Cellular identities can be modulated by external factors, such as chemical/hormonal signals or physical cues from the environment such as mechanical constraints. Interestingly, not all cells respond to stimuli in the same way, implying the mechanical induction of distinct cellular identities by integrated signals still to be discovered. The collaboration between biochemists, cell biologists and biophysicists within Who am I? aims at developing new devices and quantitative methods for analyzing and modeling these events.
Scaffolding extracellular signals to modulate nuclear functions.
Signaling pathways, initially described for cytosolic signals, may actually function as important epigenetic modulators when appropriately reoriented to nuclear compartments. Therefore the current simplified view of linear cascades needs to be re-evaluated in light of the growing evidence of supra-molecular complexes (signalosomes) built around specialized scaffolding proteins (e.g. beta-arrestins), which regulate subcellular localization, nuclear shuttling and signal dynamics between pathways.
Who am I? teams have led pioneering work in these fields and will investigate the mechanisms connecting receptors to signaling scaffolds and to transcriptional regulation in both cell and animal models by a multidisciplinary approach combining dynamic investigation of subcellular compartments, biophysical study of protein-protein interaction, interactive computational modelization, advanced fluorescence imaging as well genetic and epigenetic analysis.
Influence of mechanical cues on cell fate, gene expression and tissue organization
The ability of cells to actively sense and respond to environmental mechanical signals has dramatic effects on many cell decisions, including adhesion, polarization, migration, division and cell differentiation. A key issue is the understanding of the collective behavior of cells and its implications for tissue organization, but also tissue development and wound healing, in both normal and pathological contexts. The Who am I? teams will focus on determining the physical and biological stimuli controlling collective movement of cell assemblies, on the processes of cell invasion into conjunctive tissue, on the cohesion of cell aggregates, and on the mechanisms responsible for the phenotypic changes in tumors compared to normal cells.