Contact: Dr. Andrew Thompson, Department of Medicine, and SMi Drug Discovery
Mentor: Peter Hill

The use of microscopy to observe biological processes has undergone huge advances in the last decade, an achievement recognised in 2017 with the Nobel Prize for Chemistry. A paralleled increase in commercial investment has coincided with the development of new fluorescent ligands which are revolutionising drug discovery.

Although membrane proteins make up only 25% of proteins, 50% of prescription drugs target them. In 2017, they represented 6 of the top 10 revenue generating drugs ($53 billion global sales). However, it is challenging to work with membrane proteins as they are often unstable when examined using traditional biochemical techniques. This means there is a large pool of potential therapeutic targets that has yet to be examined. Any method that aids the development of novel therapeutics targeting these membrane proteins would be seen as a turning point.

We have designed and constructed an automated, multi-colour, fluorescent microscope capable of viewing single-molecule interactions of drugs with membrane proteins in real-time. It is the first device to achieve such a high spatial (1.6 nm) and temporal (100 µs) resolution, and allows scientists to determine key components of drug-receptor interactions, such as the number, position, and rate constants of individual molecules. Using this technology it is now possible to directly observe an almost limitless diversity of molecular interactions across countless disease areas.

The challenge for the I-Team is to investigate the market potential for this new microscopy technique and identify the applications where it brings the greatest value.