Description du projet
Décoder la communication intracellulaire
Les cellules eucaryotes contiennent des organites membranaires qui leur permettent de compartimenter les processus biochimiques et biologiques. Le réticulum endoplasmique (RE) joue un rôle essentiel en facilitant la communication précise entre les organites et en fournissant des protéines et des lipides. Financé par le Conseil européen de la recherche, le projet conNEctoER comble une lacune dans les connaissances scientifiques relatives aux mécanismes régissant les jonctions entre le RE et l’enveloppe nucléaire (EN). Des découvertes récentes suggèrent une ultrastructure dynamique de ces jonctions au cours du cycle cellulaire, ce qui incite à étudier le rôle des protéines membranaires. En combinant la microscopie électronique et l’imagerie en direct, les chercheurs cherchent à élucider la formation et la fonction de la jonction RE-EN, ce qui permet de mieux comprendre l’expression des gènes, l’organisation nucléaire et les mécanismes pathologiques.
Objectif
Compartmentalization into membrane-bound organelles is a key feature of all eukaryotic cells, and communication between organelles needs to be tightly controlled. A key organelle for the inter-organelle communication is the endoplasmic reticulum (ER), which is the major site of lipid and membrane protein synthesis. The ER exchanges molecules by forming stable contact sites with multiple organelles such as mitochondria via specific tethering proteins and transporters. In contrast to these contact sites, the ER is linked to the nucleus via direct fusion to the outer nuclear membrane of the nuclear envelope (NE). These ER-NE junctions are essential for supplying the lipids and proteins that are synthesized in the ER to the NE. Hence, nuclear function and morphology depend on the proper communication via ER-NE junctions. However, the biogenesis, architecture and maintenance of ER-NE junctions have remained elusive.
We have recently found that ER-NE junctions exhibit a narrow and constricted ultrastructure during the cell cycle in mammalian cells. These observations led us to postulate that ER-NE junctions are formed and maintained by specific membrane-shaping proteins that are crucial for nuclear function. Here, we propose to identify the molecular mechanism that governs the structure and function of ER-NE junctions. We will provide a quantitative and dynamic high-resolution view of these enigmatic structures by combining time-resolved electron microscopy and quantitative live imaging with molecular perturbations. Using these datasets, we aim to develop a mechanistic model of how ER-NE junctions form and contribute to nuclear function.
The NE proteins supplied via ER-NE junctions have critical roles in gene expression, nuclear organization, and nuclear pore biogenesis, as well as in differentiation, development, and disease. Therefore, our research will provide a new conceptual framework that will open lines of investigation in many fields beyond ER/NE biology.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
1090 Wien
Autriche