A nuclear envelope regulator of ageing

The nuclear envelope forms the boundary between the genetic material and the rest of the cell, but has much wider functions in regulation of structure, transport and integrated signalling pathways than such a simple boundary function implies. A role for the nuclear envelope in cellular senescence and organismal ageing is exemplified by the dramatic and tragic premature ageing condition, Hutchinson-Gilford Progeria Syndrome, in which a failure to process a lamina protein to a soluble mature form has myriad consequences on nuclear structure, gene expression and cellular functioning. This project will build on recent results from the lab that connected this molecular pathology with normal ageing processes, and uncovered details of the progressive altered gene expression patterns coupled to metabolic changes that are the hallmarks of cellular senescence.
The project will involve proteomic and biochemical characterisation of the post-translational modifications (proteolytic cleavage, phosphorylation) key to this process, together with cell biological approaches to understand the signalling pathways involved. This project will run in parallel with on-going studies in the lab on the normal physiological regulation of nuclear envelope structures and will involve training in proteomics, bioinformatics and state-of-the-art imaging techniques at the light and electron microscope level, including novel techniques for following nascent phospholipid trafficking.