Project description
Uncovering the impact of nePTMs on protein turnover
Inside living cells, proteins are continuously exposed to reactive metabolites that introduce non-enzymatic post-translational modifications (nePTMs), such as oxidation, carbonylation, glycation, or carbamylation. nePTMs can irreversibly block critical interaction sites and pose a threat to proteome integrity. nePTM-bearing proteins are selectively degraded in healthy cells by an unknown mechanism that recognises and eliminates them. The EU-funded PRO-CLEAR project will study the impact of nePTMs on protein turnover and explore the underlying molecular mechanisms. It will test the effects of nePTMs and identify the adducts that induce protein clearance. PRO-CLEAR project aims to uncover a novel pathway for the quality control of chemically damaged proteins that will form the basis for understanding its role in physiology and human diseases.
Objective
Cellular homeostasis and survival critically depend on the ability to remove misfolded and damaged proteins. In cells, proteins are continuously exposed to reactive metabolites which introduce modifications such as oxidation, carbonylation, glycation or carbamylation. Such non-enzymatic post-translational modifications (nePTM) can irreversibly block critical interaction surfaces or reactive sites and thus pose a constant threat to proteome integrity. In line with this view, levels of nePTM are increased in diseased and aged tissues. In contrast, nePTM-bearing proteins are selectively degraded in healthy cells, suggesting the existence of a so far unknown pathway that recognizes and eliminates nePTM-bearing proteins.
In this project, I will study the impact of nePTMs on protein turnover and explore the underlying molecular mechanisms. More specifically, I plan to (I) establish a reporter assay to monitor the degradation of proteins displaying individual amino acid modifications in human cells. This will allow to test effects of common nePTMs and to identify the precise chemical adducts that induce protein clearance. Aim (II) is to uncover the cellular machinery that mediates nePTM-triggered protein degradation. To this end, I will perform a genome-wide CRISPR screen for genes required to eliminate a fluorescent model substrate. Aim (III) of the project is to understand the mechanisms underlying the recognition and clearance of nePTMs. I will therefore characterize one newly identified mediator of nePTM-clearance in detail and test its ability to bind, degrade or modify nePTM-bearing proteins and will study the impact of its knockout on the turnover of endogenous proteins.
Together these experiments promise to uncover a novel pathway for the quality control of chemically damaged proteins which will form the basis for understanding its role in physiology and human disease.
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
- natural sciences chemical sciences electrochemistry electrolysis
- natural sciences biological sciences cell biology
- natural sciences chemical sciences organic chemistry amines
- 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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H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions
MAIN PROGRAMME
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H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility
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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.
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)
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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) H2020-MSCA-IF-2019
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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.
8092 Zuerich
Switzerland
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.