Project description
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.
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
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
Keywords
Programme(s)
Funding Scheme
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinator
32000 Haifa
Israel