MRC Funded
Project with
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 (Rousseau et al., Nature, 2016). This involves the transport of proteasome assembly chaperone (PAC) mRNAs along actin structures and their relocalisation to a specific subcellular localisation upon stress to stimulate their translation (Williams et al., Nature Cell Biology, 2022). The goal of this project is to define how actin remodelling controls PAC mRNA translation and cell survival. The project will offer training opportunities in state-of-the-art technologies such as live-cell mRNA tracking using confocal microscopy, mRNA pull-down followed by proteomics and CRISPR/Cas9 genome editing.