Project description
Unravelling the mechanism of nutrient sensors in catabolism
Catabolism is a process that breaks down large molecules into smaller units that are either oxidised to release energy or used in other anabolic reactions. The mechanism that catabolic nutrient sensors use to synchronise catabolic activities is still not completely understood. The EU-funded MetaboSENS project will explore the role of class III PI 3-kinase – the only PI 3-kinase expressed in all eukaryotic cells – in catabolic homeostasis. The focus will be on studying the enzyme functions involved in metabolic adaptation to fasting and mitochondrial activity. The new mechanisms that will be discovered may provide biological targets that will be tested in pre-clinical models.
Objective
Nutrient sensing enables metabolic homeostasis by matching energy use with fuel availability. The vast body of knowledge on pro-anabolic nutrient sensors, such as insulin and class 1 phosphoinositol-3 kinase (PI3K) signalling exposed the missing links in molecular coordination of catabolism. The cellular catabolism relies on mitochondrial activities and on lysosomal pathway of autophagy, both paced by the biological clock. However, how pro-catabolic nutrient sensors synchronize these catabolic activities is not well understood. We discovered that class 3 PI3K, the only PI3K present in all eukaryotes, is essential for catabolic homeostasis in vivo, but the mechanisms of its metabolic functions are still lacking. We found novel roles for class 3 PI3K in metabolic adaptation to fasting and mitochondrial activity, beyond its established functions in autophagy and endosomal trafficking. These findings form the basis of our innovative interdisciplinary research program that will investigate the molecular bases of Metabolic integration in vivo by a nutrient SENSing pathway of class 3 PI3K (MetaboSENS). In the MetaboSENS research program, we seek to identify transcription factor networks and regulatory complexes of class 3 PI3K that serve its catabolic integrator function. We aim to reveal the physiological oscillation of class 3 PI3K signalling and its reciprocal impact on metabolic timekeeping. Finally, the MetaboSENS project will combine patient analyses and the medical expertise of my team to reveal, for the first time, genetic alterations in class 3 PI3K signalling in inborn metabolic disease. The new mechanisms that we discover may provide therapeutic targets that we will test in the pre-clinical models. Altogether, the MetaboSENS project will redefine our view of systemic catabolism.
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.
- engineering and technology electrical engineering, electronic engineering, information engineering electronic engineering sensors
- engineering and technology environmental engineering energy and fuels
- 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.1.1. - 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-2018-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.
75654 PARIS
France
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.