Non-invasive radiation biodosimetry through metabolomics

该项目将结合我们的代谢组学和应激信号专业知识与Sionex公司的传感器芯片专业知识，开发使用代谢标志物快速无创评估辐射暴露和损伤的仪器，从而解决该联盟的总体主题。体内辐照触发了许多参与细胞间信号传导的基因的表达，这些基因的蛋白质可以对细胞代谢产生广泛的影响。我们从现代代谢组学方法获得的初步数据表明，这些变化反映在尿液和痰中代谢物谱的变化中。这种代谢组学分析提供了几个关键优势，包括简单，无创收集，因此具有非常高通量生物剂量计筛选的潜力。我们还将研究使用a的可能性

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.