Description of the thesis topic

Mitosis is a fundamental process required for generating multicellular organisms, for tissue renewal and homeostasis. During development, both the orientation of the division plane and the timing of mitotic entry fundamentally influence the positioning of daughter cells and their organization into tissues. However, the mechanisms that control the timing of mitotic entry remain poorly understood. Entry into mitosis is triggered by the activation of a mitotic kinase cascade, including the kinases Aurora A and Plk1, and the simultaneous inactivation of counteracting phosphatases. During development, how does the regulation and cross-talk between mitotic kinases and opposing phosphatases ensure timely mitotic entry? How does the deregulation of this cross-talk contribute to cancer formation?
Over the last few years, our team has contributed to identifying the molecular mechanisms that lead to the activation of mitotic kinases, particularly identifying a new mode of activation of the Aurora A kinase1-6. The molecular description of these mechanisms now offers the opportunity to study them in a developmental context to determine how an acceleration or delay of entry into mitosis impacts development. In this context, the candidate will use a combination of genetics and cell biology approaches in the nematode C. elegans to decipher the activation mechanisms of mitotic kinases to understand how the regulation of these kinases impacts the time of entry into mitosis and embryonic development.

References [1-6] : Tavernier, N. et al. J Cell Biol 208(6), 661-669 (2015) ; Thomas, Y. et al. Cell Rep 15(3), 510-518 (2016); Vigneron, S. et al. Dev Cell 45(5), 637-650.e7 (2018), Tavernier, N. et al. J Cell Biol 220(9), (2021), Tavernier, N. et al. Nat Commun 12(1), 1899 (2021), Nkombo Nkoula, S. et al. Sci Adv 9(29), eadf7826 (2023)

Work Context

The Institut Jacques Monod (IJM) (https://www.ijm.fr/), located on the Grands Moulins campus of the University of Paris Cité (75013 Paris), is a center of excellence in fundamental biology with 26 research teams and cutting-edge technological platforms in imaging (Imagoseine) and proteomics (Protéoseine). The host team, led by Lionel Pintard, comprises eight members, including permanent staff.