Exploring phage therapy against intracellular pathogens using the in vivo zebrafish model
Secondary Supervisor(s): Dr Antonia Sagona
University of Registration: University of Warwick
BBSRC Research Themes:
Project Outline
Intracellular bacterial pathogens pose a significant challenge as they can persist within host cells and evade immune defences. Treating these infections often requires prolonged antibiotic use, which can be ineffective due to low intracellular drug accumulation and may drive the emergence of antimicrobial resistance (AMR). AMR is a growing global concern and tackling it is a key priority in the UK National Action Plan.
Phage therapy is a promising alternative to antibiotics, but how phages act against intracellular pathogens remains largely unexplored. This project offers an exciting opportunity to work at the cutting edge of microbiology, immunology and host-pathogen research. Using the in vivo zebrafish embryo model, you will investigate phage-pathogen-host interactions in real time, gaining mechanistic insight into the therapeutic potential of phages against hard-to-treat intracellular infections.
This project aims to discover and characterise novel bacteriophages targeting intracellular pathogens, with a focus on understanding their mechanism of action and potential therapeutic activity in vivo.
The primary objectives include:
1. Isolate bacteriophages that effectively target intracellular pathogens (eg. Pseudomonas aeruginosa, Staphylococcus aureus, Burkholderia cenocepacia);
2. Perform phage whole-genome sequencing and bioinformatic analysis to characterise the newly identified phages;
3. Perform zebrafish embryo infection assays to understand phage activity in vivo;
4. Use high-resolution and high-throughput microscopy to visualise phage-pathogen-host interactions at cellular resolution;
5. Analyse host immune responses during phage therapy to determine host-modulating effects.
This interdisciplinary project will equip the student with a broad skillset in microbiology, molecular biology, genomics, imaging, and in vivo modelling - ideal for those interested in infection biology, AMR, and the development of next-generation antimicrobial strategies.