Phage therapy, the use of viruses that only infect bacterial cells and kill them, is a promising potential solution to the antimicrobial resistance crisis that is threatening modern medicine1. To avoid resistance evolution against phages and to maximize the antimicrobial effect, phages are often used in combination with antibiotics. Such combination treatments can show more effective bacterial killing than either treatment alone, which is called phage-antibiotic-synergy. Sublethal antibiotic levels can for example increase phage production by delaying lysis of bacterial host cells2. Yet, the mechanisms that determine the synergy between antibiotic effect and phage lysis of bacterial cells remain poorly understood and hinder effective design of phage-antibiotic combination treatments.
This project will combine synthetic engineering, bioimaging, experimental infection assays and computational modelling to understand and predict the efficacy of killing the priority pathogen Pseudomonas aeruginosa depending on the antibiotic class and the phage lysis system3. We will use synthetic phage lysis systems as well as natural phages to quantify the impact of different antibiotics on lysis efficacy through changes in bacterial physiology. Mathematical modelling will be used to understand experimental observations and to predict optimal phage-antibiotic treatments. Combining synthetic and natural systems with modelling will allow us to study the intracellular mechanisms of phage-antibiotic synergy and link them to the population dynamics of bacterial killing.
This project provides a unique opportunity to obtain training in a wide range of interdisciplinary skills, including experimental microbiology, synthetic engineering techniques, bioimaging and infectious disease modelling. We are looking for a student who is either coming from a biological background with a keen interest in learning mathematical modelling or from a mathematical / physics / computer science background with a genuine interest in doing microbiology experiments. Microbiology and molecular wet lab skills or infectious disease modelling skills are beneficial but not required.
Training
This project will provide multidisciplinary training in synthetic engineering (e.g. molecular cloning), experimental microbiology (e.g. phage handling), bioimaging techniques (e.g. single cell microscopy), ecology and evolution (e.g. phage-bacteria population dynamics) and mathematical modelling (e.g. writing differential equation models in R or Python). The student will gain a broad skillset highly relevant to industry/academia (including laboratory techniques, data analysis and mathematical modelling tools) and will be integrated into MERMan, the UK’s largest cluster of microbial evolution research groups, providing a supportive and stimulating research environment.
Eligibility
Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in microbiology, biophysics, mathematics or computer science. Candidates with experience in microbiological lab skills or infectious disease modelling skills with a keen interest in interdisciplinary work are encouraged to apply.
Before you Apply
Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.
How to Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit https://www.bmh.manchester.ac.uk/study/research/international-phd/
Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team FBMH.doctoralacademy.admissions@manchester.ac.uk
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/
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