Description du projet
Révéler l’interaction des condensats biomoléculaires avec les organites
Les cellules contiennent des structures dynamiques connues sous le nom de condensats biomoléculaires qui se forment par la séparation de phase liquide-liquide des molécules. Ces condensats résultent de l’assemblage de diverses biomolécules, notamment des protéines, des acides nucléiques et parfois des lipides, et contrairement aux organites membranaires traditionnels, ils ne sont pas entourés d’une membrane. Financé par le Conseil européen de la recherche, le projet MEMLESSINTERFACE vise à étudier l’interaction entre les condensats biomoléculaires et les organites membranaires dans les neurones. Les travaux se concentreront sur les condensats biomoléculaires formés au niveau des synapses, leur régulation et leur interaction avec les mitochondries et le réticulum endoplasmique pour assurer la médiation de la fonction neuronale.
Objectif
Liquid-liquid phase separation is a major mechanism for organizing macromolecules, particularly proteins with intrinsically disordered regions, in compartments not limited by a membrane. Many such compartments (also known as biomolecular condensates) have been described, and it is currently agreed that they take over several cellular functions. To do so, they need to interact with other compartments, just as the membrane-bound organelles interact with each other through well-defined contact sites. However, at present no concept exists explaining how membrane-less and membrane-bound organelles interact.
I propose here to address this question by determining the molecular mechanisms and functional impact of the interactions between liquid phases and membranes. I hypothesize that a novel type of contact sites between membrane-less organelles and membranes, which I termed dipping contacts, is critical for coupling of diffusion and material properties of condensates to biochemical processes occurring in the membrane-bound compartments.
To test this, I will capitalize on a prominent biomolecular condensate that I characterized a few years ago, and which has already been used widely in the literature: the synaptic vesicle (SV) condensate, which clusters SVs together with proteins such as synapsins and synucleins. For this, I have already developed advanced reconstitution tools, single-molecule tracking and genetic code expansion in living neurons, which will enable me to determine: i) how the material properties of SV condensates are regulated, ii) how they recruit specific organelles, while rejecting others, iii) the proteins that mediate signaling and interactions of SV condensates with mitochondria and the ER.
Overall, this project will lead to an understanding of the interface between condensates and classical organelles, which is extremely relevant in the context of aggregation-related diseases where faulty inclusions of membranes and proteins play a leading role.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
53127 Bonn
Allemagne