A Platform for the High-Throughput Screening of Reactive Fragments in Cells

University of Strathclyde

Establishing links between proteins and disease: Fluorescent binding of proteins lights the way to future therapies
Cells are complex organic machines that employ proteins to carry out their major functions. The proteins involved in cellular function are hugely varied, and defects or deficiencies in these proteins lead to the development of diseases. Establishing whether a protein is a suitable drug target requires the identification of inhibitors; small molecules that modulate the activity of a single protein. At present, inhibitors are only available for a small proportion of human proteins. ‘Reactive fragments’ represent an emerging class of molecules which interact with proteins, providing a starting point for the development of new inhibitors. It is preferable to screen reactive fragments against proteins of interest in live cells. However, the majority of existing methods examine the interaction of reactive fragments with isolated proteins and rely on mass spectrometry, which can only analyse one sample at a time.

James’s project seeks to develop a method to screen GSK’s full library of reactive fragments, over a thousand molecules, against proteins of interest faster than currently possible. The project will also investigate how traditional screening approaches can be adapted for testing in human cells, providing more biologically relevant results. Applying these newly developed techniques will enable analysis of thousands of protein-fragment binding events simultaneously, whereas current mass spectrometry-based analysis has to be completed one sample at a time. Over 85% of the human proteome, the full set of proteins present in the human body, lack chemical tools to analyse their function, this work will help fill those gaps and enable the study of these proteins and their role in disease. This research will help expedite the future drug discovery process, by accelerating the discovery of new medicines that can be tested in clinical trials.

James graduated in 2020 with a Master’s degree in Chemistry with Medicinal Chemistry from Imperial College London, where he made the Dean’s list in 2018. He has previously worked at Hurstpierpoint College teaching GCSE chemistry and mathematics and has undertaken an industrial placement at Sun Chemical to facilitate his chemistry experience.


“Having access to GSK’s bank of chemical resources and expertise is what makes this research possible. Bringing together vast industry data and academic knowhow will give that wealth of data purpose and hopefully speed the process of delivering new medicines to those who desperately need them.”