2026-27 Project (Dyson & Mostowy & Knight)
PHACTS: Unravelling PHAge-baCTeria-host immune dynamicS to inform phage therapy
SUPERVISORY TEAM
Supervisor
Dr Zoe Dyson at LSHTM
Faculty of Infectious & Tropical Diseases, Department of Infection Biology
Email: zoe.dyson@lshtm.ac.uk
Co-Supervisor
Professor Serge Mostowy at LSHTM
Faculty of Infectious & Tropical Diseases, Department of Infection Biology
Email: serge.mostowy@lshtm.ac.uk
Co-Supervisor
Professor Gwen Knight at LSHTM
Faculty of Epidemiology & Population Health, Department of Infectious Disease Epidemiology and Dynamics
Email: gwen.knight@lshtm.ac.uk
PROJECT SUMMARY
Project Summary
Phage therapy, the clinical application of phages to control bacterial infections, has enormous potential to combat the silent pandemic of antimicrobial resistance (AMR). However, progress on this important treatment option has been hampered by a lack of fundamental understanding of the interactions leading to complex dynamics in different growth conditions and in the presence of an immune system. By bringing together state-of-the-art interdisciplinary techniques and expertise in microbiology, pathogen genomics/bioinformatics, clinical infection models, microcalorimetry, cellular microbiology, high content imaging, and mathematical modelling, we are uniquely placed to address these key knowledge gaps to accelerate the successful clinical application of phages for Staphylococcus aureus, Klebsiella pneumoniae and Shigella spp.
Project Key Words
antimicrobial resistance, mathematical modelling, phage therapy
MRC LID Themes
- Infectious Disease
- Global Health
- Health Data Science
- Translational and Implementation Research
Skills
MRC Core Skills
- Interdisciplinary skills
- Quantitative skills
- Whole organism physiology
Skills we expect a student to develop/acquire whilst pursuing this project:
- microbiology
- antimicrobial resistance
- bioinformatics
- mathematical modelling
Routes
Which route/s are available with this project?
- 1+4 = Yes
- +4 = Yes
Possible Master’s programme options identified by supervisory team for 1+4 applicants:
- LSHTM – MSc Medical Microbiology
Full-time/Part-time Study
Is this project available for full-time study? Yes
Is this project available for part-time study? Yes
Location & Travel
Students funded through MRC LID are expected to work on site at their primary institution. At a minimum, all students must meet the institutional research degree regulations and expectations about onsite working and under this scheme they may be expected to work onsite (in-person) more frequently. Students may also be required to travel for conferences (up to 3 over the duration of the studentship), and for any required training for research degree study and training. Other travel expectations and opportunities highlighted by the supervisory team are noted below.
Day-to-day work (primary location) for the duration of this research degree project will be at: LSHTM – Bloomsbury, London
Travel requirements for this project: None
Eligibility/Requirements
Particular prior educational requirements for a student undertaking this project
- Minimum standard institutional eligibility criteria for doctoral study at LSHTM
Other useful information
- Potential Industrial CASE (iCASE) conversion? = No
PROJECT IN MORE DETAIL
Scientific description of this research project
Vision:
Antimicrobial resistance (AMR), the process by which infectious bacteria become resistant to antibiotics used to control them, is an urgent global health threat. The cost of inaction is estimated to be $100 trillion USD and 10 million deaths by 2050. Among AMR bacterial pathogens, the ESKAPE pathogens, a group of six bacteria including Staphylococcus aureus and Klebsiella pneumoniae (the ‘S’ and ‘K’), driving the majority of hospital acquired infections and WHO priority pathogens such as Shigella are of particular concern. Bacteriophages (phages) are naturally occurring viruses infective for bacteria. Phages and bacteria have been locked in a co-evolutionary arms race and predator-prey relationship as long as they have existed. Phages kill their bacterial hosts at the end of an infection cycle, releasing progeny phages that repeat this process, making them an appealing means of controlling infectious bacteria.
Given the global health threat posed by AMR bacterial pathogens, there is renewed interest in alternative treatment options, including the use of phages in clinical practice, termed ‘phage therapy’. Sporadic compassionate use case studies have demonstrated that phage therapy can resolve otherwise untreatable AMR infections, however, the failure of several clinical trials has emphasised that many knowledge-gaps remain which have hampered progress towards routine phage therapy. These include details of (i) the dynamics of phage-bacteria interactions in the presence of human components, required to optimise dosages and determine fundamental drivers of successful phage cocktail therapy, and (ii) rates and mechanisms of phage resistance. PHACTS will bring together researchers from a variety of disciplines to address these knowledge gaps.
Approach and aims:
PHACTS will focus on fundamental biological interactions to improve our ability to understand one of the most ancient evolutionary interactions and generate criteria to optimise phage therapy. PHACTS unites distinct but highly complementary expertise in (i) cellular microbiology, in vivo infection models, high resolution microscopy techniques (Serge Mostowy), (ii) pathogen genomics, evolutionary biology, bioinformatics (Zoe Dyson), and (iii) mathematical modelling of microbiological interactions (Gwen Knight). Using a combination of in silico, in vitro and in vivo experimental analyses, PHACTS will improve (i) our understanding of phage-bacteria interactions and (ii) use this understanding to generalise predictive therapeutic benefit. PHACTS will provide a stepwise change in biology as well as underlying evidence to inform strategies for successful phage therapy for S. aureus, K. pneumoniae, and Shigella spp.
Objectives:
- Characterise phage-bacteria dynamics in vitro
- Explore phage-bacteria interactions in vivo using zebrafish infection models
- Generalize, support and extend in vitro and in vivo experimental work using mathematical modelling
Techniques:
- Microbiology, cell biology, and host response using infection of tissue culture cells and zebrafish infection models
- Whole genome sequencing and bioinformatic analysis of phages and bacteria to understand the evolutionary relationships between phages, bacteria, and antimicrobial resistance. This work will also focus on the spread of bacteria within hospital settings
- Data analysis and model fitting to determine parametric distributions for resistance diversity in different settings
- Evolutionary mathematical models fit to existing and newly generated data from resistance transfer experiments
- Develop transfer assays to explore stability and resistance diversity levels under different competition assays
- Dynamic transmission models to explore bacterial transmission within hospital settings fit to data on within host populations
Further reading
Relevant preprints and/or open access articles:
(DOI = Digital Object Identifier)
Other pre-application materials: None
Additional information from the supervisory team
The supervisory team has provided a recording for prospective applicants who are interested in their project. This recording should be watched before any discussions begin with the supervisory team.
Dyson & Mostowy & Knight Recording
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