About the Project
Ageing is associated with a decline in nitric oxide (NO) production via NO synthase (NOS) enzymes, which contributes to impairment of cardiovascular health and functional capacity. Dietary nitrate, which can be converted to NO without NOS in the human body, is a potential intervention to compensate for reduced NOS function. A critical step in the bio-activation of ingested nitrate is its reduction to nitrite by commensal anaerobic bacteria in the oral cavity. Vegetable-rich diets (e.g. ‘5-a-day’) that are naturally high in inorganic nitrate are known to exert several beneficial effects on cardiovascular health. Accumulating evidence suggests that the cardiovascular benefits of high vegetable intake may be related to the high nitrate content of these foodstuffs, but alterations in the oral microbiome with ageing and diet may mean that some individuals gain limited benefit from adhering to these dietary guidelines. However, the relationships between commensal nitrate-reducing oral bacteria, NO bioavailability and cardiovascular health are largely unknown.
We, and others, have shown that dietary nitrate reduces blood pressure in older people and has beneficial effects on oxygen utilisation during low-intensity exercise, which is a characteristic of typical tasks of daily life. We also know that there are large inter-individual variations in the physiological responses to nitrate supplementation, irrespective of age. It is conceivable that such variation could be linked to the abundance of nitrate-reducing bacteria in the oral microbiota. Identification of ‘good’ and ‘bad’ oral bacteria (which facilitate or hinder, respectively) nitrate reduction may enable development of probiotic and prebiotic interventions to maximize the cardiovascular benefit of the symbiosis between the oral microbiota and its human host.
The PhD programme centers on the hypothesis that the oral microbiota modulates the nitrate-reduction capacity, and therefore, the cardiovascular benefits that can be gained from a nitrate-rich diet. The aim of this PhD programme is to investigate the relationship between the oral microbiota and NO bioavailability and bioactivity in young and older adults.
We seek an aspiring student with an interest in the human microbiome and healthy aging. As a member of an interdisciplinary research team, the successful candidate will master a range of experimental techniques including large-scale next generation gene sequencing and bioinformatics analyses, biochemical methods for assessment of NO bioavailability and nitrate reductase activity, and physiological assessments of cardiovascular function and exercise capacity. The student will develop skills in data handling and analyses, and manuscript preparation.
Academic Supervisors:
Prof Andy Jones, Sport & Health Sciences, St Luke’s Campus, Exeter
Dr Mark van der Giezen, Biosciences, Streatham Campus, Exeter
Prof Paul Winyard, University of Exeter Medical School
Location: University of Exeter, St Luke’s Campus, Exeter
About the award:
This project is one of a number which are funded within the Carlota Palmer PhD programme. This four-year programme, run under the auspices of the Centre for Biomedical Modelling and Analysis, will commence in September 2016. The studentships will provide funding for a stipend (currently £16,165 per annum), research costs and UK/EU tuition fees for four years. Further details can be found here: http://www.exeter.ac.uk/bma/phd/
Entry requirements:
Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science or technology. Applicants with a Lower Second Class degree will be considered if they also have Master’s degree or have significant relevant non-academic experience. If English is not your first language you will need to have achieved at least 6.5 in IELTS (and no less than 6.0 in any section) by the start of the project (alternative tests may be acceptable, see http://www.exeter.ac.uk/postgraduate/apply/english/).
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