Description du projet
Une nouvelle compréhension des mécanismes cellulaires et de leur rôle dans la santé humaine
Les membranes cellulaires jouent un rôle essentiel dans divers processus biologiques, notamment la fécondation, la division cellulaire et la signalisation cellulaire. Il est essentiel de comprendre les mécanismes qui sous-tendent ces processus afin de concevoir des interventions ciblées susceptibles de les moduler. Dans ce contexte, le projet ReMembrane, financé par l’UE, entend découvrir les mécanismes à l’origine du remodelage des membranes cellulaires, qui sont essentiels à la compréhension de processus biologiques tels que la fécondation et l’infection virale. Le projet se concentrera sur la famille des protéines tétraspanines. Elles jouent un rôle crucial dans la formation des migrasomes, qui assurent la communication entre les cellules. L’approche unique du projet permettra aux chercheurs de caractériser les rôles de la tension et de la courbure des membranes dans les processus biologiques et de fournir des indications sur des traitements potentiels de l’infertilité, des contraceptifs non hormonaux et des médicaments antiviraux.
Objectif
Our bodies rely on protein driven shaping and remodelling of our cells’ membranes to function. Uncovering the mechanisms of remodelling of the cell membrane is, therefore, essential for understanding biological processes such as fertilization, but also to allow for precise intervention in them when needed. The interplay between protein position, membrane tension, and local curvature is believed to dictate these processes. However, experimental verifications of this hypothesis in specific biological systems are scarce. Here, I propose to apply my expertise in the characterization of mechanical properties and remodelling of membranes to obtain ground-breaking quantitative details of the shaping and remodelling mechanisms in which the Tetraspanin (TSPN) family of proteins are involved. TSPNs provide an ideal case study for several reasons, they are of extreme importance to biological processes such as viral infection, they are well characterized by biochemical, genetic and proteomics approaches, and their mode of action is suspected to depend on membrane tension and curvature. Of specific interest is the role of TSPN in the formation of the newly discovered cellular organelles, called migrasomes, which are a new cell-cell communication paradigm. This proposed project addresses TSPN functions by a bottom-up approach, reconstituting the processes of interest from simple building blocks and characterizing the distinguished roles of membrane tension and curvature. To this end we will use several new assays based on combined optical tweezers, micropipette aspiration and confocal microscopy as well as AFM that will operate on crafted membrane model systems. Our unique experimental approach will allow us to recreate the conditions leading to migrasome formation, egg-sperm, and viral membrane fusion. Revealing the mechanisms underlying these processes will have direct impact on the development of infertility treatments, non-hormonal contraceptives, and novel anti-viral drugs.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
ERC - Support for frontier research (ERC)Institution d’accueil
69978 Tel Aviv
Israël