Structure-based approaches for ubiquitin specific protease functional analysis and drug discovery

Ubiquitin specific proteases are key regulators of cellular protein degradation, DNA damage repair and cell cycle control and are often deregulated in human cancers (1). They are therefore considered promising new drug targets. Our research seeks to better understand their structure, function and specificity (2, 3) and to identify specific inhibitors for these proteases.
In this project we will use structural biology techniques in combination with ligand binding and enzymatic assays to discover novel binding sites in these proteases that could be targeted by drug molecules. Furthermore crystal structures in complex with inhibitors will shed light onto how these could be modified for improved specificity. These structural insights into the molecular interactions with binding partners and inhibitors will reveal fundamental principles of ubiquitin deconjugation, the molecular basis of signalling pathways implicated in disease processes and will be vital for the development of novel therapeutic agents targeting these enzymes. The project will provide training in a wide range of molecular biology, biochemical and structural biology techniques (including cloning, protein expression, enzymology and X-ray crystallography). You will be part of an international group based in the interdisciplinary Centre for Biomolecular Sciences on University Park campus in Nottingham, benefiting from a diverse and stimulating research environment. Interested applicants are welcome to submit informal enquiries to [Email Address Removed].