Reference : PhD Manuel Mendoza
Asymmetric cell division is a key strategy to generate cellular diversity during the development of organisms. Nuclear pore complexes (NPCs) mediate communication between the nucleus and the cytoplasm, and also regulate gene nuclear position and expression through interactions with chromatin. Interestingly, the acquisition of cellular identity is coupled to changes in NPC composition, but whether and how these changes determine cell fate remains unclear.
We recently discovered that modulation of NPCs by lysine deacetylation leads to establishment of cell identity in budding yeast daughter cells, through regulation of both nucleo-cytoplasmic transport and gene positioning. Thus, NPC deacetylation is a differentiation switch in asymmetrically dividing budding yeast, raising the possibility that similar mechanisms might establish cell identity in animal cells. The student in charge of this project will help characterize how NPC deacetylation leads to cell fate specification, and shapes nuclear transport and three-dimensional nuclear organization.Characterizationofthis new cell fate establishment mechanism will reveal novel principles of animal stem cell self-renewal and tissue homeostasis, and of human pathologies associated with defects in these processes, including microcephaly and cancer.
Date limite de candidature : 1 novembre 2018