Rational design and preclinical evaluation of unimolecular multi-agonist peptide therapeutics for obesity and related metabolic disease

Summary

The success of GLP-1-based medicines such as semaglutide, as well as related and multi-agonist drugs such as tirzepatide, has demonstrated the therapeutic potential of targeting multiple metabolic pathways to treat obesity and related disease. However, there remains considerable scope to develop new peptide therapeutics with improved efficacy, duration of action, tolerability and metabolic benefits. Thus, whilst semaglutide and tirzepatide are effective, they are also no without considerable side effects and drawbacks for patients.

This project will investigate the rational design and preclinical evaluation of novel unimolecular multi-agonist peptides, in which the biological activities various metabolically important peptide hormones are incorporated into a single therapeutic entity.

Rather than focusing on a predetermined peptide combination, the project will draw on a broad portfolio of gut and endocrine peptides already studies at Ulster, including but not limited to GLP-1, GIP, glucagon, xenin, CCK, kisspeptin, oxyntomodulin, GLP-2, oxytocin, PYY and pancreatic polypeptide, to identify combinations with complementary therapeutic properties.

Importantly, the project will combine computational molecular modelling and peptide design with in vitro pharmacological characterisation and preclinical evaluation.

The following research questions will be addressed:

1.Can computational modelling and rational peptide engineering be used to generate stable unimolecular multi-agonists with appropriate receptor activity and pharmacological properties?
2.How do lead unimolecular multi-agonists compare with their individual components and established peptide therapeutics in cellular and animal models?
3.Can lead candidates demonstrate enhanced therapeutic efficacy in preclinical models of obesity and related metabolic disease?

The project will provide interdisciplinary training across computational peptide design, molecular modelling, peptide chemistry, receptor pharmacology and preclinical drug development, through collaboration between Ulster University and the University of Limerick.

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.