Starter Grant for Clinical Lecturers awardee 

Imperial College London

Studying the impact of biased GLP-1 receptor signalling in humans

To celebrate the 10 year anniversary of the Starter Grants for Clinical Lecturers scheme we are pleased to feature case studies of past and present Starter Grant awardees. Dr Ben Jones was awarded a Starter Grant for Clinical Lecturers in 2018. Here he explains what attracted him to the scheme and outlines his future research plans. He also highlights some of the main achievements of his research career so far.

Can you give us an overview of your research?

I am investigating a new approach, known as “biased signalling”, to target cell surface “receptors” in a very specific way to improve the therapeutic potential of drugs and reduce side effects. In comparison to existing drugs, the “biased” molecules I have developed selectively activate processes inside cells linked to beneficial effects and minimise those associated with adverse effects.

I am focussing in particular on the glucagon-like peptide-1 receptor (GLP-1R), an important receptor for control of blood sugar levels and appetite, for which a number of drugs are already available for treatment of diabetes. I have shown that introducing biased signalling into the GLP-1R system increases the blood-glucose lowering effect, whilst minimising nausea (the main side effect of this class of drugs).

What has the impact of your Starter Grant been so far?

My Starter Grant will support a human study testing the effects of biased GLP-1 receptor agonists in humans. This study, termed Receptor Trafficking in Incretin Action (“RETRO”), includes three separate parts to examine the effect of bias on different GLP-1R actions, namely appetite, post-prandial physiology, and pancreatic beta cell function.

The Starter Grant scheme was highlighted to me by senior colleagues soon after I was awarded my Clinical Lectureship. Previous Clinical Lecturers in my department have been recipients of this award and have gone on to achieve further substantial funding. The value of the award, when combined with the initial seed funding I obtained from the Imperial Biomedical Research Centre, will be ideal to allow me to complete the full study and perform comprehensive analyses.

What’s next for you and your research?

I plan to apply the paradigms developed for GLP-1R bias to other receptor systems. This will form the basis for a fellowship application (e.g. Wellcome Career Development Fellowship, stage 1; Diabetes UK Harry Keen Fellowship).

Research highlights

• Publication of previous work in Nature Commumications in 2018
• A number of successful funding applications in 2018 (Medical Research Council for £644,312; Engineering and Physical Sciences Research Council for £100,000; Society for Endocrinology for £10,000)