Using Phage Therapy to Combat Antibiotics Resistant Pseudomonas Aeruginosa Infections - Biosciences, PhD (GW4 BioMed MRC DTP)

About
Supervisory Team: Dr Edze Westra
Location: Cornwall, Penryn Campus

Project
Pseudomonas aeruginosa is an opportunistic human pathogen, which infects immunocompromised patients, is often resistant to antibiotics, and has been identified by the WHO as a top priority pathogen. European phase I-II clinical trials are currently ongoing to test whether viral predators of bacteria (phages) can be used as an alternative to antibiotics to treat burn wounds of patients infected with Pseusomonas aeruginosa [PhagoBurn], and similar approaches may be used in the future to treat lung infections of cystic fibrosis patients.

A potential issue of this approach is that bacteria can rapidly evolve phage resistance, which can lead to problems similar to those associated with antibiotics. Bacteria possess a range of defence mechanisms to combat phage infection (van Houte, Buckling and Westra, MMBR 2016), and it is known that these different mechanisms differ with regards to their consequences for bacterial fitness (Westra et al. Curr Biol 2015) and phage persistence (van Houte et al. Nature 2016). However, our understanding of P. aeruginosa-phage interactions in clinical settings is limited by the fact that these experimental analyses have so far only been performed using laboratory growth media and monoclonal bacterial populations.

This project aims to understand how P. aeruginosa-phage interactions take place in more clinically realistic environments. We will use mathematical modelling and experimental analyses to examine how the presence of other human pathogens (Staphylococcus aureus, Acinetobacter baumannii and Burkholderia cepacia), which often co-infect with P. aeruginosa, impacts the selection for bacterial defense mechanisms and their consequences for P. aeruginosa fitness and virulence, as well as phage persistence and infectivity. Furthermore, the project will examine the effect of environmental complexity by using sputum media, which mimics the cystic fibrosis lung environment. Results obtained in vitro will be tested in vivo using a C. elegans infection model, and a limited number of tests can be done using a mouse lung infection model system developed by Prof. Winstanley, a collaborator on this project (University of Liverpool). The student will be actively involved in these animal experiments, and will follow the appropriate training courses.

The student will receive further training in mathematical modelling, experimental evolution, molecular microbiology, and genetics. This interdisciplinary project integrates research on bacterial defence mechanisms (Westra, Exeter), mathematics (Ashby, Bath), invertebrate infection models (Viney, Bristol and Buckling, Exeter) and bacteria-phage co-evolution in a community context (Buckling, Exeter). The aims of this research are highly novel and supported by established research programmes on P. aeruginosa virulence and phage defences in Westra’s and Buckling’s lab in the Environment and Sustainability Institute at the University of Exeter. Ben Ashby at Bath will provide expertise and training in mathematical modelling. This work will bridge the gap between in vitro and in vivo work and contribute to the development of a novel technology to combat P. aeruginosa infections.

During this interdisciplinary project the student will be exposed to a wide range of methods and expertises. The student will participate in international conferences and meetings to broadly disseminate the results of this project, and data will be published in peer-reviewed journals.

Start date: October 2018

Most studentships will be 3.5 years full time or up to 7 years part-time, and can be longer where additional training is undertaken.


How to apply
APPLICATIONS OPEN ON 25 SEPTEMBER AND CLOSE AT 17:00 ON 24 NOVEMBER 2017.

IMPORTANT: In order to apply for this project, you should apply using the DTP’s online application form. More information on the application process may be found here: http://www.gw4biomed.ac.uk/projects-2/for-students/

You do NOT need to apply to the University of Exeter at this stage – only those applicants who are successful in obtaining an offer of funding from the DTP will be required to submit an application to study at Exeter.