PhD Study : Engineering of stable neuromedin-U (NMU) octapeptide analogues and related dual-agonist peptides for use in diabetes and obesity therapy

Summary

Gut cells produce natural peptide hormones that are released into the bloodstream after a meal. These include key incretin hormones (GLP-1 and GIP), which help to regulate blood glucose through promoting release of pancreatic insulin. This incretin approach has proved clinically effective over for the past two decades in managing Type 2 diabetes and more recently obesity.  The current success of this strategy has emerged as a result of progressive innovation from the laboratory setting towards human clinical trials. Recent release of a new drug tirzepatide, targets both GLP-1 and GIP incretin actions simultaneously. This dual targeting approach has enabled the realisation of an exciting new peptide drug therapy which has thus far has proven highly effective for combatting the metabolic abnormalities found in both Type 2 diabetes and obesity.

Here we hope to exploit the expected metabolic benefits of another gut peptide family, which contains the peptide neuromedin U (NMU-25). Thus we will examine the actions of the shortened form of neuromedin-U (NMU-8) and related stable forms thereof, upon insulin secretion from pancreatic beta-cells, as well as on satiety and reduction of food intake in mice. If these actions as predicted, prove beneficial, then the NMU-8 will be incorporated into a dual-agonist peptide that could be highly effective for the treatment of both Type 2 diabetes and obesity. Therefore, the ultimate aim of the present project is to combine NMU-8 actions with the above mentioned GLP-1 incretin approach into a single dual acting peptide entity. These so-called ‘dual agonists’ should promote simultaneous activation of separate receptor pathways, which can be exploited in development of a unique class of peptide drugs. This pre-clinical development work could prove crucial in bringing forward a new class of dual agonist drug and subsequently help spur on their exciting clinical development by Pharma.

Important Information: 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
• 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
• Practice-based research experience and/or dissemination
• 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

Equal Opportunities

The University is an equal opportunities employer and welcomes applicants from all sections of the community, particularly from those with disabilities.

Appointment will be made on merit.

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 £19,237 (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