Phages and their ecological strategies to advance phage therapy

We are running out of antibiotics to treat bacterial infections. One solution is to use a mixture of bacteriophages (phages), naturally occurring bacterial viruses that leave human cells unharmed. With thousands of phages in existence, identifying those with effective properties is a stumbling block. We need to understand which phage combinations have the right properties to kill pathogenic bacteria. Identifying useful phages is limited by diverse novel genomes, oversimplistic selection criteria and a lack of understanding of phage ecology. To address this, this project will carry out extensive tests establishing the genetic basis of phage behaviours that determine good clinical outcome. There are currently no frameworks to correlate phage traits with therapeutic potential. To address this, the student will use our biological resources and the models we have developed to fully assess the biology of phages that target E. coli and Klebsiella pneumoniae. Full genomic and extensive phenotypic data will be collected for the different phages to identify key proteins that will be investigated at a mechanistic level. Transcriptional, proteomic and metabolomic profiling will be used to map these traits to ecological frameworks. From this, we will identify novel traits associated with beneficial phages, and be able to determine their mechanistic basis. This will allow us to design and extensively test ecologically informed therapeutic cocktails and transform phage therapy development.