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Financement de l’UE (11,2 M €) : Les phases de protéines ressemblant à des cristaux liquides organisent-elles les compartiments membranaires ? Hor22/01/2021 Programme de recherche et d'innovation de l'UE « Horizon »
Texte
Les phases de protéines ressemblant à des cristaux liquides organisent-elles les compartiments membranaires ?
We are in the midst of a revolution in our understanding of the internal organization of cells. In the 1950s we learned that lipid bilayer-based membranes serve as containers (organelles) within the cytoplasm. Now we are learning that liquid-like membrane-less organelles i.e. without any container, self-assemble based on liquid-liquid phase separations. We propose the seemingly radical idea that membrane-bounded organelles like their membrane-less counterparts- are stabilized or even templated by analogous phase separations of their surface proteins into largely planar liquids akin to liquid crystals. Our unique Synergy team is organized specifically to test this liquid crystal hypothesis on the cells secretory compartments - ER exit sites (ERES) and the Golgi stack - by employing our complementary skills in physics, physical chemistry, biochemistry and cell biology. We hypothesize based on pilot experiments evidence that the ERES and Golgi self-organize as a multi-layered series of adherent liquid crystal-like phases of golgin and similar proteins which surround and enclose their membranes. Their differential adhesion and repulsion would specify the topology and dynamics of the membrane compartments. If this is true, it will literally rewrite the history of cell biology. We will test the liquid crystal hypothesis directly, systematically, and quantitatively on an unprecedented scale to either modify/disprove it or place it on a firm rigorous footing. Experiments (Aim 1) with 13 pure golgins in cis and trans pairwise combinations will establish their foundational physical chemistry. Surgically engineered changes in golgins/ERES proteins will alter the rank order (hierarchy) of their affinities for each other and link phase separation physics to cell biology (Aim 2) and be used to establish the structural basis of phase separations and their specificity, and the potential for self-assembly of wholly synthetic biological organelles (Aim 3).
| Centre National de la Recherche Scientifique CNRS | 2 922 775 € |
| Fundacio Centre de Regulacio Genomica | 2 421 410 € |
| Sorbonne Universite | 0,00 € |
| Universidad Complutense de Madrid | 2 553 940 € |
| University College London | 3 339 375 € |
https://cordis.europa.eu/project/id/951146
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel.
