Drug Discovery in a Mass Spectrometer

Project ID: 2531bc1603

(You will need this ID for your application)

Research Theme: Physical Sciences

Research Area(s): Chemistry

UCL Lead department: School of Pharmacy

Department Website

Lead Supervisor: Matthew Todd

Partner Organisation: AstraZeneca UK Limited

Stipend enhancement: £ 2,500

Project Summary:

Finding new medicines relies, as the first step, on finding small molecule binders of important proteins. We have developed powerful ways to do that using mass spectrometry, revealing commercially-available small molecules that bind target proteins.

But the molecules need optimising – they need to be potent, selective and they need to work inside a cell.

Traditionally, this optimisation is done bit by bit using medicinal chemistry, in cycles of making and measuring.

What if we could again use mass spectrometry (which is fast and sensitive) to detect better binders, but now not from a library but from crude mixtures of molecules we have made ourselves? What if, in other words, we could do medicinal chemistry in a mass spectrometer?

This would speed up the process of drug discovery enormously, allowing us to kick-start campaigns against all sorts of proteins central to human disease.

In this project we aim to generate this proof of concept – accelerating drug discovery with mass spectrometry. You will be working with two groups with expertise in these techniques, one at UCL in central London and one at AstraZeneca in Cambridge; the project is mostly at UCL with placements at AZ. You will be doing organic synthesis, mass spectrometry and you will have the chance to evaluate small molecule-protein binding with biophysical methods (like SPR) and X-ray crystallography, if you would like. The proteins we use will be generated by other group members and collaborators across the Structural Genomics Consortium of which the UCL PI is a member.

We are looking for a creative, hard-working experimentalist with a high level of initiative, interested in working as part of a team across academia and industry.