Project description DEENESFRITPL Common cellular mechanisms can lead to creation or destruction depending on the cell type Cells are surrounded by membranes that separate internal and external environments. In addition, cells are loaded with membrane-bound organelles and membrane-bound trafficking vesicles. This compartmentalisation is critical to cell and system function but so is moving things around among compartments. Nature has a solution with organised and controlled fusion of membranes for intermingling mediated by specialised proteins called fusogens. Among these is the newly identified Hapless2 Male Gamete Fusion Factor (Fusexin) superfamily. GENESIS is hoping to isolate one of the first-reported Fusexins from mouse gametes to study fusion mechanisms in processes including sexual reproduction and viral infection. Enhanced understanding could impact in vitro fertilisation, vaccine development and numerous other applications of tremendous medical import. Show the project objective Hide the project objective Objective 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: cell-cell fusion processes within the phylum Chordata mediated by proteins from the Fusexin superfamily. I will evaluate 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). In parallel, I will elucidate the mechanisms of action of the amphioxus Br-FF-1 proteins, the first Fusexins described in Chordata. The project involves both high risk and feasible objectives, employing assays that are well established in the Podbilewicz lab as well as the development of new techniques (including in vitro fertilization assays, fusion in heterologous cells, pseudotyping of viruses and virus-cell infection). I expect that results obtained will shed light on the evolution of the Fusexin superfamily that maps to the beginning of the eukaryotic cells and enveloped viruses, and thoroughly characterize the mechanisms of action of cell-cell fusogens. My proposal has the potential to lead to breakthroughs in understanding and manipulating membrane fusion in sexual reproduction, organ development, diseases and tissue repair. Fields of science medical and health scienceshealth sciencesinfectious diseasesRNA virusesnatural sciencesbiological sciencesmicrobiologyvirologynatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological scienceszoologyinvertebrate zoology Keywords Fusion Fertilization Sperm Egg Membranes Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2018 - Individual Fellowships Call for proposal H2020-MSCA-IF-2018 See other projects for this call Funding Scheme MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Coordinator TECHNION RESEARCH AND DEVELOPMENT FOUNDATION LTD Net EU contribution € 173 464,32 Address THE SENATE BUILDING TECHNION CITY 1 32000 Haifa Israel See on map Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 173 464,32
