- Sponsored PhD student will join Professor Ed Tate’s group at Imperial, in the EPSRC Centre for Doctoral Training in Chemical Biology
- Project aims to develop the next generation of small molecule ABPs that will enable DUB activity in intact cells and organisms to be comprehensively explored and interrogated
The student will undertake a research project entitled ‘Unlocking DUB probe discovery by high-throughput in-cell chemical proteomics’. Building on Ubiquigent’s DUB-focused drug discovery platform and recent advances in activity-based probes (ABPs) at Imperial, the four-year project aims to create a new generation of small molecule APBs that will enable DUB activity in intact cells and organisms to be comprehensively explored and interrogated.
The project is sponsored by Ubiquigent and the EPSRC CDT, and the student will be mentored by Drs Sheelagh Frame (CEO), Rishi Shah (Head of Chemistry) and Joao Oliveira (Principal Scientist) at Ubiquigent, as well as Professor Ed Tate and Drs Fangyuan Cao and Jack Houghton at Imperial. The project will also benefit from the state-of-the-art facilities available at the £200 million Molecular Sciences Research Hub at the new Imperial White City Campus in London, and the extensive science ecosystem of the Institute of Chemical Biology CDT, which is among the world’s largest centres for integrated multidisciplinary training in chemical biology.
With the dysregulation of DUB activity implicated in a number of human diseases, DUBs present promising drug targets. However, although several DUB inhibitors are already in preclinical or clinical development, target validation has proven challenging, and there remains an urgent need for novel ABPs that can overcome the limitations of current ubiquitin-based probes which cannot be used directly in intact cells or organisms. Developing a new high-throughput chemical proteomic technology platform to overcome this barrier, the project will also enable Ubiquigent to further advance its target engagement assays for DUB-focused drug discovery and development, such as DUBprofiler-Cell™, DUBprofiler-Tissue™, and DUBatlas™.
Dr Rishi Shah, Head of Chemistry at Ubiquigent, said: “We are thrilled to support the PhD student, Jiaying Zhuang, within Professor Ed Tate’s group at Imperial College London, facilitating a collaboration with a world-renowned group in the field of chemical probes and protein modification. The opportunity to discover novel DUB ligands and further advance the possibilities of controlling protein homeostasis through DUBTAC development in a variety of therapeutic areas is particularly exciting.”
Professor Ed Tate, GSK Chair in Chemical Biology, Department of Chemistry at Imperial College London, added: “We are excited to be working with Ubiquigent on this project, leveraging the company’s industry-leading discovery and screening capabilities to develop a new chemical proteomic platform to explore DUB activity in cells. By delivering the first in-cell screens of large compound libraries we aim to identify novel and selective DUB probes and inhibitors, revealing starting points for new classes of medicines.”
