Romain Levayer, head of the unit “Cell death and epithelial homeostasis” was awarded a European Research Council (ERC) Consolidator grant for his project ‘PrApEDoC – Predicting Apoptosis Engagement Downstream of Caspases in vivo’. Romain Levayer is among the 321 researchers in Europe (and 41 in France) to receive this prestigious and highly selective grant in 2022.
The team of Romain Levayer studies how cell death contributes to the dynamics of epithelial tissues, either during embryonic development, or to guarantee their homeostasis and their capacity to cope with external perturbations. They focus their investigation on the role of effector caspases to induce apoptosis. Effector caspase activation was long thought to be a terminal point of no return that definitely engages cell in apoptosis. However, recent observations suggest that their activation does not lead systematically to cell death. Yet, we know very little about the parameters that set for a specific cell the decision to die or not die downstream of effector caspase activation. With this new project, the team of Romain Levayer will for the first time identify parameters that can modulate apoptosis engagement following caspase activation in vivo. They will combine quantitative live imaging of effector caspase sensors combined with direct modulation of caspase by optogenetics to build the first quantitative characterisation of the relationship between effector caspase activation and apoptosis engagement in vivo at the single cell level. They will screen for new pathways that can modulate the sensitivity to caspases and the susceptibility to engage in apoptosis. The project funded by the ERC will help to understand how differential sensitivity to effector caspases can tune the spatio-temporal distribution cell death issue and help to understand processes of clonal selection during development and cancer progression.