PhD Study : Actions and mechanisms underlying complementary therapeutic actions of GLP-1 and NPY receptor modulation for diabetes

Summary

The obesity and type 2 diabetes epidemic are becoming so advanced that almost every country will struggle with the major financial and healthcare implications. Accordingly, new approaches to curtail obesity and related diabetes are of considerable therapeutic interest. In this regard, regulatory hormones derived from either the pancreas or the gastrointestinal tract (GIT) have long been recognised as a source of new drug targets for obesity-diabetes. This is highlighted by the recent successful clinical application of glucagon-like peptide-1 (GLP-1) mimetics for both obesity and diabetes. In addition, recent FDA approval of a hybrid peptide with dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor modulating actions for diabetes, demonstrates antidiabetic efficacy of peptide therapies beyond GLP-1. As such, neuropeptide Y receptors (NPYR), activated by members of the NPY peptide family including Peptide YY (PYY) and Pancreatic Polypeptide (PP), can induce weight loss and/or improve pancreatic islet function.

At Ulster, we have developed patent protected PYY and PP molecules that exert direct benefits on pancreatic beta-cell function and promote reductions in energy intake. Moreover, we have published and unpublished data to demonstrate clear antidiabetic efficacy of these PYY and PP compounds both alone, and in combination with GLP-1 mimetics.

Utilising this new knowledge, the following research objectives will be addressed as part of this PhD project

These include:

*Assess the in vitro enzymatic stability of novel PP and PYY peptides

*Consider design of enzymatically stable dual-acting GLP-1 and NPY receptor hybrid peptides

*Examine biological actions of novel PYY and PP peptides in BRIN BD11 cells and perfused isolated mouse islets

*Establish in vivo satiety effects as well as glucose-regulatory and insulin secretory actions of all test peptides

*Assess the beneficial effects of combined GLP-1 and NPY receptor activation in rodent models with different aetiologies of diabetes

Please note: Applications for more than one PhD studentship 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.

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
• 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