Genome-guided personalised phage therapy

The global antimicrobial resistance crisis is predicted to result in 10 million yearly deaths by 2050 and has re-galvanised interest in the use of bacteriophage as treatments for antibiotic-resistant bacterial infections. Bacteriophage (or phage) are viruses that can infect and kill bacterial cells. Phages are highly specific: each can infect and kill only a subset of strains within a bacterial species, dependent on the expression of specific receptor molecule(s) on the bacterial cell. This means phage can be used to kill an infecting bacterium while leaving the broader host microbiota intact, reducing the risks of collateral resistance evolution and other negative side-effects. However, the very nature of their specificity presents a limitation for phage application at scale, due to the time and resources required to identify and validate suitable phages on a patient-by-patient basis, which delays the onset of treatment. In this project, you will use genomic analyses with/without laboratory experimentation to develop new approaches to ‘match’ phage to individual bacterial strains. You will focus on Enterobacter cloacae, a World Health Organization priority antimicrobial resistant bacteria and major cause of hospital-associated infections globally. You will identify the specific receptor molecule variants targeted by a set of anti-Enterobacter phage, and develop novel genomic approaches to predict phage susceptibility from a bacterial genome sequence. Outcomes for you as a student: • Experience in large scale genomic sequence analysis including bioinformatic workflows and high-performance computing, representing key skills in the modern microbiology research tool-box • Laboratory experience, including bacterial and phage culture, phage susceptibility testing, DNA extraction and sequencing (optional) • Contribution to new approaches that will transform personalised phage therapy in Australia and beyond Resources you will be supported by: • World-leading bacterial genomics and phage research teams • Access to a unique bacterial strain collection and phage library • State-of-the-art microbiology laboratories • Remote-access, high-performance compute cluster What you will bring: • A passion for microbiology research to reduce the global burden of antimicrobial resistance • A background in biology, including microbiology and/or molecular biology • An interest in learning genomic analyses, including command-line computing i.e. telling the computer what to do by typing a series of words rather than using a mouse to point and click. You don’t need prior experience in this, just a keen interest and demonstrated capacity to learn! The project can be tailored to suit individual research interests and degree levels e.g. to optionally include experimental lab work as well as genomic analyses.