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Deciphering Cellular Networks for Membrane Protein Quality Control Decisions

Objective

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.

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 for secreted proteins, our understanding 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?

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

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Call for proposal

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(opens in new window) ERC-2022-COG

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Host institution

TECHNISCHE UNIVERSITAET MUENCHEN
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 1 975 000,00
Address
Arcisstrasse 21
80333 Muenchen
Germany

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Region
Bayern Oberbayern München, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 975 000,00

Beneficiaries (1)

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