Protein degradation by the Ubiquitin-Proteasome System (UPS) is essential to maintain cellular homeostasis and dysregulation in components of the UPS leads to age-related diseases. E3 ubiquitin ligases are key components of the UPS, transferring ubiquitin from a loaded E2-conjugating enzyme and onto lysines of a protein substrate. Therefore, understanding how these enzymes function at the molecular level is important for our fundamental understanding of protein degradation and also because E3s have a strong potential as novel drug targets.
1. Define the biochemical and structural properties of HECT E3 ubiquitin ligases.
Lee Harris, ARUK-funded PhD student
Collaboration with Dr John Burke, University of Victoria, Canada; Professor Benedikt Kessler, University of Oxford; Dr Eric Strieiter; Dr Farid El-Oualid, UbiQ; Dr Satpal Virdee, MRC-PPU university of Dundee
2. Determine the role and function of HECT E3 ubiquitin ligases in the Brain.
Sarah Jasem (Kuwait Science Scholarship, 2015-2019)
Collaboration with Dr Rob Williams, University of Bath; Professor Paul Verkade, Wolfson Imaging Center University of Bristol.
3. Determine how mutant ubiquitin (UBB+1) is regulated in Alzheimer’s Disease.
Lee Harris, ARUK-funded PhD student (2017-2021);
Collaboration with Dr Rob Williams, University of Bath; Professor Pat Kehoe and Professor Seth Love, South West Dementia Brain Bank.
2. Determine the function of novel ubiquitin-dependent molecular mechanisms in the cell cycle, and their relevance for brain cancer.
Natalie Vaughan Bath-University Research Studentship (2014-2018); Nico Scholz GW4 MRC BioMed studentship (2018-2022).
Collaboration with Dr Catherine Lindon, University of Cambridge; Dr Kathreena Kurian, Brain Tumour Research Group, Institute of Clinical Neuroscience, University of Bristol; Dr Florian Siebzehnrubl, ECSCI Cardiff University; Dr Mariann Bienz MRC-LMB Cambridge; Professor Benedikt Kessler, University of Oxford.