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CRISPR-Cas9 gene drives to eradicate antimicrobial resistance from bacterial communities. PhD in Biosciences (SWBio DTP)

  • Full or part time
  • Application Deadline
    Monday, December 02, 2019
  • Competition Funded PhD Project (European/UK Students Only)
    Competition Funded PhD Project (European/UK Students Only)

Project Description

Lead Supervisor
Dr Stineke van Houte, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter

Additional Supervisors
- Dr Ben Ashby, Department of Mathematical Sciences, University of Bath
- Professor Edze Westra, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
- Prof Will Gaze, College of Medicine and Health, University of Exeter

Location: University of Exeter, Penryn Campus, Penryn, Cornwall, TR10 9FE

Programme Overview
The South West Biosciences Doctoral Training Partnership (SWBio DTP http://www.swbio.ac.uk/) is led by the University of Bristol, together with the Universities of Bath, Cardiff and Exeter, alongside Rothamsted Research. This partnership also includes the following collaborative partners; Marine Biological Association (MBA), Plymouth Marine Laboratory (PML), Swansea University, UCB Pharma, University of the West of England (UWE) and SETsquared Bristol.

These institutions represent a distinctive group of bioscience research staff and students, with established international, national and regional networks, and widely recognised research excellence. As research leaders, we have a strong track record in advancing knowledge through high-quality research and teaching, in partnership with industry and the government.

For more information about the programme structure, please visit https://www.swbio.ac.uk/programme/.

Funding for 2020/21
These studentships are available to UK and EU nationals who have established UK residency (EU nationals must have ordinarily lived in the UK throughout the three years preceding the start of the studentship).

The four core universities (Bath, Bristol, Cardiff and Exeter) have a very limited number of fully-funded four year studentships for EU students who do not meet the residency requirements (1-2 studentships per university)*. Please contact the relevant university for more information.

*These are not available for CASE DTP studentships or Standard DTP studentships with a collaborative partner

Project Description
Antimicrobial resistance (AMR) is one of the greatest threats to human health of our time causing a predicted 10
million deaths per year by 2050 with a total cost of $100 trillion by the same date. The most important resistance
mechanisms are carried on plasmids, which are mobile DNA elements that can spread by horizontal gene transfer within bacterial populations. Data generated in Gaze’s lab shows that mobile resistance mechanisms are selected for by very low concentrations of antibiotics, suggesting that selection for AMR occurs within polluted natural environments, within the human and animal microbiomes as well as within individuals taking antibiotics. Novel resistance mechanisms regularly emerge in clinical pathogens threatening to make even our antibiotics of last resort ineffective. Discovering ways to prevent or even reverse the spread of AMR would be truly ground breaking.

This project “CRISPR-Cas9 gene drives to eradicate antimicrobial resistance from bacterial communities” will
develop a recently discovered bacterial immune system called CRISPR-Cas to target and destroy mobile bacterial resistance plasmids. The project integrates synthetic biology, experimental evolution and mathematical
modelling to predict and test (1) the effectiveness and (2) the consequences of CRISPR-Cas9-mediated AMR removal in a soil microbial community. The Van Houte lab has a collection of conjugative elements and bacteriophages that will be tested as delivery vehicles to mobilize CRISPR-Cas9 and has experience with culturing soil microbial communities in a realistic environment - sterilized compost.

First, the student will use mathematical modelling to generate predictions when mobile CRISPR-Cas9 can remove AMR genes from bacterial populations. The student will test these predictions by examining the effectiveness of CRISPR-Cas9 delivery vehicles to target plasmid-encoded AMR genes in a microbial community. Techniques that will be used are a.o. fluorescence microscopy and q(RT-)PCR.
Finally, the student will study the consequences of AMR targeting by mobile CRISPR-Cas9 (e.g. evolution of
resistance to CRISPR-Cas9, shifts in community composition), using cutting-edge techniques to study hostplasmid associations and various sequencing approaches.

The integration of CRISPR-Cas and AMR research is highly novel and is supported by established research
programmes on CRISPR-Cas and AMR in the Van Houte and Gaze laboratories in the Environment and Sustainability Institute at the University of Exeter. Expertise in mathematical modelling expertise by Ben Ashby at the University of Bath. The student will receive training in synthetic biology, experimental evolution, molecular microbiology, genetics and modelling.

Eligibility
To be eligible for a fully-funded studentship, you must meet both the academic and residence criteria in line with UKRI guidelines. Please see the following webpage for further details https://www.swbio.ac.uk/programme/eligibility/.

A fully-funded four year SWBio DTP studentship will cover:

• a stipend* at the standard UKRI rate; currently £15,009 per annum for 2019-2020
• research and training costs
• tuition fees (at the standard UKRI rate)
• additional funds to support fieldwork, conferences and a 3-month internship

Funding Notes

SWBio DTP funded studentship available for September 2020 entry. The studentship will provide funding of fees and a stipend which is currently £15,009 per annum for 2019-20, on a full time basis.

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