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Ultra-High-Throughput Directed Evolution of Antimicrobials using Droplet Microfluidics. PhD in Physics and Astronomy (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 Fabrice Gielen, Department of Physics and Astronomy, College of Engineering, Maths and Physics, University of Exeter

Additional Supervisors
- Dr Stineke van Houte, Department of Biosciences, College of Life and Environmental Sciences, University of Exeter
- Professor Mike Allen, Plymouth Marine Laboratory
- Prof Yves Briers, University of Ghent, Belgium

Location: University of Exeter, Streatham Campus, Exeter, EX4 4QJ

Programme Overview
The South West Biosciences Doctoral Training Partnership (SWBio DTP) 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 has evolved into a major healthcare threat which is further exacerbated by the diminished number of antibiotics in development. Alternatives to antibiotics such as phages and phage endolysins (their lytic enzymes) are being actively researched. This PhD project aims at understanding sequence-function relationships for endolysin activity and unravel the rules for successful bacteriolysis. developing novel high-throughput assays for the directed evolution of bacteriophage endolysins, enzymes capable of killing host bacteria from outside.

In this project, we will combine cutting-edge high-throughput screening technologies in microfluidic droplets with protein engineering to create an endolysin evolution platform. Microdroplet technology has already shown enormous potential for enzyme evolution and the exploration of sequence space at high-throughput and low cost. Each droplet, whose volume typically ranges from femto to nanoliter scale represents a single reaction in which individual enzymes are confined. By encapsulating a single gene corresponding to a single enzyme variant, large gene libraries can be screened in a time and resource efficient manner. FG’s group is developing label-free technology platforms for the high-throughput analysis of bacteria-phage interactions and this project builds on this high-profile work [1]. During this studentship, you will be developing/furthering skills across many fields from microfluidic fabrication, building and operation of complex optical setups, protein engineering, biophysics, gene expression and microbiology.

In summary, this is an experimental project to develop novel high-throughput functional assays that can identify novel bacteriolytic enzymes. You will be based in the newly-built Living Systems Institute which brings together scientists from different disciplines and host cutting-edge equipment. This PhD studentship will also allow you to take advantage of the expertise available in Physics, Biosciences, the Environment and Sustainability Institute at Exeter and Plymouth Marine Laboratory to shine new light on endolysin evolution. The supervision team is composed of Dr. Fabrice Gielen (Living Systems Institute, Exeter), Dr. Stineke van Houte (Environment and Sustainability Institute, Penryn) and Prof. Mike Allen (Plymouth Marine Laboratory) who have complementary expertise on the subject.

[1] Gielen et al. PNAS (2016).

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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