Biomolecular Science and Medicinal Chemistry Division PhD project: Proteases in the ubiquitin system – from molecular mechanisms to the development of novel inhibitors

Ubiquitin is a posttranslational modifier that tags substrate proteins for degradation and regulates virtually all known cellular processes. Ubiquitination is reversible and the human genome encodes 56 ubiquitin specific proteases (USPs) as the largest family of deubiquitinating enzymes that can cleave ubiquitin from modified proteins and thus salvage them from destruction by the proteasome. Members of the USP family are often dysregulated in disease processes and have therefore been identified as promising drug targets in cancer, infectious diseases and neurodegenerative disorders 1. Hence, USP inhibitor discovery is a highly active area of research 2. How these multi-domain cysteine proteases specifically recognise their substrates and thus exert their regulatory function is poorly understood. We have launched a divisional research programme that brings together our expertise in synthetic medicinal and computational chemistry, structural biology and biomolecular sciences in order to advance our molecular understanding of the structure, function and specificity of USPs and to identify and evaluate inhibitors for the benefit of developing novel therapeutic agents.

This project will transcend disciplinary boundaries and be led by a supervisory team of three academics with different backgrounds reflecting the unique strengths of the Biomolecular Science and Medicinal Chemistry Division in the School of Pharmacy (https://www.nottingham.ac.uk/pharmacy/research/divisions/biomolecular-science-and-medicinal-chemistry/index.aspx.). Being part of this programme will equip you with highly sought-after multidisciplinary skills in the biomedical research area.

You will be located on University Park campus in Nottingham, benefiting from a diverse and stimulating research environment. Please address any informal enquiries to [Email Address Removed]. We will be happy to answer queries from interested applicants and provide more information.