PhD Studentship: Uncovering new genetic mechanisms of beta-cell autoimmunity to better understand type 1 diabetes. MRC GW4 BioMed DTP PhD studentship 2025/26 Entry, Department of Clinical and Biomedical Sciences

Project description

About the GW4 BioMed2 Doctoral Training Partnership 

The partnership brings together the Universities of Bath, Bristol, Cardiff (lead) and Exeter to develop the next generation of biomedical researchers. Students will have access to the combined research strengths, training expertise and resources of the four research-intensive universities, with opportunities to participate in interdisciplinary and 'team science'. The DTP already has over 90 studentships over 6 cohorts in its first phase, along with 58 students over 3 cohorts in its second phase. 

Project Information 

Research Theme: Infection, Immunity, Antimicrobial Resistance & Repair

Summary:

This project uses a unique collection of samples from people with diabetes to address a fundamental question: What are the genetic mechanisms underpinning beta-cell autoimmunity?

Over a century since the discovery of insulin, and four decades since the recognition that type 1 diabetes (T1D) is an autoimmune disease, the mechanisms underlying T1D remain unsolved.

By identifying new genetic forms of autoimmune diabetes, you will develop a powerful combination of skills in genomics, immunology, and clinical research, providing new diagnoses to these families and uncover new mechanisms of beta-cell destruction - the first step towards the ultimate goal of preventing T1D.

Main Description:

The mechanisms that lead to autoimmune beta-cell destruction in T1D remain poorly understood. It is known that there are different routes that lead to autoimmune beta-cell destruction, and increasingly it is recognised that treatment to prevent this ‘friendly-fire’ may have to be tailored an individuals’ specific form of autoimmunity.

When diabetes presents as part of a syndrome of autoimmunity it is often caused by a single genetic variant. This is termed monogenic autoimmune diabetes, which generally presents early in childhood with complex disease that is difficult to manage clinically. Identifying and diagnosing monogenic autoimmunity can allow for tailored treatments for individual patients, improving clinical outcomes.

The genetic changes resulting in monogenic autoimmune diabetes impact a specific pathway that results in a loss of immune regulation leading to beta cell autoimmunity. These unique individuals living with rare monogenic conditions offer a window to understanding the diverse mechanisms that underlie more common forms of autoimmunity such as type 1 diabetes. Thus, these identified mechanisms may be exploited in developing therapies to prevent type 1 diabetes.

To date, the Exeter team have published 4 novel genetic causes of monogenic autoimmune diabetes, with a further 3 unpublished genes identified awaiting functional characterisation. The student will build on this work to study the mechanism(s) behind how these and newly identified gene variants contribute to beta-cell autoimmunity.

Key research question & project aims:

This project involves studying a unique collection of patient samples to answer a key outstanding question; What are the genetic mechanisms that underpin beta-cell autoimmunity?

The specific objectives of this project are to;

1. Identify families for gene discovery from an existing cohort
2. Robust analysis of whole genome sequencing data to identify new candidate genes
3. Replicate novel genetic findings in the wider Exeter cohort (>1000 individuals)
4. Characterise genetic variants through analysis of clinical data and functional immune studies

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