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How does the human gut microbiota protect against infection with enterohaemorrhagic E. coli? (SchullerS-NarbadAU19SF)


Project Description

The human body is populated by trillions of commensal bacteria (microbiota), most of which reside in the intestine and have established a symbiotic relationship with the host. While the human gut environment provides the bacteria with nutrients, the microbiota enhances the metabolism of polysaccharides and produces essential vitamins.

In addition, it modulates the immune system and protects the host against enteric infections (colonisation resistance). While it is well established how enteropathogenic bacteria interfere with intestinal function, the underlying molecular mechanisms of how the microbiota counteracts these influences and protects the host remain largely unknown. This is mainly due to a lack of experimental human intestinal model systems supporting the growth of gut commensal bacteria which are mostly sensitive to oxygen and rely on mucus-derived sugars as nutrient sources.

We have recently developed a novel Vertical Diffusion Chamber (VDC) system which enables us to co-culture human mucus-producing gut epithelia with strictly anaerobic microbiota species. In this project, we will apply the VDC system to determine the interactions of a complex gut microbiota with human intestinal epithelium and the serious foodborne pathogen enterohaemorrhagic E. coli (EHEC aka E. coli O157), the major cause of acute kidney failure in children. This will be achieved by employing anaerobic bacterial culture, analysis of the microbiota diversity by 16S rRNA sequencing, growth of human intestinal model epithelia in a VDC system, molecular and protein biology, and confocal/electron microscopy. Findings from this work will lead to a better understanding how the gut microbiota protects against EHEC infection and why some people are more susceptible to disease than others.

The PhD student working on this project will benefit from the stimulating and multi-disciplinary environment at the Norwich Research Park and will be supervised by research groups at the Norwich Medical School (Schüller) and the Quadram Institute (Narbad).

For more information on the project’s supervisor, please visit: https://people.uea.ac.uk/en/persons/s-schuller
Type of programme: PhD
Start date of project: October 2020
Mode of study: full time
Studentship length: . 3 year studentships have a (non-funded) 1 year ‘registration only’ period
Location: Bob Champion Research & Education Building (BCRE), Norwich Research Park, Colney Ln, Norwich, NR4 7UQ

ENTRY REQUIREMENTS:
A minimum upper second class in their first undergraduate degree (or equivalent) in Biological or Biomedical Sciences.

Funding Notes

This PhD project is offered on a self-funding basis. It is open to applicants with funding or those applying to funding sources. Details of tuition fees can be found at View Website.

A bench fee may also payable on top of the tuition fee to cover specialist equipment or laboratory costs required for the research. The amount charged annually will vary considerably depending on the nature of the project and applicants should contact the primary supervisor for further information about the fee associated with the project.

References

(i) Schüller S and Phillips AD (2010) Microaerobic conditions enhance type III secretion and adherence of enterohaemorrhagic Escherichia coli to polarized human intestinal epithelial cells. Environ Microbiol 12:2426-35.

(ii) Hews CL, Tran SL, Wegmann U, Brett B, Walsham AD, Kavanaugh D, Ward NJ, Juge N, and Schüller S (2017) The StcE metalloprotease of enterohaemorrhagic Escherichia coli reduces the inner mucus layer and promotes adherence to human colonic epithelium ex vivo. Cell Microbiol 19: e12717.

(iii) Lewis SB, Cook V, Tighe R, and Schüller S (2015) Enterohemorrhagic Escherichia coli colonization of human colonic epithelium in vitro and ex vivo. Infect Immun 83:942-9.

(iv) Kellingray L, Le Gall G, Defernez M, Beales I, Franslem-Elumogo N, Narbad A (2018) Microbial taxonomic and metabolic alterations during faecal microbiota transplantation to treat Clostridium difficile infection. Journal of Infection 77:107–118.

(v) Garcia Gutierrez E, Mayer MJ, Cotter PD, Narbad A (2018) Gut microbiota as a source of novel antimicrobials. Gut microbes. 27:1-21.

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