Development of novel therapies for type 2 diabetes

About the Project

A PhD studentship is available between the groups of Dr Chris Coxon and Dr Lizzie Haythorne at the University of Edinburgh; School of Chemistry and the British Heart Foundation (BHF) Centre of Research Excellence.

https://www.edinburghmetabolism.co.uk/elizabeth-haythorne

https://edwebprofiles.ed.ac.uk/profile/dr-christopher-r-coxon

Background:

Type 2 diabetes (T2D) is a global health problem characterised by chronic hyperglycaemia due to inadequate insulin secretion from the pancreatic β-cell [1]. Disruption of glucose homeostasis not only underpins T2D development, but also significantly elevates the risk of cardiovascular disease. Current therapies (i.e. sulphonylureas, GLP-1 receptor agonists, insulin, metformin) treat the complications of T2D but none of these approaches provide any long-term benefit regarding β-cell health and insulin secretion. Because glucose must be metabolised to stimulate insulin release, drugs that stimulate glucokinase (GK) (the first enzyme in glucose metabolism) have been shown to enhance insulin secretion in diabetes. However, in the long-term, GK activators have been largely disappointing [2]. Recent studies show that hyperactivation of glucose metabolism underlies the progressive decline in β-cell function in diabetes [3]. Therefore, GK activators may exacerbate this decline (by promoting excessive glucose metabolism) and, counterintuitively, GK inhibitors should be a better therapeutic strategy for preserving β-cell function in T2D.

Aim:

This PhD project aims to investigate whether partial inhibition of GK can preserve β-cell function during metabolic stress, and to develop synthetic peptides which inhibit GK as a potential therapy for treating T2D.

Training and skill development

The student will receive training in a number of highly-interdisciplinary skills as follows: in vitro cell culture techniques (rodent and human cell lines and pancreatic islets from cadaveric donors), in vivo physiology (glucose and insulin tolerance tests), hormone secretion assays, biochemical enzyme activity assays, measurements of cellular metabolism (extracellular flux assays, real-time fluorescence microscopy, metabolomics), measurement of cellular stress (e.g. oxidative, ER), qPCR, western blotting computation, and peptide design, selection, synthesis and testing in biochemical kinase assays.

The student will benefit from world-leading research facilities and the vibrant research communities in both The School of Chemistry and The Queens Medical Research Institute. This is an excellent opportunity for a candidate with a chemistry or biology background with an interest in diabetes/cardiometabolic disease and who wants to gain interdisciplinary skills.

Applying

The expected start date is September 2026. Informal enquires are encouraged via email to Dr Chris Coxon (Chris.Coxon@ed.ac.uk) or Dr Lizzie Haythorne (ehaythor@ed.ac.uk).

In the first instance, the initial application of cover letter and CV should be directed to:

Dr Chris Coxon (Chris.Coxon@ed.ac.uk).

Closing date: open until suitable candidate is appointed.

The University reserves the right, in its sole discretion, to amend or withdraw any of the advertised scholarships, without further notice.

IMPORTANT

Before Submitting your cover letter and CV, please complete the online School of Chemistry Equality, Diversity & Inclusion Form for 26/27 Entryhttps://eur02.safelinks.protection.outlook.com/?url=https%3A%2F%2Fapp.onlinesurveys.jisc.ac.uk%2Fs%2Fedinburgh%2Fschool-of-chemistry-equality-diversity-inclusion-form-2024&data=05%7C02%7C%7C344514367973491046e608de0247791b%7C2e9f06b016694589878910a06934dc61%7C0%7C0%7C638950703149978905%7CUnknown%7CTWFpbGZsb3d8eyJFbXB0eU1hcGkiOnRydWUsIlYiOiIwLjAuMDAwMCIsIlAiOiJXaW4zMiIsIkFOIjoiTWFpbCIsIldUIjoyfQ%3D%3D%7C0%7C%7C%7C&sdata=ybdmRpTrGLQbjUSfKXwD7ERuoPGaKJgiBM46hI8EGKw%3D&reserved=0

The form will automatically generate a unique ‘Receipt Number’ that you must include in your cover letter.

Funding Notes

The studentship is fully funded for 42 months by the University of Edinburgh and covers tuition fees and an annual stipend at the UKRI rate, for 2026-27 this is £21,805 per annum, for a candidate satisfying EPSRC residency criteria. View Website

Funding comes jointly from the University of Edinburgh’s BHF Centre of Research Excellence and School of Chemistry, as part of an initiative to promote interdisciplinary research between biomedical disciplines and the physical sciences.

References

1. U.K. Prospective Diabetes Study 16. (1995). 44, 1249-1258.
2. Ashcroft, FM. et al. (2023) Trends Endocrinol Metab. 34:119-130.
3. Haythorne, E. et al. (2022) Nat Commun. 13, 6754.
4. Raimondo, A. et al. (2015). Curr Opin Lipidol. 26:88-95.