Identification of Novel Ubiquitin-Dependent Mechanisms Involved in Cell Signaling

The post-translational modification Ubiquitin regulates most cellular processes including transcription, DNA repair and the cell cycle by modulating the fate and function of proteins. Ubiquitin is conjugated onto one or more lysine residues of a protein target through a cascade of enzymatic reactions which culminates in the covalent attachment of one (i.e. monoubiquitylation) or multiple (i.e. polyubiquitylation) ubiquitin molecules. It is estimated that the human genome encodes as many as 600 E3 ubiquitin ligases and around 90 deubiquitylases which together tightly control protein ubiquitylation. The further characterisation of these enzymes, in terms of the molecular mechanisms and cellular processes which they regulate, could potentially lead to the identification of novel drug targets relevant for human diseases including cancer and neuropathies.
The project will focus on characterising recently identified interactors and potential substrates of E3 ligases and deubiquitylases in their cellular context using molecular and cellular biology techniques (siRNA, confocal microscopy) as well as biochemical/biophysical techniques (protein purification, binding studies). The project will benefit from world-class bioimaging facilities available at the University of Bath as well as ongoing collaborations within and outside the department of Biology and Biochemistry. The successful candidate will be involved in a very exiting area of research and will have the opportunity to make novel contributions to the field of ubiquitin signaling.