Impact in incretin gene products on metabolic control

Summary

New and highly effective drugs for the treatment of obesity and diabetes, such as liraglutide (Victoza®, Saxenda®), semaglutide (Ozempic®, Wegovy®) and tirzepatide (Mounjaro®, Zepbound®) are fundamentally derived from the proglucagon and GIP genes.

Despite established effectiveness of these drugs, there are patient compliance issues relating to severe nausea, vomiting and other gastrointestinal type problems.

We believe a more thorough investigation of other products from the proglucagon and GIP genes, of which there are over ten different entities, could yield new drugs to enhance the effectiveness of these currently prescribed entities.

This project could help make drugs such as semaglutide and tirzepatide more amenable to patients and improve metabolic benefits in the real world setting.

The following research questions will be addressed as part of this research project:

1. What impact do proglucagon and GIP gene peptide products have on pancreatic beta-cell function? To answer this question, assessment of secretory and functional effects of all relevant peptide products on pancreatic alpha- and beta-cells will be conducted, with peptide combinations also to be considered.
2. Can long-acting enzyme resistant forms of proglucagon and GIP gene peptide products be generated? To resolve this matter, knowledge gained from question 1 will be used to design novel peptides with enzyme resistance, and bioactivity then assessed. The most promising analogue(s) will be progressed to single injection studies in animal models to examine impact on satiety and glucose homeostasis.
3. What impact will lead peptide combinations have on metabolic control? Preclinical therapeutic effectiveness of lead peptide combinations will be studied following sustained administration in models of obesity and diabetes.

Expected Results:  Discover treatment options to enhance the well-characterised benefits of currently approved drugs such as semaglutide and tirzepatide.

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

This project is funded by:

• Department for the Economy (DfE)

This scholarship will cover tuition fees and provide a maintenance allowance of £21,000* (tbc) per annum for three years (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of approximately £900 per annum is also available.

To be eligible for these scholarships, applicants must meet the following criteria:

• Be a UK National, or

• Have settled status, or

• Have pre-settled status, or

• Have indefinite leave to remain or enter, or

• be an Irish National

Applicants should also meet the residency criteria which requires that they have lived in the EEA, Switzerland, the UK or Gibraltar for at least the three years preceding the start date of the research degree programme.

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.

*Part time PhD scholarships may be available, based on 0.5 of the full time rate, and will require a six year registration period