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MetaboSENS SIGNED

Metabolic integration by nutrient SENSing

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EC-Contrib. €

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Project "MetaboSENS" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 1˙999˙391 €
 EC max contribution 1˙999˙391 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2018-COG
 Funding Scheme ERC-COG
 Starting year 2019
 Duration (year-month-day) from 2019-11-01   to  2024-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 1˙999˙391.00

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 Project 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.

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