Molecular dissection of the pathways linking ribosome biogenesis, the nucleolar stress response and oncogenesis

Ribosome biogenesis is a fundamental cellular process that is inextricably linked to cell growth, proliferation and oncogenesis. Further, the site of ribosome assembly, the nucleolus, acts as a key stress sensor, where many cellular stresses converge and act to trigger p53 stabilisation. The molecular mechanisms linking and regulating these processes, however, remains largely uncharacterised.

I will investigate the links between these processes through the dissection of GLTSCR2, one of the few factors that has been directly implicated in each of these pathways. My first goal is to uncouple the functions of GLTSCR2 in each pathway. The dissection of GLTSCR2s function is possible as it interacts with key factors from each pathway. We aim to precisely map the nature of these interactions which will provide the foundation upon which to generate specific mutants of GLTSCR2. We will then establish an in vivo system where the mutant forms of GLTSCR2 can be analysed.

Our study will allow the multiple facets of GLTSCR2 biology to be explored and provide a base for understanding and analysing disease-linked mutations, shedding light on the overlapping nature of these fundamental processes.