The overall goal of the Systems Biology Core (Core B) is to provide experience, training and facilities for high-throughput measurements, together with expertise in bioinformatics and systems analysis in order to help the project investigators of the PPG to generate and test new hypotheses on systems-level mechanisms of short- and long-term hypoxia tolerance and susceptibility. Specifically, Core B will provide expertise and resources to: (a) acquire and analyze high-throughput data in humans, mice and flies on gene expression and genetic sequence variations in the context of hypoxia and the signaling pathways of interest; (b)acquire and analyze metabolic profiles and activity under normal and hypoxic conditions by NMR metabolomics, metabolic network reconstruction, and computational modeling;(c) to perform specific phenotypic measurements in flies and mice and develop computational models of physiological dynamics; and (d) deployment and curation of a physiological database and a web site and web-based tools for timely dissemination of data and findings. Core B will bring expertise in microarrays and pathway analysis, metabolic biochemistry and metabolomics, bioengineering and systems biology to work with all three projects and Core C in a variety of measurements and data analysis. In addition. Core B will be responsible for the web-based deployment and maintenance of data dissemination resources for the program project.
In the proposed PPG, the participating research projects will study adaptive mechanisms to hypoxia in cardiovascular and central nervous systems with the goal of identifying molecular signatures of hypoxia tolerance and susceptibility that will be relevant and useful clinically. The core will assist in these goals by providing systems biology tools and expertise to help the project to analyze gene expression, identify signaling pathways, determine molecular signatures and understand integrative mechanisms.
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