Recent years have seen major progress towards the understanding of function of centrosome, an organelle acting as the major organizer of microtubule arrays. Furthermore, previously unexpected links between centrosome anomalies and a plethora of human diseases and developmental defects have been uncovered. This in turn raises the prospect of exploiting centrosome-related pathways for therapeutic applications. Moreover, recent evidence from in vivo models (fly, mice) strongly suggests a context-dependent role for a centrosome in proliferation and differentiation. Hence, this raises an intriguing possibility of cell type-specific requirements for a correct number of centrosomes during their proliferation and terminal differentiation. However, our current understanding of the role of centrosome in such processes is surprisingly sparse.
Embryonic stem cells (ESCs) have the ability of unlimited proliferation, and can differentiate into any cell type of interest. Moreover, recent technological development has enabled to efficiently utilize methods of stable transgene expression or RNA interference also in human ESCs. These features make them very suitable candidates to study the function of centrosome in proliferation and differentiation, in the context of non-transformed human cells.
In this proposal I will use hESCs to study the function of centrosome and impact of its numerical anomalies on proliferation and cell differentiation. I believe the proposed project has potential to set a new ground in research pursuing functional aspects of centrosome biology.