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 of 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 |
|---|---|---|---|---|
MANUNKIND: Determinants and Dynamics of Collaborative ExploitationThis project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery. | ERC STG | € 1.497.749 | 2022 | Details |
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressureThe UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance. | ERC STG | € 1.498.280 | 2022 | Details |
Uncovering the mechanisms of action of an antiviral bacteriumThis project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function. | ERC STG | € 1.500.000 | 2023 | Details |
The Ethics of Loneliness and SociabilityThis project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field. | ERC STG | € 1.025.860 | 2023 | Details |
MANUNKIND: Determinants and Dynamics of Collaborative Exploitation
This project aims to develop a game theoretic framework to analyze the psychological and strategic dynamics of collaborative exploitation, informing policies to combat modern slavery.
Elucidating the phenotypic convergence of proliferation reduction under growth-induced pressure
The UnderPressure project aims to investigate how mechanical constraints from 3D crowding affect cell proliferation and signaling in various organisms, with potential applications in reducing cancer chemoresistance.
Uncovering the mechanisms of action of an antiviral bacterium
This project aims to uncover the mechanisms behind Wolbachia's antiviral protection in insects and develop tools for studying symbiont gene function.
The Ethics of Loneliness and Sociability
This project aims to develop a normative theory of loneliness by analyzing ethical responsibilities of individuals and societies to prevent and alleviate loneliness, establishing a new philosophical sub-field.
Vergelijkbare projecten uit andere regelingen
| 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 STG | € 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 ADG | € 2.136.875 | 2022 | Details |
Mechanisms of co-translational assembly of multi-protein complexesThis project aims to uncover the mechanisms of co-translational protein complex assembly using advanced techniques to enhance understanding of protein biogenesis and its implications for health and disease. | ERC SyG | € 9.458.525 | 2023 | 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 STG | € 1.498.832 | 2023 | 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 co-translational assembly of multi-protein complexes
This project aims to uncover the mechanisms of co-translational protein complex assembly using advanced techniques to enhance understanding of protein biogenesis and its implications for health and disease.
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.