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Understanding the mechanism of insulin secretion from islets

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  • Full or part time
    Prof R Duncan
    Dr Colin Rickman
    Dr S Forbes
  • Application Deadline
    No more applications being accepted
  • Funded PhD Project (European/UK Students Only)
    Funded PhD Project (European/UK Students Only)

Project Description

Medical Research Scotland
PhD Studentship Award

This project is one of 15 four year PhD Studentships funded by Medical Research Scotland (http://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and Company. The Studentship will provide the first-class academic and commercial training needed to equip the successful candidate for a science career in an increasingly competitive market.

"Why is human insulin secretion temporally disrupted in diabetes?" to be delivered by Heriot-Watt University [Supervisors: Dr Rory Duncan, Dr Colin Rickman (both Institute of Biological Chemistry, Biophysics & Bioengineering, Heriot-Watt University) and Dr Shareen Forbes (Centre for Cardiovascular Science, University of Edinburgh] and Miltenyi Biotec Ltd (www.miltenyibiotec.com) [Company supervisor: Dr Sebastian Knobel].

The mechanism of insulin secretion from islets is incompletely understood, and specific defects in relation to Type 2 diabetes and following islet transplantation remain to be elucidated. Islets secrete insulin in two phases. The first phase of insulin secretion represents release of insulin from pre-formed insulin granules, classically measured in the first 10 minutes following intravenous glucose stimulation and the second phase represents insulin that is manufactured de novo following this time. Defects in first phase insulin secretion are seen in Type 2 diabetes and represents one of the earliest features of the condition. Patients with Type 1 diabetes cannot secrete insulin and are reliant on insulin injections. Islet transplantation, where islets are placed into the liver of a recipient with Type 1 diabetes, may stabilise glucose control and may be life-saving; the patient, however, needs to take immunosuppression or anti-rejection drugs, in order to not reject the transplanted islets. In subjects that have undergone islet transplantation, first phase insulin secretion has also been shown to be consistently blunted. The underlying pathophysiological mechanism underling this defect have not been explored and previous imaging techniques have lacked resolution to track this process.

In this project we will aim to examine insulin secretion using state of the art super-resolution imaging and spectroscopic techniques. In combination with approaches we have developed previously (Nature. 2003 Mar 13;422(6928):176-80), we will examine insulin secretion in isolated rodent islets making use of transgenic rodent models that constitutively express fluorescent proteins on membrane structures, alongside metabolic assessments of such islets and aim to unravel the key steps that lead to defective first phase insulin secretion. Islets will be examined with and without immunosuppressive agents to determine if there are particular problems with insulin secretion secondary to these agents. The function of transplanted islets will also be examined in vivo in rodent models, based on the results of our in vitro studies. In subsequent experiments, the function of human islets will be examined, making use of human islets isolated locally in the Scottish Islet Transplant Programme.

ENQUIRIES:
Enquiries should be sent by email to Dr Rory Duncan:
[email protected]

APPLICATIONS:
The position would suit an enthusiastic student who must have obtained a first or 2.1 UK BSc Honours degree, or equivalent for degrees obtained outside the UK, in molecular biology or a related discipline.

Applicants should send a CV, the contact details of 2 references (including email addresses) and a covering letter, explaining why the applicant wishes to carry out this project, by email to Mrs Maureen Franks:
[email protected]

Interviews are expected to take place in mid-April 2017.

It is anticipated that the PhD Studentship will start between July and September 2017, or as soon as possible thereafter.

Funding Notes

PhD Studentship provides: an annual tax-free stipend of £17,500, increasing to £18,000 over the four years; tuition fees at UK/EU rates only; consumables; and contribution to travel expenses. International fees are not covered.

References

Professor Rory Duncan - www.esric.org
Dr Shareen Forbes - http://www.cvs.ed.ac.uk/profiles/shareen-forbes/60c90817-bb6a-4571-adf7-3f6f9f6c476a (website in process of being updated)

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