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PhD Studentship: Investigating the Epigenetic Component of Insulin Secretion Disorders. MRC GW4 BioMed DTP PhD studentship 2024/25 Entry, PhD in Clinical and Biomedical Sciences

University of Exeter - HLS

Qualification Type: PhD
Location: Exeter
Funding for: UK Students
Funding amount: £18,662 per annum
Hours: Full Time
Placed On: 18th September 2023
Closes: 1st November 2023
Reference: 4867

The GW4 BioMed2 MRC DTP is offering up to 22 funded studentships across a range of biomedical disciplines, with a start date of October 2024.

These four-year studentships provide funding for fees and stipend at the rate set by the UK Research Councils, as well as other research training and support costs, and are available to UK and International students.

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 38 students over 2 cohorts in its second phase.

The 80 projects available for application, are aligned to the following themes;

Applications open on 4th September 2023 and close at 5.00pm on 1st November 2023.

Studentships will be 4 years full time. Part time study is also available.

Project Information

Research Theme:

Population Health Sciences

Summary:

During this PhD, you will use innovative bioinformatic techniques to investigate how epigenetic processes contribute to rare genetic disorders that affect insulin secretion. Critically, you will use these disease-specific epigenetic patterns to develop classifiers termed “episignatures” to assist with the interpretation of novel genetic variants and as a diagnosis tool.

Description:

Mendelian disorders, while individually rare, are collectively common affecting around 3.5% of the population. New sequencing technologies have revolutionised medical genetics and enabled the identification of rare mutations as the cause of many different disorders. However, determining the exact genetic cause can still be challenging when dealing with variants with unknown or uncertain clinical significance. Recently there has been increasing evidence that epigenetic modifications can assist in the interpretation of genetic variation.

Epigenetic modifications are biochemical modifications to DNA or DNA/protein complexes, which control gene expression independently of DNA sequence variation. Epigenetic processes such as DNA methylation are highly dynamic during development. Alterations in a developmental trajectory due to a change in the underlying genetic sequencing can therefore have profound effects on the epigenome. Thus, an altered DNA methylation signature can be propagated and maintained across multiple cell lineages resulting in a stable epigenetic signature of a monogenic disease.

The clinical laboratories in Exeter are a national and international referral centre for genetic testing for insulin secretion disorders; the Beta-cell Research Bank at Exeter provides a unique resource of >25,000 patient samples with DNA sequencing data available for thousands of these samples. Patients with congenital hyper- and hypoglycaemia represent the extreme ends of the spectrum in  terms of insulin secretion. Studying the underlying genetic aetiology of disease in these individuals provides a unique opportunity to improve understanding of pancreas development and function.

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