Mechanisms and evolution of innate immune signalling activation across species

Host species vary markedly in their susceptibility to infection (e.g. for COVID-19, malaria, or tuberculosis). Variability in disease outcome is driven by differential induction of the immune system, especially for inflammatory diseases like COVID-19. This process depends on adaptive immunity, but also critically innate immunity: a conserved defence system built of recognition, signalling, and effector molecules. Immune genes evolve especially rapidly compared to the rest of the genome. However, little is known how immune evolution affects gene expression across species: we have yet to tie immune evolution to observable differences in the induced response. My research shows closely-related species can differ markedly in their induced immune response. Using a comparative approach, I will systematically characterise immune induction patterns of diverse species. Differences should rely on either i) alternate organisation of conserved immune pathways, or ii) gene duplications that evolve to promote novel pathway connections. Assessing gene expression, molecular evolution, and signalling organisation will reveal how these variables produce differences in immune activation. Ultimately, I will tie immune evolution to differences in the induced immune response. This proposal will greatly improve our ability to predict interactions between pathogens and novel host species, and to understand factors affecting the innate inflammatory response.