Bacterial pathogens have developed various molecular mechanisms to subvert macrophage cell death pathways during infection. We have recently identified that apoptosis-inducing compounds eliminate intracellular Legionella infections. This raises the prospect of targeting pathogens with host-directed drugs.
We now aim to
- identify the mechanism by which pathogens interfere with host cell death signalling pathways.
- discover how apoptosis eliminates bacterial infections.
For this, we use CRISPR whole genome library screens to generate mutant macrophages that fail to eliminate intracellular pathogens. Identified genes will be further validated in established infections models using live-cell imaging, as well as immunological and biochemical approaches.
This will be performed as part of the NHMRC Program Grant on Cellular Microbiology, in collaboration with members of the Host-Pathogen Molecular Biology Unit (Monash), James Vince (WEHI), Gordon Dougan (Sanger UK), and Monash Micro Imaging