Epigenetic Mechanisms of Blood Pressure Reduction in Obese, Non-Diabetic Patients: Identifying Novel Targets for Antihypertensive Therapy

Summary

Epigenetic modifications, including DNA methylation, influence gene regulation involved in hypertension (high blood pressure). This project aims to investigate specific epigenetic changes in obese, non-diabetic individuals undergoing structured weight loss interventions (both surgical and pharmacological e.g. Ozempic, Wegovy). Obesity is a major risk factor for hypertension, yet not all obese individuals exhibit the same blood pressure profiles, suggesting epigenetic factors may influence their cardiovascular risk. However, limited research has explored the specific epigenetic changes that occur in non-diabetic, obese individuals during weight loss and how these might serve as targets for antihypertensive interventions. Understanding these changes can offer insight into novel epigenetic targets for managing hypertension associated with obesity.

This project will recruit obese, non-diabetic adults undergoing different surgical and pharmacological weight loss interventions who will undergo clinical assessment and blood sample collection at baseline, post-intervention and one year follow-up. Epigenetic profiling will examine DNA methylation focusing on genes regulating vascular tone, inflammation and endothelial function.  Bioinformatic analysis will be used to detect changes in biological age following treatments and correlate epigenetic data with blood pressure and metabolic profiles. Machine learning models will identify specific epigenetic signatures predictive of improved blood pressure control following weight loss, and pathway analysis will highlight potential therapeutic targets.  Identified epigenetic changes will be functionally validated in vascular smooth muscle cell models to determine their impact on blood pressure-regulating genes. Pharmacological modulation of these epigenetic markers will be tested to assess their potential as antihypertensive targets.

This study aims to advance our understanding of how epigenetic changes influence blood pressure and identify novel epigenetic targets for antihypertensive therapies and development of a more personalized approach to hypertension management in obese individuals.

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)
• Vice Chancellor's Research Scholarship (VCRS)

Our fully funded PhD scholarships will cover tuition fees and provide a maintenance allowance of £19,237 (tbc) per annum for three years (subject to satisfactory academic performance).  A Research Training Support Grant (RTSG) of £900 per annum is also available.

These scholarships, funded via the Department for the Economy (DfE) and the Vice Chancellor’s Research Scholarships (VCRS), are open to applicants worldwide, regardless of residency or domicile.

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.