Grant: Project Grant

Innate immunity is an ancient system of host defense that predates the adaptive immune system and is conserved in almost all multicellular organisms from insects to mammals. Innate immunity relies on a set of protein receptors that are strategically expressed in cells that are likely to encounter pathogens such as bacteria and viruses, early on in an infection. The interaction of these receptors with components from the pathogen, propagates a signal into the cell that leads to changes in gene expression and accompanying responses by the host that work to eliminate the pathogen. Pathogens try to counteract immunity to gain an advantage by for example injecting toxic proteins into the host. It is necessary to understand the molecular of both of these processes to help develop better therapeutics against infection. This research proposal aims to elucidate the atomic level details for host-pathogen interactions on both sides of interface: 1) IFIT host defence proteins that fend of viral infection and 2) Bacterial effector proteins called YopJ acetyltransferases, which are enzymes that bacteria deliver into the host to subvert the immune response. Understanding the molecular details of how these proteins engage their respective target molecules to enhance or undermine the immune response is an important step towards the development of therapeutic drugs in diseases like cancer and autoimmune disorders, as well as several infectious and inflammatory diseases.