PhD Study : Functional and health consequences of sub-optimal riboflavin status in adult populations across the lifecycle.

Summary

Rivoflavin or vitamin B2 is a water-soluble vitamin which is the pre-cursor for the flavocoenzymes flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). B2 plays a key role in energy production as well as interacting with a number of other nutrients, including Iron and, of particular interst to our group, the metabolically related B-vitamins.

Although not generally considered to be an issue in the developed world, because of the reliance on nutrition surveys to report status, sub-optimal riboflavin status appears to be more widespread in many populations than is generally recognised. Biomarker status is rarely measured because the existing biomarker EGRac requires very specific pre-analysis processing, unfeasible in most settings. A recent transnational  collaboration led by the supervisory team at NICHE  (DERiVE project: http://derive-riboflavin.com/ ) involving partners in Ireland (North and South) and Canada aims to address this gap by developing accessible riboflavin biomarkers for use in population surveys globally.

This PhD research project will extend this work by investigating important functional, gene-nutrient and health effects of optimal riboflavin status in different adult cohorts. The functional significance of sub-optimal riboflavin status is unclear. Among its metabolic roles, riboflavin is required (as FMN) to generate the active form of vitamin B6 in tissues. It has been shown previously that cells have a tendency to spare FAD at the expense of FMN; therefore, in the condition of riboflavin deficiency, the FMN-dependent pathways would be expected to be primarily affected.

This project will address this (Objective 1) by examining functional effects of changes of riboflavinstatus by measuring the response of vitamin B6 biomarker (plasma PLP) to interventions with riboflavin This will provide evidence that impaired riboflavin status may result in disturbance of vitamin B6 metabolic pathways with potential health consequences.

Hypertension is a major risk factor for CVD and is the strongest predictor of stroke risk. About 10% of the population carry a particular genetic factor [a common C677CT polymorphism in the folate metabolising enzyme methyltetrahydrofolate reductase (MTHFR)] that increases their risk of heart disease and stroke.  Furthermore, it has been shown that people who are homozygous for this polymorphism (TT genotype) are at increased risk of high blood pressure. Riboflavin is required as a co-factor for the MTHFR enzyme and in a series of novel studies conducted at this centre we demonstrated that riboflavin (1.6mg/d /16 weeks) significantly lowered blood pressure in premature CVD patients with the TT genotype and in hypertensive patients generally.

This PhD research project will further evaluate (Objective 2) the health benefit of riboflavin in modulating blood pressure via this novel gene-nutrient interactive effect in adults across the lifecycle.

The project will suit applicants who are highly motivated and willing to engage in teamwork and collaborative research with: excellent interpersonal skills; ability to work on own initiative;  excellent written and oral communication skills; ability to complete a project within a specified time; willingness to learn new skills and techniques, including laboratory skills; organisational skills and record keeping.

References

• HoriganG, 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. Journal of Hypertension 2010; 28: 478-486.
• McNulty H, Strain JJ Hughes CF, Ward M. Riboflavin, MTHFR genotype and blood pressure: A personalized approach to prevention and treatment of hypertension. Molecular Aspects of Medicine 2017; 53: 2-9.
• McMahon A, McNulty H, Hughes CF, Strain J.J, Ward M (2016). Novel approaches to investigate one-carbon metabolism and related B-vitamins in blood pressure. Nutrients 2016, 8, 720; doi:10.3390/nu8110720
• McAuley E, Hughes CF, McNulty H, Strain J.J, Ward M. (2016). Riboflavin, MTHFR genotype and blood pressure: Current evidence and implications for personalised nutrition. Proceedings of the Nutrition Society. 75 (3), pp. 405-414

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