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Developing microbiological ammunition for robust decolonization of antibiotic resistant bacteria.

University of Exeter - College of Life and Environmental Sciences.

Qualification Type: PhD
Location: Penryn
Funding for: UK Students, EU Students
Funding amount: BBSRC SWBio DTP funded CASE studentship available for September 2022 entry. The studentship will provide funding of fees and a stipend which is currently £15,609 per annum for 2022-23, on a full time basis.
Hours: Full Time
Placed On: 22nd October 2021
Closes: 6th December 2021
Reference: 4279

"Taking antibiotics is not risk free. For a year after completing a course, there is an increased risk of complex infection from antimicrobial-resistant microbes, and individuals colonized with resistant microbes can transmit them freely to others for extended periods. 

These resistant bacteria are likely to be gut-dwelling commensals.  Commensal bacteria make up most of the highly problematic multi-drug resistant microbes, and tackling the persistence of resistant commensals will be a key part of future antimicrobial stewardship and overall reduction in drug-resistant infections 1.    

This project will explore how we might efficiently replace resistant Escherichia coli in the gut with harmless commensals by exploiting selective bacteriophage as phage therapy. Using novel experimental models, such as gut organoids, we aim to optimize these ‘decolonization’ strategies and develop approaches that are resilient to the evolution of phage resistance.   Escherichia coli is a good target for this decolonization since one lineage (the ST 131 clonal complex) is responsible for a large proportion of multi-drug resistant infections, including life-threatening bacteraemia. The supervisors have already developed an efficient pipeline for isolating lineage specific phage as well as techniques (increasing within-species competition) that can make decolonization more effective. 

Using this pipeline and an existing phage collection the student will develop diverse phage cocktails with the aim of displacing bacteria without producing widespread phage resistance in target E. coli genotypes.  In addition, the student will isolate and sequence phage resistant E. coli in order to better understand the genetic basis of phage resistance to major phage families and test the efficacy of decolonization in simple in vivo models (insects, organoids). We also predict that broad-spectrum phage resistance might have severe fitness consequences for E. coli, especially in complex communities or under the harsher conditions in the gut, so the fitness consequences of phage resistance will also be explored in simple and diverse communities.     

This is a multi-disciplinary project providing training in microbiology, evolutionary biology and bioinformatics with significant impacts on how we manage drug resistant and life-threatening infections. A successful student will gain important laboratory and analytical skills with infection models and microbial bioinformatics. 

The team have expertise in bioinformatics, phage resistance and displacement of antibiotic resistant bacteria 2,3,4 and have a wide range of experience that could match the interests of diverse applicants.    

Eligibility 

To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria. 

A fully-funded four year SWBio DTP studentship will cover 

  • a stipend* at the standard Research Council UK rate; currently £15,609 per annum for 2022-23
    •    research and training costs 
    •    tuition fees (at the standard Research Councils UK rate) 
    •    additional funds to support fieldwork, conferences and a 3-month internship 

Please refer to the regulations or Annex 1 of the Research Council Training Grant Guide to confirm that you meet the residence criteria for a fully-funded studentship.  Any further queries in relation to residency must be directed to the institution that you are applying to. 

* An enhanced stipend is available for students with a recognised veterinary degree qualification (£24,090 per annum for 2022-2023). There may also be enhanced stipends associated with projects that have a CASE partner (CASE projects are highlighted as *CASE in the project lists). 

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