Innate Immune Regulation in Viral Infection and Cancer Chemotherapy (360G-Wellcome-325794_Z_25_Z)

Our goal is to understand how we defend ourselves from infection through activation of inflammatory innate immune pathways, how these defensive processes work, and how viruses evolve to escape them. We will compare non- pandemic viruses e.g. MERS-CoV with pandemic relatives e.g. SARS-CoV-2 to understand how host responses differ and how this links to viral genetics and protein expression. Such studies will reveal what is special about pandemic viruses and help us understand how to risk assess the pandemic potential of emerging viruses. We will also study the molecular details of how innate immunity is manipulated by viruses, focusing on epigenetic control of defensive gene expression by coronavirus nucleocapsids and lentiviral accessory proteins. We will focus on viral manipulation of epigenetic regulators by infection including PAF1c, HUSH and HUSH2. Finally, we will apply our understanding of innate immunity to understand how anthracycline chemotherapeutics activate interferon production by targeting mitochondria with a view to understanding novel mechanisms relevant to infection and cancer and also producing new inhibitors with novel properties. We expect the new knowledge we generate to be relevant to both sterile inflammation and infection and to provide opportunity for therapeutic intervention relevant to the many human diseases exacerbated by inflammation.