Periodic Reporting for period 1 - GENESIS (unveilinG cEll-cell fusioN mEdiated by fuSexins In chordateS)
Période du rapport: 2020-04-01 au 2022-03-31
Membrane fusion is essential for many physiological and pathological processes: infection of enveloped viruses, fertilization, intracellular trafficking of vesicles and in some cases of organogenesis. These processes are mediated by specific proteins called fusogens. Fusexins are fusogens that are essential for sexual reproduction and exoplasmic merger of plasma membranes in protists, plants, invertebrates and class II enveloped viruses. The main goal of my project is to characterize the least understood class of membrane fusion: sperm-egg fusion process within the phylum Chordata. We evaluated whether proteins from mouse gametes with predicted structural similarities to Fusexins fulfill the two criteria to be considered fusogens (i.e. necessity and sufficiency for membrane fusion). We found that proteins found in the oocyte membrane can mediate fusion of somatic cells in culture indicating a role for these proteins during gamete fusion. Furthermore, during this project we discovered that the sperm adhesion molecule IZUMO1 showed the ability of inducing fusion of cells. This unexpected result suggests a new activity for this protein during fertilization of mammals independent of its well-characterized role as an adhesion protein. I expect that our findings will shed light on the evolution of gamete fusion and on the mechanisms of action of new cell-cell fusogens. This project has the potential to lead to breakthroughs in understanding and manipulating membrane fusion in sexual reproduction, organ development, diseases, and tissue repair.
The different candidate proteins from mammalian gamete were evaluated with a set of experimental approaches to determine whether they are sufficient to mediate the fusion of cells in tissue culture conditions. In addition, we used virus systems to determine whether the candidates can substitute the viral fusogens during the infection of cells. During this work, optimization of the existing protocols for evaluation of the fusogenic activity of the proteins was performed and registered. During the reported period three articles were published: one peer-reviewed review article, one peer-reviewed research article and one pre-print research article. Furthermore, the results were presented in national and international scientific, like the Gordon Research Conference in Cell-Cell fusion 2022. In addition, different aspect of this project were presented in different activities to general audience as well as in social media.
During the development of the research and training project GENESIS, my skills and capabilities as researcher were significantly enhance. I had the opportunity to learn and improve state-of-the-art techniques to evaluate the ability of proteins to induce membrane fusion used commonly in Podbilewicz lab. In addition to the new experimental techniques that I have acquired, working in this project allowed me to improve my scientific management skills, mentoring experience and networking opportunities. I was actively involved not only in writing of reports and scientific papers, but also the submission of grants and reviewing of papers.
I was involved in the mentoring and training of undergraduate students and participated as a lecturer in different courses related to Developmental biology and reproduction. Finally, throughout the reported period I had the chance to interact and collaborate with researchers from the Technion, other prestigious research centers in Israel, and collaborators in Europe, North and South America and Asia. Altogether, the activities performed during GENESIS significantly impulse my personal growth towards scientific independence.
During the development of the research and training project GENESIS, my skills and capabilities as researcher were significantly enhance. I had the opportunity to learn and improve state-of-the-art techniques to evaluate the ability of proteins to induce membrane fusion used commonly in Podbilewicz lab. In addition to the new experimental techniques that I have acquired, working in this project allowed me to improve my scientific management skills, mentoring experience and networking opportunities. I was actively involved not only in writing of reports and scientific papers, but also the submission of grants and reviewing of papers.
I was involved in the mentoring and training of undergraduate students and participated as a lecturer in different courses related to Developmental biology and reproduction. Finally, throughout the reported period I had the chance to interact and collaborate with researchers from the Technion, other prestigious research centers in Israel, and collaborators in Europe, North and South America and Asia. Altogether, the activities performed during GENESIS significantly impulse my personal growth towards scientific independence.
Human fertility disorders affect around 10% of couples worldwide. Despite of the relevance of the fertilization process and the multiple infertility conditions in humans, the molecular mechanisms underlying gamete interactions are poorly understood. The information obtained by GENESIS have many potential applications in reproductive: it may lead to the development of new infertility treatments and contraceptives methods, as well as vaccines to block parasites’ fertilization. In a wider sense, understanding the molecular basis of membrane fusion may also have a positive impact on other research areas, such us the study of regenerative medicine and infectious diseases.