Regulation of proteasomal degradation by protein phosphorylation

Increasing evidence reveal that alterations and mutations in the Ubiquitin-Proteasome System (UPS) give rise to various human diseases, most prominently cancer and neurodegenerative disorders. Thus, rescuing proteasomal defects has a huge therapeutic potential. Whilst the idea is attractive, increasing proteasome capacity remains a challenge and overcoming this challenge requires an understanding of the mechanisms regulating proteasome homeostasis. We have recently discovered that the evolutionarily conserved Mpk1 MAP kinase pathway controls proteasome assembly (Rousseau and Bertolotti, Nature, 2016). The focus of this project is to study the crosstalk between protein phosphorylation and proteasomal degradation, especially how phosphorylation adapts protein degradation to the needs. This project will use various techniques ranging from conventional biochemistry to yeast genetics and high-throughput phosphoproteomics. Both yeast and mammalian systems will be used to tackle these queries and validated candidates will be further studied in a disease context.

At the MRC PPU, we offer the possibility of two 4.5 month rotations in labs of their choice – a range of other projects from MRC PPU scientists are advertised on this website. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group. Alternatively, students can opt out of rotations and go to just one lab for a PhD.

Please send a CV with contact details of three referees to and a cover letter explaining why you have chosen to apply to MRC PPU to [Email Address Removed]..uk. The closing date for applications is March 31st, with interviews at the end of April.