The human large bowel contains ~1013 bacteria, referred to as the human gut microbiota or HGM. There is considerable interest in deploying prebiotic and probiotic strategies to maximise the impact of the HGM on human health. The major nutrients available to the HGM are dietary and host glycans. Understanding how these complex carbohydrates are metabolised by the HGM is critical to developing novel and effective prebiotic and probiotic strategies that maximise the health benefits of this ecosystem. Recent studies, however, have shown the extinction of key organisms in HGMs of individuals that consume highly processed diets. The repopulation of these HGMs with appropriate organisms requires knowledge of the glycans utilised by these bacteria to underpin dietary strategies that encourage the re-establishment of these microorganisms in the human gut. Thus, the repopulation of these bacteria requires the identification of privileged glycans, which, in the context of the HGM, are used exclusively by specific organisms. The extensive variation in the glycan component of arabinogalactan proteins (AGPs) could, potentially, offer novel prebiotic opportunities. Preliminary data has provided insights into how dietary AGPs are utilized by the HGM Bacteroides species. The data showed i) A small number of keystone organisms make some complex AGPs generally available to the HGM. ii) In contrast, a wine derived AGP is utilised by a single Bacteroides species (B. plebeius), and thus this glycan may represent a much sought after privileged nutrient that could re-establish organisms in the HGM. The PhD will dissect the mechanism by which B. plebeius utilises the wine AGP, and extend our knowledge of the variation in AGP degrading systems found within the Bacteroides members of the HGM. The microbiological relevance of the biochemical data will be evaluated through cross-feeding experiments, to explore the selectivity of thus glycans as growth substrates within the HGM. Finally, the project will test the hypothesis that wine AGP is a privileged nutrient within the HGM, which can be exploited to repopulate these ecosystems with selected bacteria.
Eligibility and How to Apply:
Please note eligibility requirement:
• Academic excellence of the proposed student i.e. 2:1 (or equivalent GPA from non-UK universities [preference for 1st class honours]); or a Masters (preference for Merit or above); or APEL evidence of substantial practitioner achievement.
• Appropriate IELTS score, if required.
For further details of how to apply, entry requirements and the application form, see https://www.northumbria.ac.uk/research/postgraduate-research-degrees/how-to-apply/
Please note: Applications should include a covering letter that includes a short summary (500 words max.) of a relevant piece of research that you have previously completed. Applications that do not include the advert reference (e.g. RDF18/…) will not be considered.
Deadline for applications: 1st July 2019 for October 2019 start, or 1st December 2018 for March 2019 start
Start Date: October or March
Northumbria University takes pride in, and values, the quality and diversity of our staff. We welcome applications from all members of the community. The University holds an Athena SWAN Bronze award in recognition of our commitment to improving employment practices for the advancement of gender equality and is a member of the Euraxess network, which delivers information and support to professional researchers
• An evolutionarily distinct family of polysaccharide lyases removes rhamnose capping of complex arabinogalactan proteins. Muñoz-Muñoz, J.L.; Cartmell, A.; Terrapon, N.; Henrissat, B. and Gilbert, H.J. Journal of Biological Chemistry. 292 (32) 13271-13283. 2017.
• Unusual active-site location and catalytic apparatus in a glycoside hydrolase family. Muñoz-Muñoz, J.L.; Cartmell, A.; Terrapon, N.; Henrissat, B. and Gilbert, H.J. Proceedings of the National Academy of Sciences of the United States of America. PNAS. 114 (19) 4936-4941. 2017
• Human Gut Bacteroidetes can utilize yeast mannan through a selfish mechanism. Cuskin F.; Lowe E.C.; Temple M.J.; Zhu Y.; Cameron E.A.; Pudlo N.A.; Porter N.T.; Urs K.; Thompson A.J.; Cartmell A.; Rogowski A.; Hamilton B.S.; Chen R.; Tolbert T.J.; Piens K.; Bracke D.; Vervecken W.; Hakki Z.; Speciale G.; Muñoz-Muñoz, J.L.; Day A.; Peña M.J.; McLean R.; Suits M.D.; Boraston A.B.; Atherly T.; Ziemer C.J.; Williams S.J.; Davies G.J.; Abbott D.W.; Martens E.C.; Gilbert H.J. Nature. 517 (7533) 165-169. 2015.