Defining the physiological role and regulation of biological methylations

The regulation of gene expression and function operates at multiple levels. Metabolic pathways in the cell generate metabolites that directly affect DNA, RNA and proteins, regulating the expression and function of many genes, often feeding back on the very enzymes that catalysed their synthesis. The precursors of these key regulatory metabolites, or the key metabolites themselves, are usually obtained from the diet. Thus, in our body there is an intimate integration between our diet, our physiology and behaviour, and yet, how this integration operates remains obscure in many ways. What is clear is that, when the link between essential nutrients and gene expression is disrupted, pathologies including cardiovascular diseases, diabetes, cancer and neurological problems arise.

This project is seeking to define how the essential amino acid methionine and vitamin B9 regulate our physiology and behaviour. These two nutrients can regulate gene expression and function by acting on DNA and proteins by a mechanism known as methylation, i.e. the addition of a methyl group to specific nucleotides or amino acids. Methylated nucleotides can also be found on RNAs, but whether and how this methylation can be regulated, and whether it is affected by our diet is unknown. Our previous investigations have revealed that methyl metabolism, and especially mRNA methylation, is critical for biological rhythms in organisms throughout evolution, from bacteria to humans. The project will use these discoveries as a starting point to investigate the physiological function of RNA methylation, how it is regulated by our diet, and what pathologies arise when it is disrupted.

Eligibility

Applicants must 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 a relevant discipline.

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How to Apply

For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.

For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team admissions.doctoralacademy@manchester.ac.uk

Equality, Diversity and Inclusion

Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/

For international students we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit http://www.internationalphd.manchester.ac.uk