This opportunity is now closed.

Funded PhD Opportunity

Role of B-vitamins in Epigenetic Modulation of Hypertension

Subject: Biomedical Sciences


Summary

Hypertension, currently affecting 1 in 7 people in N. Ireland, is a major risk factor for cardiovascular disease, and in particular stroke. The 677TT genotype in MTHFR, carried by 10% of people in Northern Ireland, 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, 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.

We have recently demonstrated, in NICHSA funded work, that DNA methylation differs in individuals stratified by their MTHFR genotype and is altered both globally and at key loci related to hypertension in TT individuals receiving riboflavin in randomised control trials.  In initial epigenome-wide exploratory analysis comparing methylation in peripheral blood samples from 16 MTHFR TT individuals, 94.5% of the top 1000 genomic regions gained methylation in individuals following supplementation with riboflavin.

We now propose to extend this genome-wide DNA methylation analysis to gain further 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.

Hypothesis and aims of project;

The overarching aim is to examine the effect of riboflavin (vitamin B2) on DNA methylation in hypertensive adults with the MTHFR 677TT genotype to gain an understanding of the role of riboflavin in blood pressure regulation and identify novel targets for hypertension treatment.

Hypothesis;

The MTHFR 677TT genotype is associated with DNA methylation patterns which render individuals susceptible to high BP.  Riboflavin supplementation alters DNA methylation at key loci related to hypertension in TT individuals

Aims;

1.Assess genome-wide DNA methylation patterns of peripheral blood lymphocytes collected from randomised control trials of riboflavin supplementation specifically in individuals with the MTHFR 677TT genotype using Illumina EPIC array

2.Confirm DNA methylation changes at key loci identified using pyrosequencing

3.Investigate our findings in an independent dataset

4.Examine the role of DNA methylation in controlling gene expression at novel riboflavin-sensitive loci using DNMT knockout cell lines


Essential criteria

  • To hold, or expect to achieve by 15 August, an Upper Second Class Honours (2:1) Degree or equivalent from a UK institution (or overseas award deemed to be equivalent via UK NARIC) in a related or cognate field.
  • 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.

  • Completion of Masters at a level equivalent to commendation or distinction at Ulster
  • Experience using research methods or other approaches relevant to the subject domain
  • Work experience relevant to the proposed project
  • Publications - peer-reviewed
  • Publications record appropriate to career stage
  • Experience of presentation of research findings
  • A comprehensive and articulate personal statement
  • Use of personal initiative as evidenced by record of work above that normally expected at career stage.
  • Relevant professional qualification and/or a Degree in a Health or Health related area

Funding

    The University offers the following awards to support PhD study and applications are invited from UK, EU and overseas for the following levels of support:

    Vice Chancellors Research Studentship (VCRS)

    Full award (full-time PhD fees + DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £15,000 maintenance grant 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.

    Vice-Chancellor’s Research Bursary (VCRB)

    Part award (full-time PhD fees + 50% DfE level of maintenance grant + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees and provide the recipient with £7,500 maintenance grant 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.

    Vice-Chancellor’s Research Fees Bursary (VCRFB)

    Fees only award (PhD fees + RTSG for 3 years).

    This scholarship will cover full-time PhD tuition fees 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.

    Department for the Economy (DFE)

    The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £ 15,009 per annum for three years. EU applicants will only be eligible for the fee’s component of the studentship (no maintenance award is provided). For Non-EU nationals the candidate must be "settled" in the UK. 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.

    Due consideration should be given to financing your studies; for further information on cost of living etc. please refer to: www.ulster.ac.uk/doctoralcollege/postgraduate-research/fees-and-funding/financing-your-studies


Other information


The Doctoral College at Ulster University


Reviews

Profile picture of Kieran O'Donnell

My experience has been great and the people that I have worked with have been amazing

Kieran O'Donnell - 3D printing of biological cells for tissue engineering applications

Watch Video  

Profile picture of Michelle Clements Clements

Completing the MRes provided me with a lot of different skills, particularly in research methods and lab skills.

Michelle Clements Clements - MRes - Life and Health Sciences

Watch Video  

Profile picture of William Crowe

Throughout my PhD I’ve been provided with continuous support and guidance by my supervisors and the staff at the University.I’ve also received many opportunities to further enhance my professional development in the form of teaching experience and presenting my work at conferences which will aid in my pursuit of a career in academia or industry.

William Crowe


Key dates

Submission deadline
Friday 7 February 2020

Interview Date
09 to 20 March 2020


Applying

Apply Online  


Campus

Coleraine campus

Coleraine campus
The feeling of community at our Coleraine campus makes for a warm and welcoming student experience.


Contact supervisor

Dr Diane Lees Murdock


Other supervisors

Related Funded Opportunities

Diabetes

Subject: Biomedical Sciences

 View details

The regulation of rhamnolipid biosynthesis in Burkholderia thailandensis.

Closing date:
Tuesday 1 September 2020
Subject: Biomedical Sciences

 View details

Genomic Medicine

Subject: Biomedical Sciences

 View details

Stratified Medicine

Subject: Biomedical Sciences

 View details

Novel amphibian skin peptide-analogues for the treatment of type-2 diabetes

Closing date:
Friday 18 September 2020
Subject: Biomedical Sciences

 View details

The production of rhamnolipid biosurfactant by Pseudomonas aeruginosa growing in biofilms.

Closing date:
Tuesday 1 September 2020
Subject: Biomedical Sciences

 View details

Optometry and Vision Science

Subject: Biomedical Sciences

 View details

MRes in Biomedical Sciences

Subject: Biomedical Sciences

 View details