Description du projet
Assemblage de protéines dans l’organisation des organites: est-il temps de revisiter l’histoire de la biologie?
On sait que l’organisation intracellulaire en organites repose sur la formation de bicouches lipidiques et permet aux cellules de compartimenter différents processus. Cependant, l’existence de compartiments non liés à la membrane, tels que les nucléoles, soulève la question de savoir comment les cellules maintiennent une distinction entre ces régions et empêchent leur contexte de se mélanger avec le milieu environnant. Le projet LiquOrg, financé par l’UE, remettra en question le concept selon lequel les organites sans membrane sont formés par séparation de phase liquide-liquide et proposera une hypothèse faisant intervenir des cristaux liquides, où les protéines de surface s’organisent en plusieurs couches qui entourent et enferment leurs membranes. Les chercheurs se serviront de l’appareil et des protéines de Golgi comme preuve de concept.
Objectif
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 cell’s 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).
Champ scientifique
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ERC-SyG - Synergy grantInstitution d’accueil
75794 Paris
France