About the Project
Ubiquitylation represents a major post-translational modification that controls numerous cellular processes. In the course of our research studies into Parkinson’s disease mechanisms, we discovered that ubiquitin itself can be modified by phosphorylation. In mammalian systems the PINK1 kinase phosphorylates ubiquitin at residue Serine65 (Ser65) and this Ser65 -Phospho-ubiquitin functions as a chemical messenger to activate the Parkinson’s ubiquitin ligase, Parkin. Global mass spectrometry screens have provided evidence that ubiquitin can be phosphorylated at other residues in cells and tissues derived from various human cancers. The regulation of these other Phospho-ubiquitin species including the identity of their upstream kinases is unknown and their significance in human disease states unclear. The development of tools is a critical next step and we have recently generated state-of- the-art phospho-specific antibodies against all known ubiquitin phosphorylation sites (Thr7, Thr12, Thr14, Ser20, Ser57, Tyr59, Ser65 and Thr66).
The project seeks to determine the biological role of these Phospho-ubiquitin species in cells. Specifically we will deploy these anti-Phospho-ubiquitin antibodies in cells stimulated by diverse stimuli including growth factor stimulation, mitogen activation and DNA-damaging induced stimuli. cellular studies to better understand their regulation in signalling pathways linked to cancer. Where a specific stimulus is identified to induce Phospho- ubiquitin, appropriate follow-up studies will be undertaken to define the regulatory mechanism including the identification of the kinase. The project will also involve a collaboration with the Tayside Biorepository to validate the role of specific Phospho- ubiquitin species in cells and tissues derived from various cancers.
Please see our website for further details and how to apply - https://www.dundee.ac.uk/study/pgr/life-sciences-msc-research/
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