Team TCCD - Translation, Cell Cycle and Development

Our research investigates how translation mechanisms and kinase signaling drive cell cycle regulation and development, spanning studies from marine metazoans to human cells. Our approach involves multi-scale analysis: from the structural and biochemical scale to the cellular and developmental/whole organism levels. 

Translation and cell cycle at the egg-to-embryo transition in sea urchin 

Axis leaders : Julia Morales, Fernando Roch

mRNA translation is a key step in the regulation of gene expression, allowing rapid and precise adjustment of the cell to physiological and pathological variations. The early development of sea urchin embryos is an interesting and relevant model for the study of translational control, as  fertilization triggers a rapid increase in protein synthesis, necessary for the first mitotic divisions of the embryo. This increase in protein synthesis activity is independent of any new transcription and relies on maternal mRNA recruitment. Gametes are easy to obtain in large quantities, allowing for molecular, biochemical and cellular approaches. By a combination of cellular and molecular approaches, we analyze translation factors, mRNA recruitment into polysomes, and signalling pathways regulating the egg-to-embryo transition in the sea urchin Paracentrotus lividus and Sphaerechinus granularis

Control of global protein synthesis during kidney regeneration of catshark

Axis leader: Agnès Boutet

During embryogenesis nephrons, the functional units of kidneys, are derived from a pool of self-renewing progenitors that cease propagation and are terminally differentiated within few days after birth in mammals.  In contrast, new nephrons are continually added to the adult kidney of sharks and this process contributes to the lifelong kidney growth in this taxon. Regenerative property  of the sharks› kidney is also observed upon partial nephrectomy, indicating that the aptitude to growth new nephrons can be triggered in a pathological context. This interesting property relies on the maintenance of the nephron progenitor pool beyond hatching. We are interested in understanding the physiological and molecular mechanism associated to the maintenance of the nephron progenitors in the small-spotted catshark (Scyliorhinus canicula),  at the post-embryonic stage.  In particular, we are studying the role of global protein synthesis control in this maintenance together with the one of the mTOR pathway, an important signalisation pathway involved in translation initiation.

Mitotic kinases: from fundamental biology to therapeutic opportunities   

Axis leader : Sandrine Ruchaud

Our general interest lies in analyzing the molecular mechanisms that orchestrate the smooth progression of cell division. Chromosome bi-orientation, segregation into the two future daughter cells and cytokinesis are essential steps in ensuring the fidelity of the process, and must be finely regulated. Their coordination is tightly controlled by protein kinases whose expression/activity is deregulated in many cancers. Errors in these steps can also lead to aneuploidy, predisposing cells to cancerous transformation. We study the biological functions and inter-regulation of some of these protein kinases (notably Aurora B and Haspin), in order to gain a better understanding of their mechanisms of action and use this knowledge to design new targeted anti-cancer therapies (marine origin, bio-inspired and/or synthetic).

Function and regulation of protein kinase CDK10/CycQ

Axis leader: Pierre Colas

CDK10 has long remained one of the most mysterious CDKs (cyclin-dependent kinases), in the absence of a known activating cyclin. We identified an activating cyclin (CycM, recently renamed Q), revealed the kinase activity of CDK10/CycQ, unveiled its role in the control of ETS2 stability and in ciliogenesis. We established the first etiological basis of STAR syndrome caused by CycQ mutations, and we contributed to the description of a new syndrome (Al Kaissi) caused by CDK10 mutations. We study the functions of CDK10 / CycQ by : i) the identification of interaction partners of CDK10 and CycQ; ii) the functional characterization of CDK10 and CycQ variants involved in Al Kaissi and STAR syndromes; iii) biological chemistry approach, aiming to selectively inhibit CDK10 by small chemical molecules (iv) knockout of the CDK10 gene by CRISPR in immortalized human cells.