SPHERES - Lipid droplet hypertrophy : the link between adipocyte dysfunction and cardiometabolic diseases

Project description

SPHERES is a 7 years project (2020-2027) funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (Grant Agreement N°856404). It gathers 3 principal investigators:

  • Dominique Langin, Professor at Toulouse III – Paul Sabatier University ,
  • Mikael Rydén, Professor of Clinical and Exprimental Fat Tissue Research at the Department of Medicine, Karolinska Institutet and
  • Bruno Antonny, Research Director at the Institute of Molecular and Cellular Pharmacology, CNRS.

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.

Principal Investigators

Dominique Langin - Toulouse III - Paul Sabatier University (UT3)
  • Trained as a veterinarian (DVM), Dominique Langin obtained MSc and PhD degrees in France and did post-doctoral training at the University of Lund, Sweden prior to embracing a scientist career at INRAE, CNRS and Inserm. In 2006, he was recruited at Toulouse III - Paul Sabatier University and Toulouse University Hospitals as University Professor and Hospital Practitioner. Besides teaching and hospital duties, Dominique Langin devotes most of his time to research. Within the Institute of Metabolic and Cardiovascular Diseases (I2MC) which he is the Director since 2021, his team has been working on adipose tissue and fat metabolism in the context of obesity and metabolic complications. The research has been translational combining molecular, cellular, animal and human studies with participation in several European projects.

About the Host Institution
  • With its roots dating back to the 13th century, Toulouse III - Paul Sabatier University was officially founded in 1969 following the merger of the faculties of medicine, pharmacy and science. The diversity of its laboratories and the quality of its courses in the fields of science, health, sport, technology and engineering have guaranteed its scientific influence over the last fifty years and have made it one of the best universities in the world. In 2020, it was ranked among the 300 best establishments for scientific performance in the international ARWU ranking.

MIkael Rydén - Karolinska Institutet (KI)
  • Mikael Rydén is professor of clinical and experimental adipose tissue research and senior consultant in Endocrinology/Diabetology and Internal Medicine. He obtained his PhD-degree at KI in 1997 within the area of molecular neurobiology and he has a deep understanding of cell and molecular biology. Following a 2-year post-doctoral period at the Department of Medicine (H7) at KI, he switched his research focus to adipose tissue research. He currently heads a translational research group of ~20 people. They have a large clinical research facility integrated with the outpatient clinic at Karolinska University Hospital, Huddinge and a fully equipped wet laboratory.

About the Host Institution
  • Karolinska Institutet is one of the world’s leading medical universities. Their vision is to advance knowledge about life and strive towards better health for all. Karolinska Institutet accounts for the single largest share of all academic medical research conducted in Sweden and offers the country’s broadest range of education in medicine and health sciences. The Nobel Assembly at Karolinska Institutet selects the Nobel laureates in Physiology or Medicine.
Bruno Antonny - The French National Centre for Scientific Research (CNRS)
  • Bruno Antonny is a biochemist and biophysicist. After a PhD on phototransduction with M Chabre (1992) and a first position at the CNRS (1994), he moved to the Schekman lab at UC Berkeley in 1999 where he studied the dynamics of the COPII coat. He started his lab in 2002 to study molecular mechanisms that allow cells to change the shape and composition of their membranes. His lab has made three discoveries: (i) membrane curvature is cellular information and controls in space and time biochemical reactions (e.g. Bigay et al 2003 Nature); (ii) Cells use the metabolic energy of PI4P to transport lipids in a directional manner (Mesmin et al 2013 Cell); (iii) polyunsaturated lipids adapt their shape to mechanical stress, thereby facilitating membrane deformation/fission (Pinot et al. 2014 Science). With a support from an ERC advanced grant in 2010, his team has expanded and now combines expertise in biochemical reconstitution, cell biology and molecular dynamics simulations to studying membrane biology mechanisms at molecular and cellular scales.

About the Host Institution
  • The French National Centre for Scientific Research is among the world's leading research institutions. Its scientists explore the living world, matter, the Universe, and the functioning of human societies in order to meet the major challenges of today and tomorrow. Internationally recognised for the excellence of its scientific research, the CNRS is a reference in the world of research and development, as well as for the general public.

ERC Synergy Grants

Synergy Grants are awarded to minimum 2 to maximum 4 Principal Investigators (PIs) and their teams. They must demonstrate the ground-breaking nature, ambition and feasibility of their scientific proposal. PIs must also demonstrate the added value and the complementary of their team, in terms of skills, knowledge, methods, expertise, to address the scope and complexity of the proposed research question. Applicant PIs therefore must demonstrate that only with the added value of the synergetic team could the proposed research lead to breakthroughs that would not be possible by the individual PIs working alone.

The European Research Council, set up by the EU in 2007, is the premiere European funding organisation for excellent frontier research. Every year, it selects and funds the very best, creative researchers of any nationality and age, to run projects based in Europe. The ERC offers four core grant schemes: Starting, Consolidator, Advanced and Synergy Grants. With its additional Proof of Concept grant scheme, the ERC helps grantees to bridge the gap between grantees’ pioneering research and early phases of its commercialisation.

Find more about H2020 Programme here.