Project description
Molecular insight into endocytosis
Cells receive substances from their environment through a process known as endocytosis, which transports the desired cargo to vesicles within cells. Endocytosis is also responsible for the recycling of cell surface receptors and adhesion molecules. Funded by the Marie Skłodowska-Curie Actions programme, the ModulEndoA3 project focuses on endophilin-A3 and the mechanism by which it is implicated in the process of endocytosis. The objective is to identify cellular regulators and small molecule inhibitors of endophilin A3-mediated endocytosis. By studying the effects of these modulators on cancer cell properties and viral entry, this research could advance fundamental knowledge and lead to innovative antiviral and anti-cancer therapeutics.
Objective
In addition to classical clathrin-mediated endocytosis, mammalian cells have clathrin-independent endocytic (CIE) mechanisms. Among others, the BAR domain proteins, that sense and induce membrane curvature, are key players in CIE. In particular, the BAR domain protein endophilin-A3 (endoA3) drives CIE of the cell adhesion molecules CD166, L1CAM, and DICAM, with implications in tumour progression and viral infection. The regulation, mechanism, and functional implications of this recently-identified endoA3-mediated CIE route remain poorly characterized. In this context, I propose an interdisciplinary project combining cell biology, chemical biology, and virology approaches to substantially advance our understanding of endoA3-mediated CIE. The first research goal is to identify cellular regulators (kinases, phosphoinositides) that modulate endoA3-mediated endocytosis. In parallel, this project aims at identifying small molecule inhibitors that selectively inhibit the endocytic functions of endoA3. Subsequently, the cellular regulators and pharmacological inhibitors identified in this project will be used in cells, to modulate endoA3-mediated endocytosis and study the impact on cellular functions. Emphasis will be put on cancer cell properties and endocytic viral particle entry. Together, this project will generate high-quality fundamental knowledge on the mechanism and function of endoA3-mediated CIE. Moreover, the identification of modulators of endoA3 endocytic functions will provide valuable biological tools for the study of this recently-identified CIE route in physiology and pathology. Lastly, the identification of selective pharmacological inhibitors may pave the way towards the development of innovative antiviral and anti-cancer therapeutics targeted at unconventional endocytosis. This fellowship will be conducted in the laboratory of Prof. Henri-Francois Renard (UNamur, Belgium), who has been a pioneer in the identification of BAR-mediated endocytic routes.
Fields of science (EuroSciVoc)
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.
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- medical and health sciencesclinical medicineoncology
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiology
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Keywords
Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
5000 Namur
Belgium