Discovering human host defence mechanisms at the Toxoplasma gondii vacuole

Toxoplasma gondii is the most prevalent human parasitic infection on the planet, causing disease in people with compromised immune systems. Normal individuals control the infection, but we do not understand how. The parasite forms a vacuole inside cells to hide from the immune system. A signalling molecule, gamma interferon, activates various pathways in different cells to control Toxoplasma. We will compare these pathways in two cell types Toxoplasma likes to infect, human endothelial cells and macrophages, to study mechanisms of control. We have developed an artificial intelligence software for detailed classification of anti-Toxoplasma effects in these cells. Human proteins central to anti-Toxoplasma control are ubiquitin-associated proteins. We will study these proteins on vacuoles to define how they control the parasite. To discover new pathways, we will use these proteins as bait to identify novel players in the vicinity. Our discoveries will help clarify human anti-Toxoplasma control and aid drug development.