Connecting causes and immune consequences of infection-induced metabolic change (360G-Wellcome-207467_Z_17_Z)

This research proposal focuses on metabolic changes driven by the immune response to bacterial infection in the model system Drosophila melanogaster. We will use in vivo genetic manipulations, experimental and computational analysis of gene expression, and experimental metabolomics to address two overarching biological questions. First, how does immune activation drive metabolic change? Second, how do these metabolic changes aid or impede the realised immune response and host survival? The proposal contains three aims directed at these questions. In the first aim, we use whole-animal metabolomics to identify metabolite level changes driven by different infections. In the second aim, we identify signals and transcriptional regulators responsible for the concerted regulation of metabolic enzymes during infection, and connect these signals and regulators with their downstream immunometabolic consequences. In the third aim, we target specific metabolites for analysis, using in vivo genetics to determine which immune- driven metabolic changes have important effects on realised immunity and tolerance of infection. Key goals: we will • identify the metabolite changes resulting from different bacterial infections • establish how these changes are driven by innate immune detection and signalling • connect specific metabolite changes with their effects on infection tolerance and immune function in vivo.