PhD Study : Novel fatty acid receptors in islet cells as therapeutic targets for diabetes

Apply and key information  

Summary

The prevalence of type 2 diabetes has risen dramatically during recent decades and there is an urgent need to develop new approaches for disease treatment. In recent years, therapies that target the actions of glucagon-like peptide-1 (GLP-1) which stimulate insulin secretion through activation of beta cell G-protein coupled receptors (GPCRs) have been successful. This has resulted in substantial interest in targeting other islet GPCRs for diabetic therapies [1-3]. There is an increasing need for new pharmaceutical therapies which preserve beta cell function, decrease weight gain and represent a low risk of hypoglycaemia in diabetes treatment. GPCRs have become the target of approximately 50% of recently developed pharmaceutical agents. Our published work demonstrates that GPCRs activated by endogenous and synthetic agonists in islets, are co-localised with insulin on islet beta cells, and exhibit insulinotropic and glucose lowering activity [4-9].

This research project represents an important step in the validation of these islet targets for improved diabetes treatment and care. The multi-faceted research expertise and vision of the Diabetes Research Group coupled with a highly productive team of internationally recognized scientists offers a strong foundation for studentship training.

This studentship will investigate the biological activation of novel GPCRs as therapeutic targets for type 2 diabetes treatment and aims to:

(i)Determine the regulatory role of novel GPCRs on pancreatic function and explore intracellular signalling events activated by GPCRs.

(ii)Investigate GPCR gene knockout using CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats) gene editing and analyse the role of GPCRs in intestinal cell physiology and hormone secretion.

(iii)Determine the metabolic and beneficial effects of GPCR agonist therapies in type 2 diabetes and related disorders in vivo.

The worldwide increase in the incidence of obesity, metabolic syndrome and type 2 diabetes demands the development of new drugs for safe and effective treatment, limiting the progression to long-term diabetic complications. Targeting G-protein coupled receptors (GPCRs) may be used to counteract defective insulin secretion, low beta cell mass and insulin resistance associated with type 2 diabetes and related disorders.

References:

1.Moran BM, Flatt PR, McKillop AM. (2016) Acta Diabetol. 53(2):177-88.

2.Moran BM, McKillop AM, O'Harte FPM. (2016). Curr Opin Pharmacol. 31:57-62.

3.Ahren B. (2009). Nature Reviews 8: 369-385.

4.McCloskey AG, Miskelly MG, Flatt PR, McKillop AM. Eur J Pharm Sci. 142: 105104 doi: 10.1016/j.ejps.2019.105104. [Epub ahead of print].

5.McKillop AM, Moran BM, Abdel-Wahab YH, Flatt PR. (2013). Br J Pharmacol 170(5):978-90.

6.McKillop AM, Moran BM, Abdel-Wahab YH, Gormley NM, Flatt PR. (2016) Diabetologia 59(12):2674-2685.

7.Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM. (2014). Biological Chemistry 395:453-64.

8.Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM. (2014). Diabetes Obes Metab. 16:1128-39. 9.Moran BM, Abdel-Wahab YH, Vasu S, Flatt PR, McKillop AM. (2016) Acta Diabetol 53(2):279-93.

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

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
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • Use of personal initiative as evidenced by record of work above that normally expected at career stage.
  • 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

The Doctoral College at Ulster University

Key dates

Submission deadline
Friday 7 February 2020
12:00AM

Interview Date
9 to 20 March 2020

Preferred student start date
Mid September 2020

Applying

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Contact supervisor

Professor Aine McKillop

Other supervisors