This project will combine our metabolomics and stress-signaling expertise with the sensor-chip expertise of Sionex Corporation, to develop instrumentation for rapid non-invasive assessment of radiation exposure and injury using metabolic markers, thus addressing the overall theme of the Consortium. Irradiation in vivo triggers the expression of many genes involved in intercellular signaling, whose proteins can have wide-ranging effects on cellular metabolism. Our preliminary data from a modern metabolomics approach indicate that these changes are reflected in alterations in the spectrum of metabolites in urine and sputum. Such metabolomic analyses offer several key advantages including simple, non-invasive collection, and thus the potential for a very high-throughput biodosimeter screening. We will also investigate the potential for using a metabolomic signature in sweat, which would increase throughput still further. Basic supporting studies will include expression profiling and metabolite analyses carried out in mouse model systems, to determine the tissues and signaling pathways whch are reflected in metabolomics changes. Cutting-edge informatics analyses, in collaboration with the Informatics Core, will be used to select thoroughly characterized metabolomics markers to develop an optimal radiation metabolomics signature. Translational studies will extend these signatures into humans using samples from patients having total body irradiation. Development of a practical product for metabolomic radiation biodosimetry requires four phases of product development, encompassing discovery, feasibility, breadboard research, and prototype development; this project encompasses all of these. In summary, in concert with Sionex Corporation, the Product Development Core, and the Fabrication Core, we will build on existing state-of-the-art technology to develop a metabolomics-based portable high-throughput radiation biodosimeter, for deployment in the field. Together with the development of instrumentation for gene expression profiling of radiation response (Project 2), these profiling approaches represent complementary approaches for high-throughput radiation biodosimetry.
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