Genetic tools to probe E3 ligase-substrate interactions

Key Facts

Speaker: Dr. Richard Timms
Employer and Department:
Cambridge Institute of Therapeutic Immunology & Infectious Disease
Date and Time:
Thu 09th May 2024 - 12:00

Joint MRC Protein Phosphorylation and Ubiquitylation and CeTPD Seminar



How does the ubiquitin-proteasome system achieve selective protein degradation? The primary specificity determinants are considered to be the E3 ubiquitin ligases, which recognise cognate ‘degron’ motifs found in substrate proteins. However, for the majority of the >600 E3 ligases encoded in the human genome we still have little or no knowledge as to their substrates, and our understanding of degron motifs remains very limited. We seek to exploit the sophisticated genetic tools that are now available for the manipulation of human cells to identify the substrates and degrons recognised by E3 ligases, with the goal of illuminating novel regulatory pathways governing critical cellular processes


Richard recently started his independent laboratory at the Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID). The goal of his work is to develop and exploit genetic tools to understand how the ubiquitin-proteasome system achieves selective protein degradation. Richard’s interest in genetics began as a PhD student with Prof. Paul Lehner at the Cambridge Institute of Medical Research, where he developed genetic screens in haploid human cells to study viral E3 ubiquitin ligases. Then, as a Sir Henry Wellcome Postdoctoral Fellow working in the lab of Prof. Steve Elledge at Harvard Medical School, he discovered a range of novel degradative pathways through which Cullin-RING E3 ligases target degrons located at the extreme N- and C-termini of their substrates. The expression screening techniques that he developed to interrogate E3 ligase-substrate interactions form the basis of work in his new lab.