Influenza A Virus (IAV) – or more simply “flu” – is the primary infectious agent that causes our seasonal flu outbreaks and can lead to pandemic level health emergencies due to seasonal strain changes and lack of population immunity to them. Though advances have been made over decades to supply health care systems with vaccines, very few new disease treatments or preventions have been established. My project focuses on a new experimental approach whereby we have developed a specialized immune cell from stem cells – specifically adapted to function in the lungs – that inactivates respiratory viruses in viral lung infections and reduces viral lung disease in animal experiments. For this project, I am seeking to test the ability of this special stem cell-derived immune cell to inactive the flu virus and reduce respiratory disease in experimental animals infected with flu (IAV). I plan to test and compare how these cells inactivate different strains of flu. By researching these cells in experimental animals and then translating our knowledge of them to the human immune cell counterpart we will be able to understand the mechanisms by which these cells inactivate respiratory viruses. This information can be used to modify the cells to create viral therapeutics that reduce respiratory viral diseases in humans, including the virus that causes COVID, and lower the burden on health care systems. This project will establish the research platform from which I will broaden its application during my future career development.

Bacteria are becoming increasingly resistant to antibiotics, leading to 1.27 million deaths worldwide this year. There is an urgent need to develop effective new treatments for these infections. Bacteriophages, small viruses that are natural predators of bacteria, provide an attractive alternative for therapeutic use. However, as bacteria encode many defence systems to protect them from phage infection, a more thorough understanding of phage-bacteria dynamics is required before they can be effectively deployed. My work will focus on Pseudomonas aeruginosa, a notoriously difficult to treat human pathogen. I will create a comprehensive library of all anti-phage defence systems in P. aeruginosa, and these systems will be monitored for changes in expression in the presence of bacterial signaling molecules. This will establish whether bacteria communicate to warn each other of impending phage infection, and if those signals drive expression of anti-phage defence systems. This is the first comprehensive study to examine how bacteria respond to phage infection and ultimately protect themselves. The knowledge gained in this study will allow us to develop highly effective phage therapy treatments.