Hypertension, currently affecting 1 in 7 people in N. Ireland, is a major risk factor for cardiovascular disease, and in particular stroke. This project will investigate an epigenetic signature for hypertension and the effect of genotype and related B vitamins on this signature. 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 the MTHFR enzyme and this gene-nutrient interaction has been shown to play an important role in hypertension. Nutrients involved in one carbon metabolism such as riboflavin, therefore have the potential to influence DNA methylation. We have previously shown that intervention with riboflavin lowers blood pressure specifically in people with the TT genotype, independent of concurrent antihypertensive therapy. This project will investigate the epigenetic modifying effect of riboflavin to find new modifiable targets for hypertension treatment.
Please note: 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.
Please note, the successful candidate will be required to obtain AccessNI clearance prior to registration due to the nature of the project.
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.
If the University receives a large number of applicants for the project, the following desirable criteria may be applied to shortlist applicants for interview.
The University offers the following levels of support:
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 £18,000 (tbc) 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.
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.
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.
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 £8,000 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.
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.
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.
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.
The scholarship will cover tuition fees at the Home rate and a maintenance allowance of £18,000 (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.
Due consideration should be given to financing your studies. Further information on cost of living
1. Global BPgeu Consortium. Genome-wide association study of blood pressure and hypertension. Nat Gen. 2009, 41, 666
2. Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG et al. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase Nat Genet. 1995, 10, 111
3. Amenyah SD, Hughes CF, Ward M, Rosborough S, Deane J, Thursby SJ, Walsh CP, Kok DE, Strain JJ, McNulty H, Lees-Murdock DJ. Influence of nutrients involved in one-carbon metabolism on DNA methylation in adults-a systematic review and meta-analysis. Nutr Rev. 2020 Aug 1;78(8):647-666
4. Amenyah SD, Ward M, Strain JJ, McNulty H, Hughes CF, Dollin C, Walsh CP, Lees-Murdock DJ. Nutritional Epigenomics and Age-Related Disease. Curr Dev Nutr. 2020 Jun 6;4(7):nzaa097
5.Horigan G, McNulty H, Ward M, Strain JJ, Purvis J, Scott JM. Riboflavin lowers blood pressure in cardiovascular disease patients homozygous for the 677C-->T polymorphism in MTHFR. J. Hypertens. 2010, 28, 478
6. Wilson CP, Ward M, McNulty H, Strain JJ, Trouton TG, Horigan G, Purvis J, Scott JM. Riboflavin offers a targeted strategy for managing hypertension in patients with the MTHFR 677TT genotype: A 4-y follow-up. Am J Clin Nutr. 2012, 95:766–72.
7. Wilson CP, McNulty H, Ward M, Strain JJ, Trouton TG, Hoeft BA, Weber P, Roos FF, Horigan G, McAnena L, et al. Blood pressure in treated hypertensive individuals with the MTHFR 677TT genotype is responsive to intervention with riboflavin: Findings of a targeted randomized trial. Hypertension. 2013, 61:1302–8.
8. Ward et al. Impact of the common MTHFR 677C→T polymorphism on blood pressure in adulthood and role of riboflavin in modifying the genetic risk of hypertension: evidence from the JINGO project. BMC Med. 2020, 11;18(1):318.
9. Amenyah SD, McMahon A, Ward M, Deane J, McNulty H, Hughes CF, Strain JJ, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJ Riboflavin supplementation alters global and gene-specific DNA methylation in adults with the MTHFR 677 TT genotype. 2020, Biochimie 173, 17-26.
10. Amenyah SD, Ward M, McMahon A, Deane J, McNulty H, Hughes CF, Strain JJ, Horigan G, Purvis J, Walsh CP, Lees-Murdock DJ DNA methylation of hypertension-related genes and effect of riboflavin supplementation in adults stratified by genotype for the MTHFR C677T polymorphism 2021, International Journal of Cardiology 322, 233-239.
Submission deadline
Monday 27 February 2023
04:00PM
Interview Date
23 April 2023
Preferred student start date
18 September 2023
Telephone
Contact by phone
Email
Contact by email