PhD Study : Crosstalk between muscle and pancreas: Role of irisin in pancreatic beta-cell function and blood glucose control

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Summary

Insulin is a major regulator of whole-body-metabolism, where crosstalk between pancreatic beta-cells and other insulin-responsive tissues plays a vial role in maintenance of glucose homeostasis and health. Type 2 diabetes mellitus (T2DM) is characterized by dysfunctional insulin-secretion coupled with reduced insulin-sensitivity, each of which have far-reaching consequences. While the breakdown in crosstalk between islets of Langerhans and insulin-responsive tissues is recognized, the involvement of other tissues in metabolic crosstalk is far-from-understood. Several mediators of crosstalk have been proposed including ghrelin (arising from stomach/pancreas), leptin (arising from fat), and osteocalcin (arising from bone), each playing a role in energy homeostasis.

The muscle-derived peptide, irisin, has recently been proposed to bridge exercise with metabolic homeostasis [Bostrom et al Nature 481: 463-468; 2012], representing a new exciting biomolecule that could play a major role in crosstalk between muscle and pancreas [see Chen et al Diabetes Metab Rev 32: 51-59; 2016]. Insulin-sensitive skeletal muscle is a major site for glucose utilization, glucose disposal/storage, and so represents an important therapeutic target in T2DM. Preliminary data suggesting that administration of irisin in vivo can influence insulin sensitivity, insulin secretion and glucose homeostasis [also see Duan et al Int J Biol Macromol 84: 457-463; 2016; Xin et al Int J Obes 40: 443-451; 2016], clearly prompts further in-depth studies to unravel the mechanisms underlying these promising effects.

The overarching aim of this proposal is to examine the effects of the myokine irisin on pancreatic-beta cell mass, viability, and function both in vitro and in vivo (coupled with measures of other metabolic factors/endpoints in both lean and obese diabetic rodents) using a range of methods established in our laboratory. In vitro investigations will examine actions of irisin in isolated rodent islets and established rodent and human beta-cell lines (INS-1, BRIN-BD11, and 1.1B4).

These studies will examine a range of actions including effects of irisin on insulin secretion alone and in the presence of  known physiological and pharmacological secretagogues, Other in vitro studies will determine the impact of exposure to irisin, in culture, on important beta-cell parameters such as proliferation/mass/function and protection/viability. In order to examine effects of irisin in vivo it will first be necessary to determine its stability and degradation profile in plasma, this will inform dosing regimens and assist the design of stable/long-acting forms of irisin that can effectively target beta-cells. The duration and comparative actions of native irisin and stable analogues will then be examined on a range of in vivo parameters, including circulating insulin and glucose, as well as pancreatic islet size/cellular composition and beta-cell mass in both lean and obese diabetic rodents. Importantly, the effects of irisin in the absence or presence of established antidiabetic drugs will be examined, both in vitro and in vivo, giving further insights into its potential utility in a therapeutic context for T2DM. This project, conducted within Ulster’s Diabetes Research Group, will provide excellent training in a broad range of techniques and result in high impact publications.

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
  • A comprehensive and articulate personal statement

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.

  • First Class Honours (1st) Degree
  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Research project completion within taught Masters degree or MRES
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Experience of presentation of research findings

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

The Doctoral College at Ulster University

Key dates

Submission deadline
Monday 19 February 2018
12:00AM

Interview Date
6, 7 and 8 March 2018

Preferred student start date
Mid September 2018

Applying

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