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Funded PhD Opportunity

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

Subject: Biomedical Sciences


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. Approaches to counteract defective insulin secretion and low beta cell mass in diabetes are key in developing therapeutic strategies. 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 [4-8]. This research project represents an important step in the validation of these islet targets for improved diabetes treatment and care. This studentship will investigate the biological activation of two GPCRs as therapeutic targets for type 2 diabetes treatment. 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 research project provides an excellent research training opportunity and represents an important step in the validation of GPCR targets for improved diabetes treatment. The specific project aims:

(i)To determine the functional role of novel GPCRs in the regulation of insulin and glucagon secretion using the clonal pancreatic beta cell line and alpha glucagon secreting cell line; (Milestones: 0-6 months)

(ii)To investigate the mechanism of action and intracellular signalling events activated by islet GPCRs and determine their role in the regulation of cellular proliferation and islet cell mass; (Milestones: 0-12 months)

(iii)To explore the response to activation of GPCR receptors expressed in intestinal cells using GLUTag (GLP-1 secreting) cell line, pGIPneo STC-1 (GIP secreting) cell line, and primary intestinal tissues; (Milestones: 12-24 months)

(iv)To investigate gene knockout of GPCRs in BRIN-BD11 cells using CRISPR/Cas9 (Clustered regularly interspaced short palindromic repeats) gene editing tool; (Milestones 14-24 months)

(v)To determine the effects of GPCR agonist monotherapy and combination therapies with other established diabetic therapies such as dipeptidyl-peptidase-IV (DPP-IV) inhibitors in vivo (Milestones 24-36 months).

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

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

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

7.Moran BM, Abdel-Wahab YH, Flatt PR, McKillop AM. (2014). Diabetes Obes Metab. 16:1128-39.

8.Moran BM, Abdel-Wahab YH, Vasu S, Flatt PR, McKillop AM. (2016) Acta Diabetol 53(2):279-93.


Essential criteria

  • Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC)
  • 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

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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 studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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 studentship grant (RTSG) allocation to help support the PhD researcher.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees for three years (subject to satisfactory academic performance). This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 15,009 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. This scholarship also comes with £900 per annum for three years as a research training studentship grant (RTSG) allocation to help support the PhD researcher.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies


Other information


The Doctoral College at Ulster University


Reviews

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

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Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

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Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Key dates

Submission deadline
Monday 19 February 2018

Interview Date
6, 7 and 8 March 2018


Applying

Apply Online  


Contact supervisor

Professor Aine McKillop


Other supervisors

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