Objective
Molecular chaperones mediate protein folding and conformational maintenance. Failure of these fundamental cellular functions results in a breakdown of protein homeostasis (proteostasis) and facilitates the manifestation of diseases associated with protein aggregation. Much progress has been made in understanding the mechanisms of individual chaperone systems, such as the Hsp70s and the chaperonins, based on analyses in vitro. How these machineries function in the intact cell is not well understood, however. The goal of this proposal is to observe and characterize the dynamic action of the major chaperone systems and their interplay in intact cells in real time.Using live cell single molecule imaging combined with biochemical analyses, proteomic profiling, and genetic screening, we will address the following questions:
i) How does the chaperone machinery assist protein chains during and after translation to achieve folding and assembly? We will develop single particle tracking to monitor the chaperone engagement of nascent chains in situ in mammalian cells.
ii) How is the conformational stability of chaperone clients assessed, maintained and triaged in healthy cells and in cells burdened with pathological aggregates? We will track the interactions of metastable proteins with chaperones and proteolytic machinery.
iii) What is the efficiency of protein folding across the proteome under normal conditions and in chaperone-deficient cells? Pulse proteolysis/mass spectrometry will be developed to analyze the folding of nascent polypeptides and will be scaled to analyze the entire proteome of different cell types. By depleting specific proteostasis components we will explore the capacity of the chaperone network for compensatory rewiring and identify vulnerable proteins with an obligate chaperone dependence.
Overall, this work will employ new technology to advance our understanding of the chaperone system in protein folding and proteome maintenance at the cellular level.
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
- medical and health sciences basic medicine physiology homeostasis
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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)
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.
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 - HORIZON ERC 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-2021-ADG
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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.