Development of selective multi-agonist drugs for better metabolic disease management

Summary

Type 2 diabetes mellitus is frequently associated with obesity, impaired insulin secretion and reduced insulin sensitivity, resulting in persistent hyperglycaemia and an increased risk of cardiovascular and other disease complications.

There is a growing need for innovative therapies that simultaneously improve glycaemic control, promote weight loss and protect cardiovascular health.

Although current monotherapies can initially provide effective glucose control, disease progression often necessitates combination treatment. Multi-agonist peptide therapies offer a promising approach by targeting complementary metabolic pathways within a single molecule.

This project will investigate novel hybrid peptides to generate selective multi-agonist therapies for improved metabolic disease management.

Building on the demonstrated clinical benefits of multi-receptor agonism, we will develop and evaluate peptide analogues designed to activate complementary receptors involved in glycaemic control, appetite regulation, energy expenditure, insulin secretion and cardiovascular function.

Our previous studies demonstrated that the adipokine derived apelin-13 peptide analogues, acting through the APJ receptor, stimulate insulin secretion and reduce hyperglycaemia in diet-induced obese and diabetic db/db mice (O’Harte et al., 2018; 2020).

More recently, hybrid dual-agonist peptides incorporating apelin-13 demonstrated synergistic metabolic effects, including enhanced stability, stimulation of insulin secretion and reduced food intake compared with their individual component peptides (Sridhar et al., 2026).

We now aim to extend this approach by engineering novel multi- agonist peptides with selective combinations designed to maximise therapeutic efficacy while minimising undesirable effects.

The ultimate goal is to develop bioactive unimolecular multi-agonists capable of simultaneously improving glycaemic control, body weight, energy metabolism and cardiovascular health, providing a novel therapeutic strategy for the management of type 2 diabetes, obesity and associated cardiometabolic disease.

Please note:  Research Proposal - 5 pages in total

The proposal must include:

• Background to the project - 2 pages
• Problem to be addressed/Aim and Objectives - 1 page
• Methods to be used -1 page
• Anticipated outcomes -1 page
• List of references

Please also note that the use of AI in generating the research proposal is prohibited.

Important Information: Applications for more than one PhD studentship are welcome, however if you apply for more than one PhD project within Biomedical Sciences/Pharmacy and Pharmaceutical 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 detailing background, research questions, aims and methodology
• A comprehensive and articulate personal statement demonstrating interest in the subject area

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.

• Applicants should hold, or expect to hold a First Class Honours Degree in a relevant subject area
• Applicants should hold, or expect to hold a relevant Masters Degree at a level equivalent to commendation or distinction at Ulster
• Practice-based research experience and/or dissemination
• Experience or knowledge of research methods or other approaches relevant to the subject domain
• Work experience relevant to the proposed project
• 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)
• Vice Chancellor's Research Scholarship (VCRS)

PhD Scholarships are available for this project and will cover:

• Tuition fees.
• A maintenance allowance of approximately £22,000 (exact rate is to be confirmed) per annum for three years, subject to satisfactory academic performance.
• A Research Training Support Grant (RTSG) of approximately £900 per annum.

To be eligible for these scholarships applicants must: be a UK or Irish national; or have pre-settled or settled status; or have indefinite leave to remain or enter.

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 i.e. September 2027.

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, funded from any source, including self-financing students, are NOT eligible to apply for an award.

Students in full-time employment are not eligible for an award.

Due consideration should be given to financing your studies.

Part-time PhD scholarships may be available at a 0.5 pro rata rate of the full-time scholarship, which would require a six-year registration period.

The University will award a successful candidate one of the following scholarships for the project, depending on the funding available at the time an admissions offer is made:

1. Department for the Economy (DfE) PhD Scholarships
2. Vice Chancellor’s Research Scholarships (VCRS)

Please note that the Terms and Conditions for scholarships are subject to change for 2027/28.