PhD Studentship: Allele-resolved genetics and epigenetics in type 2 diabetes

University of Exeter; Exeter; On-site; GBP 21,000 - 23,000; Full time

Benefits offered by this job

Stipend

Fees covered

EPSRC funded

Job summary

University of Exeter invites applications for a PhD studentship focusing on how genetic variants affect DNA regulation in pancreatic islets. The project uses Fiber-seq long-read sequencing to map regulatory activity and distinguish parental copies, advancing diabetes genetics.

You will join a multidisciplinary team with training in experimental design, sequencing, bioinformatics, and statistical genetics, receiving expert supervision and international collaboration opportunities.

Qualifications

• Experience in genetics/genomics research and data analysis.
• Strong computational and statistical skills with a biology background.
• Ability to work with large-scale sequencing data and collaborate.

Responsibilities

• Generate chromatin maps from healthy and diabetic islets using Fiber-seq.
• Analyze regulatory activity, epigenetic state, and genotype across parental copies.
• Integrate data with UK Biobank and other large cohorts for interpretation.
• Collaborate across lab and software teams with international partners.

Skills

Bioinformatics

Epigenetics

Chromatin sequencing

Education

Bachelor's degree in a related field

Tools

Oxford Nanopore

R/Python

Job description

Type 2 diabetes (T2D) affects over 800 million people worldwide. It is a complex disorder and an individual’s genetics influences disease risk. Understanding how DNA differences drive this risk can enable disease prediction and personalised approaches to diagnosis and treatment, addressing the shortfall between genetic discovery and patient benefit. Large scale genetic studies have identified hundreds of DNA regions linked to increased T2D risk. Most lie in regulatory regions, areas of DNA outside the genes that control when and where a gene is turned on. Changes here impact how islets – clusters of pancreatic cells that produce hormones including insulin – regulate blood glucose. Interpreting these DNA changes is complicated because we inherit two parental copies of our genome, and the disease-causing changes generally reside on only one. Standard technologies merge data from both copies, making it challenging to resolve which DNA changes contribute to disease.

This project will use chromatin stencilling (known as Fiber-seq), a cutting‑edge technology, to address this problem. This long‑read sequencing technology simultaneously measures regulatory activity, epigenetic state, and genotype and allows us to distinguish the two parental copies of the genome. Key question How do genetic variants associated with T2D alter regulatory activity on each inherited copy of our genome in pancreatic islets?

This will be achieved by:

1. Generating unprecedented chromatin stencilling maps of DNA regulatory activity from healthy pancreatic islet donors.
2. Targeting specific disease loci in islets from genetically selected type 2 diabetes donors to pinpoint failing regulation.
3. Decoding how genetic changes affect DNA regulation, enabling the interpretation of diabetes associated genetics in large studies like the UK Biobank. Interdisciplinary Approach This project brings together laboratory genetics, epigenetics, long‑read sequencing and extensive data science. The student will join the Gene Regulatory Defects in Disease Group at the University of Exeter, an interdisciplinary team of laboratory and computer scientists. The project will allow the student to shape the research direction, and they will receive expert supervision, training, andcollaboration with international leaders.

The student will develop translatable skills in experimental design, DNA sequencing, bioinformatics and interpreting complex biological data. Methodology Healthy and T2D islets will be selected using genetic, clinical, and existing molecular data. The islets will undergo our chromatin stencilling protocol,and the DNA will be sequenced using Oxford Nanopore. These long reads allow us to map activity to each inherited DNA copy and assess copy specific regulation. Targeted sequencing will also provide deep coverage at selected disease regions.

Computational analyses will then identify differences in DNA accessibility and methylation, resolving cell‑type specific regulation and annotating regulatory protein binding sites. This will be combined with large‑scale genetic (e.g. UK Biobank) to improve interpretation of variants in T2D. Outcomes This project will generate the most detailed maps to date of gene regulation in healthy and T2D pancreatic islets, improving our understanding of the genetic basis for T2D. The resulting openly shared annotations and datasets will be a resource for the community. Student training will also be a significant output, they will gain cross‑discipline expertise in long‑read sequencing, epigenetics, computational biology, and statistical genetics.

Funded by:EPSRC Engineering and Physical Sciences Research Council

£21,805. The studentship will provide funding of fees and a stipend of £21,805 per annum for 2026/7.