PhD Study : Epigenetic Effects of Riboflavin Supplementation on Hypertension in Adults Screened for the MTHFR C677T Polymorphism

Summary

Hypertension is a major risk factor for cardiovascular disease affecting over 1 billion individuals worldwide [1] leading to premature death [2]. The 677TT genotype in MTHFR, has been identified as a risk factor for hypertension [3].  MTHFR, which is involved in one carbon metabolism, supplies methyl groups for regulation of gene expression by DNA methylation [4]. Riboflavin is a co factor for MTHFR and this gene-nutrient interaction has been shown to play an important role in hypertension [5]. We have previously shown that intervention with riboflavin lowers blood pressure specifically in people with the TT genotype, an effect that appears to be independent of concurrent antihypertensive therapy [6]. The mechanism by which riboflavin regulates hypertension is not clear but it is apparent that other factors in addition to genotype are influencing this effect.

This project will examine how MTHFR genotype influences genome-wide DNA methylation in participants screened for the MTHFR TT genotype. Furthermore, the candidate will investigate if DNA methylation is altered as a result of riboflavin supplementation to gain an understanding of the blood pressure lowering mechanism of riboflavin.

The findings of this study will provide important information regarding the mechanism linking this novel gene-nutrient interaction with hypertension. Our hypothesis is that the TT genotype is associated with epigenetic changes which render individuals susceptible to high BP.  Riboflavin supplementation alters DNA methylation at key loci in TT individuals.

Our aims are to:

(i)  Investigate the influence of riboflavin on the epigenetic machinery using molecular biology methods.

(ii) Investigate the role of epigenetic machinery in methylation changes regulated by riboflavin using targeted disruption of the catalytically active DNA methyltransferase enzymes using CRISPR/Cas9 in various model systems.

(iii) bioinformatic analysis of extant data to analyse DNA methylation in individuals with MTHFR polymorphisms.

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

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
• Masters at 65%
• Research project completion within taught Masters degree or MRES
• 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 - peer-reviewed
• Experience of presentation of research findings
• A comprehensive and articulate personal statement
• Relevant professional qualification and/or a Degree in a Health or Health related area

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 £19,000 (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