Project description
Decoding membrane protein biogenesis and quality control in the endoplasmic reticulum
Membrane proteins are essential for cellular movement and defence, with humans using about one third of their genes to produce them. Problems in their biogenesis can lead to diseases such as cancer. Most membrane proteins are made in the endoplasmic reticulum (ER), but many aspects of this process remain unclear. The ERC-funded DeCoDe project aims to study how quality control factors influence protein folding, determine whether proteins are chaperoned or degraded, and explore the collaboration of chaperones in membrane protein biogenesis. Additionally, it will identify novel chaperones and quality control factors in the mammalian ER.
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
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- agricultural sciences agriculture, forestry, and fisheries agriculture agronomy plant protection
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences clinical medicine oncology
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
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Call for proposal
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(opens in new window) ERC-2022-COG
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80333 Muenchen
Germany
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