Carréno, Sébastien, Ph.D.

Research axis

• Intracellular signaling
• Mitosis
• Cancer
• Systems biology

Research description

The cytoskeleton is a diverse, multi-protein framework that plays fundamental roles in multiple biological processes with direct relevance to oncology, including cell division and motility. Generating one specific cell shape that promotes one specific biological function relies on local remodeling of the acto-myosin cortex controlled by polarization signals sent by the microtubule network. During mitosis, cells undergo a stereotyped series of shape transformations to achieve segregation of their cytoplasmic content and genomic material. The microtubule spindle separates the chromosomes, and is necessary to signal acto-myosin contractions at the metaphase plate. These equatorial contractions trigger formation of the cleavage furrow that achieves cytokinesis. This microtubule/acto-myosin crosstalk also regulates cell morphogenesis during cell motility. The microtubule array sends polarization signals that locally modify cell shape to control the directionality of migration.

Our main goal is to study how the cytoskeleton remodels the cell cortex during mitosis and migration and how impairment of these functions is implicated in carcinogenesis.

We are using functional genomics to identify the signaling networks controlling morphogenesis using RNAi gene silencing in Drosophila cells in culture combined to in vitro approaches to biochemically characterize the interplay of the identified signaling molecules. Our global strategy is to take advantage of the relative simplicity of the Drosophila genome to comprehensively identify networks important for cell division and migration. This system allows simple and efficient cellular knock-out strategies, which are hampered in mammals by the frequent functional redundancy between products of homologous and paralogous genes. We use Drosophila cells in culture as a central system with back and forth studies in human cancer cells. As the mechanisms that regulate division and migration are evolutionary conserved, discoveries made in fly are highly relevant to mammals. The strategy to integrate, in a predictive approach, what can be learned in cell division to understand cell migration and vice versa, significantly facilitates the understanding of these two critical biological functions.