Tuning Immunity: Regulation and Functions of CaMKII at the Host-Pathogen Interface

Globalisation has enabled greater social and economic exchange, but also the rise and spread of infectious agents. Understanding how pathogens cause disease and how our immune system responds to infections is an increasingly urgent challenge for human health. Precise regulation of immune signalling events and the integration of multiple signal transduction cascades are critical in the rapid establishment of an effective immune response. While canonical pathways linking microbial detection to transcriptional responses are well characterised, the specific molecular signals that fine-tune inflammatory signalling remain poorly understood. I propose that the calcium-regulated kinase CaMKII modulates inflammatory sensing and boosts immunity against pathogens. Further, I propose that the CaMKII axis is an evolutionarily conserved target for diverse pathogens seeking to evade host immunity. With this work I will 1-Determine the dynamics of CaMKII activation and how CaMKII integrates with inflammatory signalling; 2-Define the immune regulatory functions of CaMKII signalling using animal models of infection; 3-Identify and characterise virulence factors from diverse pathogens that antagonise CaMKII to evade immune detection. This research plan at the interface between host and pathogen will reveal new mechanisms of immune sensing and pathogenesis. This will identify biological targets for novel antimicrobial and host-directed therapies.