Project description
Key principles of translation regulation and proteostasis
Chaperone proteins play a central role in maintaining proteostasis by assisting the folding of newly synthesised proteins and stabilising components of the protein synthesis machinery. Through these functions, they help coordinate protein production with the cell’s physiological needs. The ERC-funded CHAPEROME project aims to explore how molecular chaperones influence mRNA translation in human cells under normal conditions, during proteotoxic stress and throughout cellular differentiation. It will identify the dependencies of translation factors on chaperones and investigate how these interactions affect translation rates and efficiency. By clarifying the relationship between protein synthesis and protein folding, the project will advance understanding of translational control and help identify potential targets for diseases associated with proteostasis dysregulation.
Objective
CHAPEROME aims to establish a new concept in which molecular chaperones regulate central aspects of mRNA translation in human cells under physiological conditions, in response to proteotoxic stress, and during cellular differentiation. Recent findings indicate that the folding of translation factors relies on specific chaperone proteins to achieve their functional states. We hypothesize that chaperones play a pivotal role in aligning translation rates, efficiency, and mRNA selection with the cell’s proteostasis needs, thus acting as folding sensors that link protein synthesis to cellular demands. Testing this hypothesis requires collaboration among experts in translation, nascent chain folding, and chaperone mechanisms. Establishing this new concept for regulation of translation involves a comprehensive identification of chaperone dependencies of translation factors, which will reveal how chaperone networks control their functionality and impact translation rate and efficiency (Aim 1). We will elucidate the mechanisms by which chaperones and cofactors regulate elongation rates through interactions with nascent protein chains and translation factors, showing new connections between translation and protein folding under physiological conditions. Inducing proteotoxic stress to trigger chaperone overload will reveal the importance of chaperone regulation of translation (Aim 2). Finally, we will examine the new concept in the context of cellular differentiation, to understand how translation and chaperone networks adapt to drastic changes in cell type-specific proteome needs. This will provide novel insight into the plasticity of the translation-chaperone regulatory systems (Aim 3). This interdisciplinary and synergistic effort will reveal new key principles of translation regulation, proteostasis, and cell differentiation, potentially identifying novel targets for diseases associated with translation dysregulation.
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.
- natural sciences biological sciences biochemistry biomolecules proteins proteomics
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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)
MAIN PROGRAMME
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Topic(s)
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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.
Funding Scheme
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.
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.
HORIZON-ERC-SYG - HORIZON ERC Synergy Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-SyG
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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.
80539 MUNCHEN
Germany
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.