SATBIOFUN · Genome editing for spatiotemporal analysis of centriolar SATellite BIOgenesis and FUNction in cellular stress responses

Genome editing for spatiotemporal analysis of centriolar SATellite BIOgenesis and FUNction in cellular stress responses

Cells contain specialized structures that perform a range of functions essential to maintaining the health of the cell. Defects in these structures or their function can manifest in a disease state. Understanding how these structures contribute to the maintenance of a healthy state allows us to learn how diseases arise and develop strategies to prevent or treat them. One such structure is the centrosome. The centrosome contributes to a number of cellular processes and serves as the base of the primary cilium, an antenna-like structure that allows cells to respond to external stimuli. Around the centrosome lie a number of protein-containing granules, termed centriolar satellites. These are involved in the movement of proteins and are crucial for normal centrosome and cilium assembly and function. Currently little is known about the full role, composition, or regulation of satellites, although mutations in genes encoding satellite proteins result in human diseases, such as ciliopathies and neurological disorders. The central scientific goal of this project was to expand our knowledge with regard to satellite function and contribution to maintaining a disease-free state. The realization of this goal was achieved through a number of specific objectives, namely: the generation of a unique toolbox of reagents with which to study satellites; profiling of satellite protein contribution to normal satellite function; and the definition of the contribution of satellites to cell stress responses. Furthering our understanding of satellites function enhances our knowledge of how their dysregulation may lead to disease. To achieve these objectives, we used genome-editing and cutting-edge imaging techniques. This allowed us to define a novel function for satellites in the cellular response to proteostatic stress, thereby identifying a previously unexplored link between the centrosome and proteostasis fields. In realizing our objectives, the Fellow received extensive training in a range of state-of-the-art techniques during an Outgoing Phase in Canada. The Return Phase in Ireland allowed the transfer of this knowledge to Europe, and in doing so enhanced the European research environment. The Fellow also acquired a range of complementary skills, allowing the fulfillment of the overarching objective of developing the Fellow’s career to a position of professional maturity and facilitating the goal of establishing her own independent research group.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз