Regulation of protein degradation and homeostasis by the ubiquitin system

Protein degradation is a fundamental process that is important for timely elimination of damaged proteins. This process relies on modification of proteins with ubiquitin, a signal to target destruction of modified proteins. Ubiquitylation is a very dynamic process and ubiquitin signals are removed/edited by deubiquitinating enzymes (DUBs). Failure to eliminate damaged/misfolded proteins is an underlying cause of age-related diseases such as Alzheimer’s and Parkinson’s disease. In the lab, we employ a range of techniques including biochemical approaches, state-of-the-art proteomics, structural biology and mouse models to elucidate new layers of control in protein degradation, research that will advance our understanding of neurodegenerative diseases.

We recently discovered a new family of DUBs that regulate protein degradation signals. The available projects build on our exciting, unpublished findings that these DUBs are novel regulators of protein homeostasis. In this PhD project, you will use innovative genetic and cell biology techniques to dissect how MINDY DUBs control protein degradation. Specifically, you will address how protein degradation is regulated in different subcellular compartments. This project has the potential to unravel novel pathways modulating protein homeostasis, and how these can be manipulated in neurodegenerative diseases.