Combining multiple bullets against a sweet target - Fragment-based drug discovery to tackle cancer glycosylation

Funded by the CDT in Chemical Biology: Innovation in Life Sciences – 1+3 year PhD studentships

This studentship in the ICB CDT is co-funded with GSK.

Supervisors: Dr Benjamin Schumann | Dr David House | Professor Ed Tate

Glycosylation is a ubiquitous posttranslational protein modification, and highly glycosylated proteins are overexpressed as a hallmark of metastatic cancer. The addiction of cancer cells to structural alterations of glycans makes the process of glycosylation an important yet underexplored target for therapeutic intervention. This project, co-funded by GlaxoSmithKline, will focus on fragment-based drug discovery to generate glycosylation enzyme inhibitors. We will combine newly-available chemical space and modelling approaches to generate lead compounds with suitable interaction profiles. Biological evaluation will be performed to develop a drug that hits glycosylation, the sweet tooth of cancer.

This multidisciplinary project will be performed at the Francis Crick Institute (London), one of the world’s leading biomedical research institutes. Embedded in this exceptional environment that includes access to the Crick Science Technology Platforms, the student will be a part of the Chemical Glycobiology Group and establish close ties with the GSK LinkLabs at the Crick. The student will be trained in methods of protein expression and crystallography, modelling, enzyme assays and lead development as well as in-depth biological evaluation. A research placement at GSK’s R&D site in Stevenage will expose the student to cutting-edge drug discovery infrastructure. We are looking for an outstanding student with a chemistry, chemical biology or related background and exposure to biological research, ideally in the context of drug discovery. Theoretical knowledge in any facet of drug discovery and glycobiology is highly desirable.