that of the immune system, affect the ability to deal with infections. The results of the study are expected to yield the patient's ability to predict the severity of the infection and its results in the clinic. The research was done in collaboration Maccabi Health Fund Research Institute.

12. Prof. Rotem Karni, the Hebrew University (School of Medicine); Prof. Cedar of Lebanon, Bar-Ilan University (Faculty of Life Sciences); Prof. Bat Sheva Kerem, the Hebrew University (Department of Genetics, Institute of Life Sciences); Prof. Eitan Kerem, Hadassah University Hospital (Department of Pediatrics). Total grant: 9 million NIS.

A computational and experimental approach to personalized medicine for the diagnosis and treatment of rare genetic diseases: Thousands of rare genetic diseases are known that affect the lives of about one hundred million people, but the vast majority of them have no treatment. This interdisciplinary project includes a new approach to the development of a platform that will enable the application of the information and understanding based on the patient's personal genome towards the design of specific drugs for the specific mutation. The research was done in collaboration Midgem Administration - the Israeli repository for biological samples for research.

13. Prof. Birch deer, Weizmann Institute of Science (Department of Biomolecular Sciences); Prof. Moshe Oren, Weizmann Institute of Science (Department of Molecular Cell Biology); Prof. Baruch Brenner, Rabin Medical Center - Billinson (Davidoff Cancer Center); Dr Tamar Paz-Elitzur, Weizmann Institute of Science (Department of Biomolecular Sciences). Total grant: 9 million NIS.

Individual risk assessment for colon cancer based on natural anti-cancer defense mechanisms: a potential tool for prevention and early detection: The aim of the research is to develop markers for personal risk assessment of colon cancer, one of the most common and deadly cancers. The markers will be based on our body's natural anti-cancer defenses, and will include repair of DNA damage, suicide of pre-cancerous cells, and our immune system. These markers and the risk assessment will be used to prevent bowel cancer, in an effort to reduce the incidence of the disease and mortality from it.

14. Dr Ronan Hazan, the Hebrew University (Institute of Dental Sciences, Faculty of Dentistry); Dr Daniel Barkan, the Hebrew University (Veterinary School, Robert H. Smith Faculty of Food Agriculture and Environment); Prof. Ran Nir-Paz, Hadassah University Hospital (Clinical Microbiology and Infectious Diseases); Prof. Michal Beniasch, the Hebrew University (Lautenberg Center for Immunology, School of Medicine). Total grant: NIS 4.2 million.

Towards personalized medicine of infectious diseases - adjusting optimal personal care using bacteriophages and antibiotics: The current corona crisis has somewhat made the fact that there are other threats, for example the alarming increase in bacteria resistant to antibiotics that lead to the death of about 20 people a day in Israel. The solution that the team of researchers focuses on is the use of viruses called "bacteriophages" that effectively and precisely kill the bacteria. Their great advantage is the researchers' ability to change and adapt them if a resistant bacterium develops. In addition, by virtue of being precise, they, unlike antibiotics, do not cause damage to the "good" microbiome bacteria. Moreover, their accuracy ensures that their treatment will be done in a personalized way for each patient.

15. Prof. Eli Sprecher, Tel-Aviv Sourasky Medical Center (Skin Department); Dr Robbie Shalom-Feuerstein, the Technion - Israel Institute of Technology (Department of Developmental Biology and Genetics); Dr cliff light, The Hebrew University (Department of Statistics). Total grant: 5 million NIS.

Genetic and epigenetic changes that affect disease phenotypes - skin diseases as a paradigm: Much has been written about personalized medicine. The need to adapt treatment to the individual person stems from the fact that the course of diseases, their severity and their response to treatment vary from person to person. These differences are largely dictated by genetic and epigenetic factors. The purpose of the research is to characterize these factors while studying hereditary skin diseases. The researchers hope that the results of this study will lead to the identification of new medicinal targets and the development of innovative therapeutic approaches both for hereditary skin diseases and for more complex and common conditions.

16. Prof. Aharon Blank, Technion - Israel Institute of Technology (Chemistry); Prof. Murir Khamaisy, Rambam - the Medical School for Human Health (Internal Medicine and Endocrinology) and the Faculty of Medicine at the Technion, Prof. Marcel is changing, Technion - Israel Institute of Technology (Biotechnology and Food Engineering), Dr Yaron Fox, the Technion - Israel Institute of Technology (biology). Total grant: 2 million NIS.

A personalized approach to the diagnosis and treatment of chronic wounds in diabetic patients: The aim of the research is the development of new approaches to the diagnosis and personalized treatments of chronic diabetic wounds. More specifically, we plan to offer an innovative way to treat wounds using a specific customized artificial skin graft, which will be combined with customized oxygen therapy. The oxygen treatment will be based on a new magnetic resonance methodology for specific non-invasive monitoring of oxygen levels in wounds.