Chemistry for monitoring mitochondrial protein homeostasis

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Mitochondria are central to metabolism. They provide most of the ATP that drives cellular machinery. They are also hubs for redox signalling and key to programmed cell death. Consequently, mitochondrial dysregulation contributes to serious conditions. These include neurodegeneration, cancer and heart failure. Molecular probes developed in the Hartley group have helped show how mitochondrial reactive oxygen species (ROS) are generated, damage and signal within cells. In this project attention turns to mitochondrial protein biosynthesis and modification, which appear to underpin many mitochondrial diseases and the process of ageing. molecular probes will be developed to monitor mitochondrial protein biosynthesis and to determine the activity of enzymes and processes that modify proteins within the mitochondrial matrix. The project will involve modern synthetic chemistry, molecular probe and prodrug-type design, and chemical and biological validation of delivery. It will be underpinned by mechanistic organic chemistry combined with an understanding of physicochemical properties and mitochondrial biology. Overall, the research will provide a thorough training in organic chemistry and chemical biology.