Objective
Reversible protein modifications act as key switches regulating numerous cellular processes. In contrast, our most abundant protein modification, N-terminal (Nt) acetylation, has for decades been considered static and irreversible. This project aims to identify regulatory Nt-acetylation events (Nt-switches) and establish their crucial role in human biology.
A relevant place to look for Nt-switches is at neo-N-termini. These are generated by proteases, for example the signal peptide cleavage of proteins entering the endoplasmic reticulum (ER), or the maturation of bioactive peptides in the secretory pathway. The bioactive peptides that regulate appetite and pain are particularly interesting since it is known that their neo-N-termini are Nt-acetylated, which has critical effects for their biological activity. ER chaperones are also Nt-acetylated, as our unpublished data has uncovered. This occurs in response to cellular stress when ER chaperones move to the cytosol. Here, Nt-acetylation competes with another Nt-modification to potentially control protein degradation, autophagy, cell migration and other stress responses. Our data also suggest that Nt-acetylation is dynamic and reversible, but the enzymes responsible for post-translational Nt-acetylation of bioactive peptides and ER-chaperones and protein Nt-deacetylation have not yet been identified. The biological regulation mediated by Nt-switches is therefore not yet mechanistically understood.
The objective of this project is to uncover how Nt-acetylation steers protein fate and how Nt-switches are involved in biological regulation. Our recently developed cell models, enzyme assays, modification-specific antibodies and biochemical, chemical biology and proteomics approaches will identify and define the human enzymes adding, removing or competing with Nt-acetylation. This project will establish the Nt-switch concept and unravel its impact on the processes of autophagy, cell migration and metabolism.
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.
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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-2025-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.
5020 Bergen
Norway
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.