PhD Study : Islet peptides and paracrine interactions in the physiological and dysfunctional regulation of islet hormone secretions

Apply and key information  

Summary

Islets of Langerhans are individual clusters of heterogenous cell types responsible for the secretion of insulin, glucagon and somatostatin plus an increasing number of unsuspected brain-gut peptides. Each cell type is regulated in a different manner by glucose, other nutrients and circulating factors. However, intra-islet autocrine or paracrine effects, whereby the secretory products of the islet cells affect secretory activity of surrounding cells, are likely to play an important role in both islet physiology and pathology in diabetes. For example, the well-known ability of glucagon-like peptide-1 (GLP-1) secreted by intestinal L-cells to inhibit glucagon secretion is not mediated by a direct action on alpha cells but via stimulation of somatostatin release from adjacent delta cells which in turn inhibits glucagon secretion. Such paracrine actions together with influence of autonomic nerves, nutrients and various circulating hormones normally interact to regulate insulin secretion and islet cell function, thereby ensuring tight control of glucose homeostasis. In addition to insulin, glucagon and somatostatin, we have recently demonstrated that the islet cells contain a surprising number of non-classical islet peptides.

This heterogeneity is not confined to but is particularly marked in alpha cells. These non-classical peptides include brain-gut hormones such as gastric inhibitory polypeptide (GIP), GLP-1, oxyntomodulin, GLP-2, peptide YY (PYY), cholecystokinin (CCK), gastrin, xenin, oxytocin and vasopressin.  These potentially important paracrine factors are co-localized with the classical islet peptides, possibly within distinct secretory granules, and when secreted may have a disproportionately large regulatory effect on insulin, glucagon or somatostatin secretion due to their high local concentration within the islet interstitial space and vasculature.

Core objectives of the proposed research are:

Determine the presence, precise chemical structure and cellular location of non-classical islet peptides in the pancreatic islets of normal and diabetic animals.

Examine the kinetics of their release from perfused pancreas in relation to the output of insulin, glucagon and somatostatin.

Evaluate the actions of natural physiological stimulators and drugs on islet cell secretions plus the effects of known peptide receptor inhibitors.

Dissect the involvement of islet cell interactions in the overall regulation of islet function in normal physiology and animal models of diabetes.

This project will involve techniques such as immunocytochemistry, tissue culture, cell incubations, small animal handling and experimentation, pancreas perfusion, islet isolation, PCR, gene silencing, fluorometric assay, radioimmunoassay, HPLC, MALDI-TOF and MSI. In addition, PCR and Western blotting will be utilised to explore gene and protein expression of key elements of signal transduction pathways plus cellular interactions between various islet cells (such as connexin 43, connexin 36, E-cadherin).

The proposed project will provide experience of cutting-edge research and afford comprehensive training in a wide range of in vitro and in vivo techniques. A background in biology, biomedical sciences, nutrition, pharmacology or related subject would be desirable.

Please note: Applications for more than one PhD studentships are welcome, however if you apply for more than one PhD project within Biomedical Sciences, your first application on the system will be deemed your first-choice preference and further applications will be ordered based on the sequential time of submission. If you are successfully shortlisted, you will be interviewed only on your first-choice application and ranked accordingly. Those ranked highest will be offered a PhD studentship. In the situation where you are ranked highly and your first-choice project is already allocated to someone who was ranked higher than you, you may be offered your 2nd or 3rd choice project depending on the availability of this project.

AccessNI clearance required

Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the project.

Essential criteria

Applicants should hold, or expect to obtain, a First or Upper Second Class Honours Degree in a subject relevant to the proposed area of study.

We may also consider applications from those who hold equivalent qualifications, for example, a Lower Second Class Honours Degree plus a Master’s Degree with Distinction.

In exceptional circumstances, the University may consider a portfolio of evidence from applicants who have appropriate professional experience which is equivalent to the learning outcomes of an Honours degree in lieu of academic qualifications.

  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • Clearly defined research proposal detailing background, research questions, aims and methodology

Desirable Criteria

If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.

  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Experience using research methods or other approaches relevant to the subject domain
  • Sound understanding of subject area as evidenced by a comprehensive research proposal
  • Work experience relevant to the proposed project
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Relevant professional qualification and/or a Degree in a Health or Health related area

Funding and eligibility

The University offers the following levels of support:

Vice Chancellors Research Studentship (VCRS)

The following scholarship options are available to applicants worldwide:

  • Full Award: (full-time tuition fees + £19,000 (tbc))
  • Part Award: (full-time tuition fees + £9,500)
  • Fees Only Award: (full-time tuition fees)

These scholarships will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance) and will provide a £900 per annum research training support grant (RTSG) to help support the PhD researcher.

Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Please note: you will automatically be entered into the competition for the Full Award, unless you state otherwise in your application.

Department for the Economy (DFE)

The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £19,000 (tbc) per annum for three years (subject to satisfactory academic performance).

This scholarship also comes with £900 per annum for three years as a research training support grant (RTSG) allocation to help support the PhD researcher.

  • Candidates with pre-settled or settled status under the EU Settlement Scheme, who also satisfy a three year residency requirement in the UK prior to the start of the course for which a Studentship is held MAY receive a Studentship covering fees and maintenance.
  • Republic of Ireland (ROI) nationals who satisfy three years’ residency in the UK prior to the start of the course MAY receive a Studentship covering fees and maintenance (ROI nationals don’t need to have pre-settled or settled status under the EU Settlement Scheme to qualify).
  • Other non-ROI EU applicants are ‘International’ are not eligible for this source of funding.
  • Applicants who already hold a doctoral degree or who have been registered on a programme of research leading to the award of a doctoral degree on a full-time basis for more than one year (or part-time equivalent) are NOT eligible to apply for an award.

Due consideration should be given to financing your studies. Further information on cost of living

Recommended reading

​Dawood Khan, Charlotte Moffett, Peter R. Flatt and Catriona Kelly (2018). Role of islet peptides in beta cell regulation and type 2 diabetes therapy. Peptides,100, 212–218.

Catriona Kelly, Neville H. McClenaghan and Peter R. Flatt (2011). Role of islet structure and cellular interactions in the control of insulin secretion. Islets, 3, 41-47. ​

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 28 February 2022
12:00AM

Interview Date
April 2022

Preferred student start date
mid September 2022

Applying

Apply Online  

Contact supervisor

Dr Yasser Abdel-Wahab

Other supervisors