The Rousseau lab is interested in decoding how protein degradation by the proteasome is regulated in cells so that accumulation of unfolded, misfolded, or damaged proteins can be cleared before they become deleterious. The proteasome recognises, unfolds, and degrades faulty proteins that have been tagged with ubiquitin to maintain the integrity of the proteome. Defects in the proteasome give rise to various human diseases, such as cancer and neurodegenerative disorders. We recently reported that proteasome assembly and activity is increased upon various stresses to help rewire the proteome and survive (Rousseau lab). We now study the spatio-temporal regulation of proteasome assembly and activity in health, stress and diseases using both yeast and mammalian systems. This includes assembly of the poorly characterised alternative forms of the proteasome. The PhD project aims at engineering the proteasome to develop new technologies to monitor assembly of its alternative forms suitable for high-throughput screening. This will be instrumental in better understanding the function of alternative forms of the proteasomes and will help understand their involvement in diseases. The project will offer training opportunities in state-of-the-art technologies such as cell engineering (CRISPR-Cas9 gene editing of proteasome genes), molecular biology (proteasome and protein degradation assays), and high-resolution confocal microscopy (proteasome dynamics). 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 here. Rotations provide valuable experience and help with deciding on the choice of PhD project and research group. To apply for this project, or any of our other PhD projects, please complete the following applicationAPPLY NOWWhen completing the application, there will be space to copy over your CV, contact details of three referees and a cover letter explaining why you have chosen to apply to MRC PPU. The closing date for applications is 31st October 2024. Applications from overseas students are welcome.If you have any questions or need to get in touch with us, please email us at [email protected].