Project description DEENESFRITPL Multi-level dynamics of adipocyte hypertrophy Adipocyte hypertrophy is a condition associated with larger than normal lipid droplets (LDs), the adipocyte organelles that store energy in the form of triglycerides. Adipocyte hypertrophy is irrespective of body fat and causes a wide range of pathological conditions including cardiometabolic diseases. The scope of the EU-funded SPHERES project is to investigate the hypothesis that disturbances in the interaction between LD proteins and LD lipid composition lead to adipocyte hypertrophy. Run by a multi-disciplinary network of experts, the project will develop beyond-state-of-the-art models and methods to study the formation and maintenance of large adipocyte LDs. The work will pave the way for a better understanding of the underlying mechanisms of adipocyte hypertrophy as well as the identification of therapeutic strategies targeting adipocytes. Show the project objective Hide the project objective Objective The goal of SPHERES is to understand the dynamics and consequences of adipocyte hypertrophy (enlargement) through investigation of its large lipid droplet (LD). The adipocyte LD is a unique organelle specialized in storing energy in triglycerides (TGs). Its surface is composed of a phospholipid monolayer and specific LD-associated proteins (such as perilipins, CIDEs and lipases), which jointly regulate LD stability and TG turnover. Adipocyte hypertrophy due to an increase in LD size may, irrespective of body fat mass, cause a wide range of pathological conditions, notably cardiometabolic diseases. SPHERES PIs (Langin, Rydén, Antonny) postulate that disturbances in the interactions between LD proteins and LD lipid composition lead to adipocyte hypertrophy and its deleterious consequences. We have identified three fundamental unanswered questions: what determines the unique structure and dynamics of large LD; why does increased LD size alter the functional phenotype of the adipocyte; which factors cause inter-individual variations in LD size. To address these questions, SPHERES gathers expertise in clinical and cellular studies on human adipocytes, in/ex vivo investigations in mouse models, and biophysical analyses of LDs. At the core of this application is the development of beyond-state-of-the-art models and methods (spheroid cultures, native large LD preparation and reconstitution, proximity labelling of LD proteins, gene editing in cell and mouse models, and advanced LD imaging), only achievable through joint integrated effort of the PIs and co-workers. Spanning from molecular, cellular to the whole-body level, SPHERES will link new knowledge on the formation and maintenance of large adipocyte LDs to the deleterious impact of adipocyte hypertrophy. Altogether, SPHERES has a strong potential to discover novel pathogenic mechanisms, leading to a better understanding of highly prevalent diseases and identification of therapeutic strategies targeting adipocytes. Keywords SPHERES Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-SyG - ERC Synergy Grant Call for proposal ERC-2019-SyG See other projects for this call Funding Scheme ERC-SyG - Coordinator UNIVERSITE PAUL SABATIER TOULOUSE III Net EU contribution € 3 326 680,92 Address Route de narbonne 118 31062 Toulouse cedex 9 France See on map Region Occitanie Midi-Pyrénées Haute-Garonne Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Beneficiaries (5) Sort alphabetically Sort by Net EU contribution Expand all Collapse all UNIVERSITE PAUL SABATIER TOULOUSE III France Net EU contribution € 3 326 680,92 Address Route de narbonne 118 31062 Toulouse cedex 9 See on map Region Occitanie Midi-Pyrénées Haute-Garonne Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE France Net EU contribution € 210 462,08 Address Rue de tolbiac 101 75654 Paris See on map Region Ile-de-France Ile-de-France Paris Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 KAROLINSKA INSTITUTET Sweden Net EU contribution € 3 004 881,00 Address Nobels vag 5 17177 Stockholm See on map Region Östra Sverige Stockholm Stockholms län Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,25 CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS France Net EU contribution € 3 078 793,75 Address Rue michel ange 3 75794 Paris See on map Region Ile-de-France Ile-de-France Paris Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00 Third-party Legal entity other than a subcontractor which is affiliated or legally linked to a participant. The entity carries out work under the conditions laid down in the Grant Agreement, supplies goods or provides services for the action, but did not sign the Grant Agreement. A third party abides by the rules applicable to its related participant under the Grant Agreement with regard to eligibility of costs and control of expenditure. UNIVERSITE COTE D'AZUR France Net EU contribution € 120 956,25 Address Grand chateau 28 avenue valrose 06100 Nice See on map Region Provence-Alpes-Côte d’Azur Provence-Alpes-Côte d’Azur Alpes-Maritimes Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
