SubsidieMeestersDeciphering Cellular Networks for Membrane Protein Quality Control Decisions
This project aims to enhance understanding of membrane protein biogenesis and quality control in the endoplasmic reticulum, addressing key questions related to folding, chaperones, and disease mechanisms.
Projectdetails
Introduction
Any cell and each of its organelles needs to interact with its environment. Membrane proteins, which span the plasma membrane and the multiple endomembranes of a eukaryotic cell, mediate these interactions. They allow cells to move, thrive, and defend - and multicellular organisms to exist. Humans dedicate almost one third of their genes to membrane proteins. Failures in membrane protein biogenesis or function cause numerous human diseases, from cancer to neurological disorders.
Background
By far, most eukaryotic membrane proteins are produced at one organelle, the endoplasmic reticulum (ER), where a dedicated protein folding and quality control machinery supports and controls protein structure formation. In contrast to our comprehensive understanding of secreted proteins, our understanding of how cells support and control the biogenesis of membrane proteins is still limited.
To further advance our understanding in this key area in molecular cell biology is the major aim of this proposal. Using recent biochemical and cell biological techniques combined with newly developed tools, we will address the following major questions:
- How do cellular quality control factors determine the folding state of a membrane protein?
- Which molecular signatures underlie the decision to chaperone or to degrade a membrane protein?
- How do chaperones collaborate in membrane protein biogenesis?
- Which further membrane protein chaperones and quality control factors exist in the mammalian ER?
Objectives
Answers to these questions will be major steps forward in our understanding of the inner workings of cells but also of the mechanisms underlying membrane protein-associated diseases. Three objectives will serve this goal:
- Objective 1: Define signatures of intramembrane quality control decisions
- Objective 2: Dissect chaperone synergies in membrane protein biogenesis
- Objective 3: Identify novel membrane protein chaperones by functionally validated interactome analyses
Financiële details & Tijdlijn
Financiële details
| Subsidiebedrag | € 1.975.000 |
| Totale projectbegroting | € 1.975.000 |
Tijdlijn
| Startdatum | 1-6-2023 |
| Einddatum | 31-5-2028 |
| Subsidiejaar | 2023 |
Partners & Locaties
Projectpartners
- TECHNISCHE UNIVERSITAET MUENCHENpenvoerder
Land(en)
Vergelijkbare projecten binnen European Research Council
| Project | Regeling | Bedrag | Jaar | Actie |
|---|---|---|---|---|
Deciphering co-translational protein folding, assembly and quality control pathways, in health and diseaseThis project aims to elucidate co-translational protein folding and degradation mechanisms to understand misfolding diseases and improve therapeutic strategies. | ERC Starting... | € 1.412.500 | 2022 | Details |
In situ analysis of chaperone mediated protein folding and stabilityThis project aims to investigate the dynamic role of molecular chaperones in protein folding and maintenance within live cells using advanced imaging and biochemical techniques. | ERC Advanced... | € 2.136.875 | 2022 | Details |
Mechanisms of human co-translational quality control and it’s role in neural tissue.This project aims to elucidate the mechanisms of ribosome-associated quality control in humans and its implications for neurodegeneration and aging, using cryo-EM and C. elegans models. | ERC Starting... | € 1.500.000 | 2024 | Details |
Stress-induced structural and organizational adaptations of the cellular translation machineryThis project aims to investigate how cellular strategies for maintaining protein homeostasis affect ribosome structure and organization under stress, using cryo-electron tomography for detailed insights relevant to neurodegenerative diseases. | ERC Starting... | € 1.498.832 | 2023 | Details |
3-dimensional Organization and Functions of Translation in Organelle ProximityThis project aims to uncover the mechanisms linking translation regulation and organelle biogenesis using functional genomics and cryo-ET to map and understand proximal translation in eukaryotic cells. | ERC Starting... | € 1.999.838 | 2025 | Details |
Deciphering co-translational protein folding, assembly and quality control pathways, in health and disease
This project aims to elucidate co-translational protein folding and degradation mechanisms to understand misfolding diseases and improve therapeutic strategies.
In situ analysis of chaperone mediated protein folding and stability
This project aims to investigate the dynamic role of molecular chaperones in protein folding and maintenance within live cells using advanced imaging and biochemical techniques.
Mechanisms of human co-translational quality control and it’s role in neural tissue.
This project aims to elucidate the mechanisms of ribosome-associated quality control in humans and its implications for neurodegeneration and aging, using cryo-EM and C. elegans models.
Stress-induced structural and organizational adaptations of the cellular translation machinery
This project aims to investigate how cellular strategies for maintaining protein homeostasis affect ribosome structure and organization under stress, using cryo-electron tomography for detailed insights relevant to neurodegenerative diseases.
3-dimensional Organization and Functions of Translation in Organelle Proximity
This project aims to uncover the mechanisms linking translation regulation and organelle biogenesis using functional genomics and cryo-ET to map and understand proximal translation in eukaryotic cells.