Signalling pathways controlling protein degradation upon stress

Increasing evidence shows that alterations and mutations in the UPS give rise to various human diseases, such as cancer and neurodegenerative disorders. Our interest is to understand how the activity of the ubiquitin-proteasome system is regulated in cells so that accumulation of unfolded, misfolded, or damaged proteins can be cleared before they become deleterious. We recently reported that proteasomal degradation is regulated upon proteotoxic stresses in a phosphorylation-dependent manner (Rousseau and Bertolotti, 2016, Nature). The new project will focus on how protein phosphorylation events regulate protein homeostasis and cell survival. An additional project consists in developing new tools to characterize how proteasome homeostasis is regulated in cells, and to use these tools to identify new regulators and drugs modulating proteasomal degradation. Both yeast and mammalian systems will be used for this project.

At the MRC PPU, as well as the possibility of a PhD in one particular lab, 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.

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 the first round of applications is December 31st, with interviews in February.