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

This opportunity is now closed.

Subject: Biomedical Sciences

Summary

Hypertension is a major risk factor for cardiovascular disease affecting over 1 billion individuals worldwide leading to premature death. The 677TT genotype in MTHFR, has been identified as a risk factor for hypertension.  MTHFR, which is involved in one carbon metabolism, supplies methyl groups for regulation of gene expression by DNA methylation. Riboflavin is a co factor for MTHFR and this gene-nutrient interaction has been shown to play an important role in hypertension. 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. 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 poymorphisms

Essential Criteria

  • Upper Second Class Honours (2:1) Degree from a UK institution (or overseas award deemed equivalent via UK NARIC)
  • 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
  • Research project completion within taught Masters degree or MRES
  • 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

Funding

    Vice Chancellors Research Scholarships (VCRS)

    The scholarships will cover tuition fees and a maintenance award of £14,777 per annum for three years (subject to satisfactory academic performance). Applications are invited from UK, European Union and overseas students.

    DFE

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 14,777 per annum for three years. EU applicants will only be eligible for the fees component of the studentship (no maintenance award is provided).  For Non EU nationals the candidate must be "settled" in the UK.

Other information

The Doctoral College at Ulster University

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Key Dates

Submission Deadline
Monday 19 February 2018
Interview Date
6, 7 and 8 March 2018

Contact Supervisor

Dr Diane Lees Murdock

Other Supervisors

Apply online

Visit https://www.ulster.ac.uk/applyonline and quote reference number #238255 when applying for this PhD opportunity