Benoit Ladoux awarded an ERC Advanced Grant 2020 !
The European Research Council has today announced the winners of its 2020 Advanced Grants competition. The funding will go to 209 leading researchers across Europe (21 in France). ERC Advanced Grants support excellent researchers at the career stage at which they are already established research leaders with a recognised track-record of research achievements. The Institute Jacques Monod (CNRS / University of Paris) warmly congratulates Benoit Ladoux and is delighted with this first ERC Advanced Grant awarded by a member of the Institute!
Benoit Ladoux (Research Director CNRS) is a physicist by training, working on cell mechanics. Starting in the single molecule field, he developed a research activity in cell mechanics and adhesion as a PI in the laboratory Matière et Systèmes Complexes. In 2008, he was involved in the creation of the Mechanobiology Institute (MBI) directed by MP. Sheetz in Singapore. He obtained a full professorship position in the Physics Department of Paris Diderot University in 2010. After spending two years in Singapore between 2010 and 2012, he came back to Paris and joined a biological Institute, the Institut Jacques Monod as a senior group leader together with a cell biologist, RM. Mège. In 2015, he moved from a faculty position to the CNRS as a research director.
From 2012 to 2018, he shared his time between Paris and Singapore. His research aims at understanding how cell-adhesion mechanisms are associated to mechanotransduction and driven by the mechanical properties of the cellular environment and how mechanosensing regulates cell behaviors and tissue homeostasis. He developed various tools to analyze the mechanical responses of cells to the physical properties of the environment including rigidity and topography sensing. For instance, his team established that actin cytoskeleton can serve as a large scale mechanosensing machinery in response to substrate stiffness by adapting its polarization. He studied the impact of substrate geometry, confinement, curvature on collective cell migration. His recent research focused on the impact of mechanics on epithelial homeostasis including cell proliferation and cell extrusion.
He was a member of the Institut Universitaire de France (2011-2015) and received the Pierre-Gilles de Gennes Award (2014). He was awarded an ERC consolidator grant (2014) followed by an ERC Proof of Concept (2019). He was the coordinator of multiple research programs including Human Frontier Science Program (2012), ANR (2005, 2010, 2012), Ligue contre le Cancer, USPC-NUS program.
The DeadOrAlive Project
Epithelia are assemblies of multiple cells whose complex dynamic behavior relies on physical properties including jamming-unjamming mechanisms, active turbulence and active nematic principles. The homeostasis of epithelia is crucial to maintain barrier function and integrity while epithelial cells are constantly challenged by the environment. To face these challenges, epithelia are dynamics and have to deal constantly with cell renewal and apoptotic extrusion, whose balance is key for epithelia homeostasis. On top of this role in tissue homeostasis, cell extrusion is a major cause of tissue shape changes and tumor progression. Extrusion mechanisms can thus lead to different cell fates namely dead or live cells but the factors selecting different cell fates are unknown. Extruding cells and their neighbors experience various mechanical stresses that lead to cell shape changes and could determine the way cells are extruded and their fate. However, these mechanical stresses and their impact on tissue organization remain to be determined.
From our recent study on emergent active nematic properties of epithelia, we hypothesize that mechanical constraints coming from the active forces generated by neighboring cells and the passive physical properties of the environment can determine the modes of cell extrusion and the fate of extruded cells.
Here we propose to tackle the molecular mechanisms and physical principles that determine the manner by which cells are extruded and the collective response of surrounding cells, and to evaluate their contribution in tissue homeostasis, morphogenesis and tumor progression. By combining tools from soft matter physics, cell biology and engineering, our project will reveal how active and passive physical signals are overarching components of the behaviors of tissue at different temporal and spatial scales, and may further establish novel paths to understand the mechanobiology of epithelial tissues in normal and pathological conditions.