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Systems analysis of the cardiac hypoxia response in Drosophila
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Drosophila is an emerging model for studying genetic influences on heart function, and has also been found to be highly tolerant to hypoxia. We adopted a systems biology approach to discover important hypoxia-tolerance strategies in ATP-generating metabolism in Drosophila heart. This work describes the design of automation technology for rapidly screening the in vivo cardiac hypoxia response in adult flies, the use of NMR metabolomics to gather global metabolic profiles, and the integration of these data into a genome-wide reconstruction of central metabolism. The model was further refined with gene expression data and used with specific metabolomic datasets to study the effects of age on the hypoxia response, and then to study a strain of flies that had been experimentally selected to survive chronic hypoxia. The dissertation offers clues to hypoxia tolerance in flies, generating hypotheses for further research, and also provides a technology platform for a systematic perturbation analysis.
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