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Neural control of pancreatic islet function - PhD in Medical Studies (Research England DTP) Ref: 3873

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  • Full or part time
    Prof L Briant
    Prof C Yang
    Dr C Beall
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description



Due to a major recent award, applications are invited from students wishing to further their scientific careers by undertaking a PhD in a diabetes related area of research. Up to five studentships will be fully funded from autumn 2020 with enhanced stipends funded from a new £6million award. This award reflects Exeter as a world renowned centre of excellence for diabetes research.

Students can select from any of the advertised five projects. These projects have been carefully selected to provide students with an excellent scientific training in an important area of diabetes research, the latest laboratory and computing skills, outstanding resources, and with world leading scientists as supervisors. They cover various aspects of diabetes research, including autoimmunity in the pancreas; neuro-endocrinology to understand the relationship between the brain, mental health and the endocrine system; gene regulation in the placenta and fetal development of the pancreas; rare genetic forms of diabetes; muscle physiology; and the use of electronic medical records to understand disease causes, treatments and progression. Students will learn a wide range of state-of-the-art techniques, which could include CRISPR-Cas9 gene editing, DNA methylation, DNA sequence analysis, muscle insulin sensitivity physiology, brain electrophysiology, medical statistics, R for statistics and data visualisation and programming in python, data science including machine learning, in vivo metabolic phenotype skills and cell biology including 3D stem cell culture. Students will have access to outstanding resources, including cohorts of >5000 patients with rare defects in insulin secretion, a world leading collection of samples for study of pancreas pathology, resources of electronic medical records and biobanks from millions of people and unique resources for studying human development of the pancreas and brain.

Funding Notes

This is a 3 year fully-funded PhD studentship. Stipends are at an enhanced rate of £17,059 (2020-21) and all Home/EU tuition fees are covered. Funds will also be available for travel and research costs.

Project Description

Treating diabetes costs the NHS £1.5million/hour! The pancreatic beta-cells secrete insulin, and these cells become dysfunctional in diabetes. It is therefore critical that we understand how beta-cell function is regulated. In this project the student will develop transgenenic models and electrophysiology and imaging techniques to understand how the brain regulates beta-cell function.

In this project the student will have the opportunity to work at the interface of neuroscience and beta-cell biology. The project outline is as follows:

Year 1: Islets consist of 3 main hormone-releasing cell types: insulin-releasing beta-cells, glucagon-releasing alpha-cells and somatostatin-releasing delta-cells. All of these cells are electrically active, and they utilise these electrical signals to drive hormone secretion (Rorsman & Ashcroft, 2018, Briant et al., 2018). Therefore, to understand the regulation of beta-cell function, we must use (patch-clamp) electrophysiology to interrogate the electrical properties of beta-cells. The student will begin by learning the basics of electrophysiology as well as the microdissection of islets, animal husbandry, Crispr-Cas9 mutagenesis and the generation of transgenic tools in zebrafish (ZF). ZF have pancreatic islets and are highly amenable to studying islet function with different transgenic tools due to their high reproductive rate, rapid development, and optical transparency. We have conducted significant work on this model (Yang et al., 2018) and plan to map out brain regions that regulate ZF islet function.

Year 2: The student will develop techniques for studying the regulation of ZF islet function in vivo by combining optogenetics with confocal microscopy. This will allow a systematic characterisation of the brain regions involved in regulating islet function. Identified neurotransmitters will be explored in mouse and human islets. The student will present his/her results at international conferences.

Year 3: The student will study what happens to islet function when identified brain regions have been chemically/genetically ablated.

Resources:
Confocal microscope
Significant funding from host labs
Electrophysiology set-up
Access to animal facility and all associated equipment
Access to all software/guidance for analysing data

Skills learnt:
- electrophysiology and imaging
- primary mouse/human islet cultures
- Crispr-Cas9 mutagenesis
- generation of transgenic/knock-in reporter/optogenetic tools
- molecular biology
- analysis of data
- presenting, writing

Funding Notes

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree. Applicants with a minimum of Upper Second Class degree and significant relevant non-academic experience are encouraged to apply.

Applicants must ensure that they meet the eligibility requirements of the University of Exeter. To qualify for ‘home’ tuition fee status, you must be a UK or EU citizen who has been resident for 3 years prior to commencement.

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