PhD position in Cell Biology at Institut de Biologie de l'ENS (Paris, France) From 2 to 100 – How multiciliated cells amplify centrioles Brain ventricles, respiratory and reproductive tracts are lined by an epithelium of multiciliated cells. The collective beating of their motile cilia brushes the lumen of these organs to drive physiological fluids. Defects in the formation of motile cilia lead to severe pathological situations like hydrocephalus, irreversible lung failure and infertility. During their differentiation, multiciliated cells with only one centrosome (2 centrioles) must produce more than 100 centrioles to nucleate the same number of motile cilia1. Our aim is to decipher the molecular and cellular processes underpinning this peculiar event. We have developed a cell culture assay and single cell high resolutive imaging techniques to unveil the dynamics of centriole amplification in mouse brain multiciliated cells. We have recently revealed that this process is driven by the centrosome, and notably by the immature daughter centrosomal centriole2,3. The PhD student will contribute to characterize with sub-micrometer precision and in three dimensions the centrosomal niche giving birth to centriole amplification using state of the art imaging techniques (3D-super-resolution microscopy, correlative live imaging and focused ion beamed-scanning electron microscopy). In parallel, she/he will undertake a functional approach to identify the molecular cascade regulating massive centriole production. Beyond the fundamental aim of exploring a new functional asymmetry between centrosomal centrioles, understanding how centrioles are amplified is of particular relevance in the context of cilia-related diseases and cancer biology. 1. 2. 3. Spassky, N. & Meunier, A. The development and functions of multiciliated epithelia. Nat. Rev. Mol. Cell Biol. (2017). doi:10.1038/nrm.2017.21 Al Jord, A., Spassky, N. & Meunier, A. Centriole amplification : #DaughterCentriole. Médecine Sci. 31, 250–253 (2015). Al Jord, A. et al. Centriole amplification by mother and daughter centrioles differs in multiciliated cells. Nature 516, 104–7 (2014). The student will benefit from an interdisciplinary environment and will have access to leading edge equipment (more information on http://www.ibens.ens.fr/, https://www.univpsl.fr/en/research-centers). Applicants should send a motivation letter and a CV to : Alice Meunier [email protected] Institut de Biologie de l'ENS - Team N. Spassky "Cilia in brain development and pathology"
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