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(MRC DTP) The oral microbiome, microbial metabolites and their impact upon local and systemic immunity

  • Full or part time
  • Application Deadline
    Friday, November 15, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Commensal microbes and the host immune system have formed an evolutionary partnership that is vital for the development, metabolism and defensive immunity of the host. This commensal microbial community produces a plethora of factors capable of regulating the host immune system, ensuring effective immunity should pathogenic challenge occur but also reinforcing a peaceful coexistence with the resident commensal microbes. A mounting body of evidence indicates that microbial metabolites are capable of functionally regulating the host immune system both locally at the site of commensal colonisation, but also systemically at distal sites. Therefore a “healthy” microbial commensal community generates metabolites that are essential for the correct functional calibration of immune cells and subsequently, local and systemic immune responses. As such, alterations in commensal-derived metabolites influences the host’s susceptibility to multiple auto-inflammatory conditions and disorders; highlighting microbial metabolites as essential mediators of the host-commensal microbe dialog which have profound effects on immune health.

Much of the data concerning the impact of microbial metabolites on immune health have focused on those generated by the microbial communities of the gastrointestinal tract. However, the oral commensal community produces a wide variety of metabolites that could well impact immune functioning. Moreover, the metabolite output from the oral commensals is well established to change substantially during the oral inflammatory disease Periodontitis, the most common chronic inflammatory condition of mankind. Understanding how oral commensal-derived metabolites calibrate immune cell function and how this changes during periodontitis therefore represents a novel therapeutic avenue for the treatment of oral, and potentially systemic, inflammatory diseases.

The aim of this project is to mechanistically understand how metabolites derived from oral microbes impact local (oral) and systemic immune functions. This project will employ gnotobiotic (germ free) animals, ex vivo immune cell assays, alongside pioneering in vitro microbiology approaches to generate an unprecedented insight into the immune modifying activities of oral commensal-derived metabolites. Given the interdisciplinary nature of this project undertaking these studies will lead to training in many cutting-edge techniques including: high-dimensional flow-cytometry, in vitro Biofilm models, in vivo models of inflammation and RNA/DNA-sequencing and bioinformatics analysis. Ultimately, data generated within this project will be the first to delineate mechanisms of immune control mediated by metabolites generated by the oral commensal community outlining how these metabolites to contribute to both local and systemic inflammation.

https://www.research.manchester.ac.uk/portal/andrew.mcbain.html
https://www.research.manchester.ac.uk/portal/joanne.konkel.html
https://www.bmh.manchester.ac.uk/research/domains/infection-immunity-inflammation-repair/immunology/

Twitter: @grainger_konkel

Entry Requirements:
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found on the MRC DTP website View Website

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

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