Objective
My lab studies how cells regulate their growth and metabolism during normal development and in disease. Recent work in my lab, published last year in Nature, identified the metabolite stearic acid (C18:0) as a novel regulator of mitochondrial function. We showed that dietary C18:0 acts via a novel signaling route whereby it covalently modifies the cell-surface Transferrin Receptor (TfR1) to regulate mitochondrial morphology. We found that modification of TfR1 by C18:0 ('stearoylation') is analogous to protein palmitoylation by C16:0 - it is a covalent thio-ester link and requires a transferase enzyme. This work made two conceptual contributions. 1) It uncovered a novel signaling route regulating mitochondrial function. 2) Relevant to this grant application, we found by mass spectrometry multiple other proteins that are stearoylated in mammalian cells. This thereby opens a new avenue of research, suggesting that C18:0 signals via several target proteins to regulate cellular growth and metabolism. I propose here to study this C18:0 signaling.
To study C18:0 signaling we will exploit tools recently developed in my lab to 1) identify as complete a set as possible of proteins that are stearoylated in human and Drosophila cells, thereby characterizing the cellular 'stearylome', 2) study how stearoylation affects the molecular function of these target proteins, and thereby cellular growth and metabolism, and 3) study how stearoylation is added, and possibly removed, from target proteins.
This work will change the way we view C18:0 from simply being a metabolite to being an important dietary signaling molecule that links nutritional uptake to cellular physiology. Via unknown mechanisms, dietary C18:0 is clinically known to have special properties for cardiovascular risk. Hence this proposal, discovering how C18:0 signals to regulate cells, will have implications for both normal development and for 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: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine cardiology cardiovascular diseases
- medical and health sciences basic medicine physiology
- natural sciences chemical sciences analytical chemistry mass spectrometry
- natural sciences biological sciences biochemistry biomolecules proteins enzymes
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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.1.1. - EXCELLENT SCIENCE - 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.
ERC-COG - Consolidator Grant
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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-2016-COG
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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.
69120 Heidelberg
Germany
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