Studying rare genetic types of diabetes to identify genes essential for survival of insulin-producing cells

Investigating rare types of diabetes caused by specific genes to help improve treatments



We are hoping to find out which genes are crucial for the survival of cells that produce insulin. Disrupted endoplasmic reticulum (ER) stress leading to beta-cell death is a known contributor to type 2 diabetes. Understanding which genes are essential to regulate this cellular process and prevent beta-cell death could highlight new drug treatments to promote beta-cell survival in people with diabetes. 

What are we doing?

We hope our research will help to provide diagnoses for families with neonatal diabetes and also give insights into how more common forms of diabetes develop. 

We hope to do this by:

  • Identifying novel disease-causing genes essential for beta-cell survival in individuals with neonatal diabetes. 
  • Investigating whether heterozygous rare variants in essential ER stress genes contribute to adult-onset diabetes risk. 
  • Investigating the presence of recessive loss-of-function variants in ER stress genes in individuals without diabetes. 

How are we doing it?

We are studying genome sequencing data from neonatal diabetes patients with characteristics consistent with rapid beta-cell loss. We will use different approaches to identify genetic causes including prioritising candidate variants based on family structure and inheritance, identifying variants within the same genes across patients, and applying virtual panels of known ER stress genes. Genetic findings will be replicated by analysing the candidate gene(s) in the rest of the neonatal diabetes cohort and other disease relevant cohorts (e.g., 100,000 genomes project). We will also use resources such as the Exeter diabetes cohort and UK BioBank. 

BRC Colleagues

PhD Supervisor, Dr Elisa De Franco, University of Exeter

Professor Sarah Flanagan, University of Exeter

People involved

Dr Kashyap Patel

Project Researcher