Characterising the genetic determinants of phage infection in mycobacteria

Viruses that infect bacteria, known as bacteriophages, have long been important in helping us to understand key aspects of bacterial physiology. More recently, the systems the bacteria use to fight back, such as Crispr/Cas9 have lead to an explosion in interest in how viruses infect bacteria and how the bacteria respond to these infections. Exploring these relationships has the potential to uncover new therapeutics, new molecular biology tools, and help us to understand the evolutionary history of these organisms. In this project the student will take advantage of our ordered, single-gene deletion library for Mycobacterium bovis BCG which is the vaccine strain for Mycobacterium tuberculosis. The student will use our established systems biology robotics and platforms to explore the genome-wide requirements for phage infection by isolating strains that become either hyper-resistant, or hyper-susceptible to phage infection. The student will then use cutting-edge molecular microbiology tools, biochemistry and structural to understand the molecular mechanisms that lead to these changes. For example, we recently identified a novel family of enzymes found in mycobacteriophage that enable cleavage of the core of the bacterial cell wall for the first time(1). This project will lead to a better understanding of mycobacterial physiology and ultimately to the development of new tools for treating mycobacterial infections.