Primary Supervisor: Dr Paul Kroon - email@example.com
Secondary Supervisor: Arjan Narbad (QIB)
The human gut microbiota is actively involved in the metabolism of dietary compounds, often into metabolites that benefit the host (e.g. short-chain fatty acids). However, the gut microbiota-dependent formation of trimethylamine (TMA) from L-carnitine and choline results in an atherogenic metabolite, TMA-N-oxide (TMAO). Plasma TMAO levels are strongly associated with several causes of death (e.g. heart failure) and with diseases such as diabetes, Alzheimer's and chronic kidney disease. There is no effective, sustainable treatment for reducing TMA(O) levels. But, we have recently shown substantial inhibition of gut microbial L-carnitine metabolism by a pomegranate product. The aim of this studentship is to develop a mechanistic understanding of how the pomegranate compounds interact with the gut microbiota and inhibit their ability to metabolise carnitine and generate TMA(O).
We have recently shown that an in vitro model of the human colon authentically replicates the metabolism of Lcarnitine and choline observed in vivo (Day Walsh et al., 2021), and the student will use this to investigate (1) which compounds in pomegranate inhibit L-carnitine metablism to TMA and (2) understand the mechanisms of action. The student will receive training in using colon models to investigate L-carnitine metabolism, shotgun metagenomics and bioinformatics analysis of gut microbiota communities, PCR and qRT-PCR assays for target microbial genes, and use of LC-MS/MS and LC-TOF-MS platforms for analysing polyphenol and L-carnitine metabolites.
This project will suit a student interested in fundamental research that links gut microbiota and health, and in undertaking pre-clinical work that is highly translational. The student will join the Kroon group in the Food Innovation and Health Programme and work closely with the Narbad group (expertise in gut microbial ecology). The Quadram Institute is part of the Norwich Research Park and is home to a large cohort of PGR students and researchers.
The Norwich Research Park Biosciences Doctoral Training Partnership (NRPDTP) is open to the UK and international candidates for entry in October 2022 and offers postgraduates the opportunity to undertake a 4-year PhD research project whilst enhancing professional development and research skills through a comprehensive training programme. You will join a vibrant community of world-leading researchers.
All NRPDTP students undertake a three-month professional internship placement (PIPS) during their study. The placement offers exciting and invaluable work experience designed to enhance professional development. Full support and advice will be provided by our Professional Internship team. Students with, or expecting to attain, at least an upper second class honours degree, or equivalent, are invited to apply.
This project has been shortlisted for funding by the NRPDTP programme. Shortlisted applicants will be interviewed on Tuesday 25th January, Wednesday 26th January and Thursday 27th January 2022.
You can visit the Norwich Research Park Biosciences Doctoral Training Partnership for further information on eligibility and the application process.
Our partners value diverse and inclusive work environments that are positive and supportive. Students are selected for admission without regard to gender, marital or civil partnership status, disability, race, nationality, ethnic origin, religion or belief, sexual orientation, age or social background.