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).

References

1: Adrien Rousseau and Anne Bertolotti. Regulation of proteasome assembly and activity in health and disease. Nat Rev Mol Cell Biol (2018), 19, 697–712

2: Adrien Rousseau and Anne Bertolotti. An evolutionarily conserved pathway controls proteasome homeostasis. Nature (2016), Nature 536, 184–189.

3: Thomas Williams, Roberta Cacioppo, Alexander Agrotis, Ailsa Black, Houjiang Zhou and Adrien Rousseau. Actin remodelling controls proteasome homeostasis upon stress. Nat Cell Biol 24, 1077–1087 (2022).

4: Ailsa Black, Thomas Williams, Houjiang Zhou and Adrien Rousseau. The ribosome-associated chaperone Zuo1 controls translation upon TORC1 inhibition. EMBO Journal, (2023).

5: Thomas David Williams, Aurellia Ramara and Adrien Rousseau. Proteasome Assembly Chaperone Translation Upon Stress Requires Ede1 Phase Separation at the Plasma Membrane. iScience, (2023).