PhD Studentship: The Double Life of E. Coli as Benign Commensal and Deadly Pathogen: the COHORT-Microbiome Study

Location: John Radcliffe Hospital

Background

Escherichia coli is a common and usually benign constituent of the human gut microbiome but is also a leading cause of urinary tract and bloodstream infection associated with substantial morbidity and mortality. We have shown that despite there being many thousands of known sequence types of E. coli, just four cause ~50% of bloodstream infections in England. Despite intensive genomic surveillance of invasive E. coli isolates (e.g. from bloodstream infections), comparatively little is known about the molecular epidemiology of commensal strains. We want to find out whether these strains are better at causing invasive disease (i.e. more pathogenic) or simply have more opportunities to do so because they are better at colonising and persisting in the gut.

Project overview

This project will form part of a unique study being run in collaboration with the Oxford Vaccine Group and Ellison Institute of technology. The COHORT study (PI Prof Susanna Dunachie) seeks to understand immunological responses to E. coli in patients across a spectrum from health to disease. COHORT-Microbiome will add longitudinal faecal sampling to investigate longitudinal microbiome profiles in this same group of participants.

The student will generate unique, high-quality genomic datasets using long-read sequencing facilities available within our unit. They will then link these with highly granular clinical metadata from electronic healthcare records. Using recently developed bioinformatic methodologies for strain deconvolution in long-read metagenomic samples, they will generate unprecedented insights into the colonisation dynamics of E. coli in patients at risk of invasive disease and compare this to healthy controls. The student will then use this data to explore the association between the ecology of E. coli in the context of the wider microbiome and future infection risk.

The student will have the opportunity to test specific hypothesis arising from COHORT-Microbiome in the lab by performing in vitro studies to investigate in more detail the interaction between strain colonisation dynamics, microbiome background and antibiotic exposure. We anticipate that there will also be opportunities for further collaborative work to perform a joint exploratory analysis of the combined microbiome and immunological datasets.

Ultimately the insights generated from this project will help to shape our understanding of the ecology of an important human pathogen and inform the design of much needed interventions to reduce the burden of disease associated with it. The project would suit an ambitious student who is keen to develop skills across both the wet and dry labs and work within an inter-disciplinary team to apply these to an important clinical problem.

Funding Details

Funding Minimum: Home fees student

Funding Maximum: International student (subject to gaining an NDM studentship)