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unveilinG cEll-cell fusioN mEdiated by fuSexins In chordateS

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.

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Programme(s)

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Topic(s)

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Funding Scheme

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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)

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Call for proposal

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(opens in new window) H2020-MSCA-IF-2018

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Coordinator

TECHNION RESEARCH AND DEVELOPMENT FOUNDATION LTD
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 173 464,32
Address
THE SENATE BUILDING TECHNION CITY 1
32000 Haifa
Israel

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Activity type
Private for-profit entities (excluding Higher or Secondary Education Establishments)
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 173 464,32
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