Determining the regulatory control of prokaryotic antiviral defence systems

The spread of antimicrobial resistance is a slow-moving pandemic that has been identified by the WHO as one of the top 10 threats facing humanity. It has been estimated that in 2050 approximately 10 million people will die each year as a result of antimicrobial resistance. Bacterial immune systems are key determinants of the spread of antimicrobial resistance. Moreover, they can

severely hamper the efficacy of therapeutic application of phages in clinical settings, which is considered a viable alternative to conventional antibiotics to treat infections with resistant pathogens. For these reasons it is critical to identify bacterial defence systems and to understand how they operate. Recent work has revealed that

bacteria carry many more defences than previously thought, and we are only just beginning to understand how they work. In this project, the student will study the interplay between a novel innate defence system that was identified in our lab (MADS) and the CRISPR-Cas adaptive immune system of the important opportunistic

pathogen Pseudomonas aeruginosa. This WHO priority pathogen is one of the leading causes of hospital acquired infections and a major cause of lung infections in cystic fibrosis patients. Because of its high levels of antimicrobial resistance, phage therapy is in some cases already being used to treat patients.