Understanding the factors controlling phage lysis of bacterial cells

Rising antimicrobial resistance threatens global health and risks undermining modern healthcare. Phage therapy, using bacteria-specific viruses to treat bacterial infections, is a promising alternative to traditional antimicrobials. However, the development of effective phage therapy is limited by gaps in our fundamental understanding of phage biology. To exert their antimicrobial effect, phages must lyse the bacterial cell, yet phage lysis is very poorly understood in clinically-relevant systems. I will provide quantitative and predictive understanding of phage lysis of the priority pathogen Pseudomonas aeruginosa by answering the following research questions:

i) How do different phage lysis systems respond to changes in bacterial cell state?

ii) How do combinations of different lysis systems interact?

iii) Can phage-antibiotic synergy be predicted from the phage lysis system and antibiotic mode of action?

I will combine synthetic engineering and single-cell microscopy with biophysical and epidemiological modelling and phage infection experiments to provide multi-scale understanding of bacterial lysis. The results will advance fundamental phage biology and inform the design of effective phage therapy. Through this fellowship, I will develop new empirical and computational skills, obtain expertise in a new pathogen system, gain experience in independent project management and supervision, and develop into an internationally-recognised group leader.