Non-invasive radiation biodosimetry through metabolomics

通过代谢组学进行无创辐射生物剂量测定

• 批准号: 7052508
• 负责人: Albert J Fornace
• 金额: $ 75.7万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7052508
• 关键词: biological models; biological signal transduction; biomarker; biomedical equipment development; biotechnology; bioterrorism /chemical warfare; clinical research; cooperative study; functional /structural genomics; gene expression profiling; high throughput technology; human subject; laboratory mouse; liquid chromatography mass spectrometry; metabolomics; method development; miniature biomedical equipment; portable biomedical equipment; radiation dosage; sweat

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.

该项目将把我们的代谢组学和压力信号专业知识与 Sionex 公司的传感器芯片专业知识相结合，开发使用代谢标记物快速无创评估辐射暴露和损伤的仪器，从而解决联盟的总体主题。体内辐射会触发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。我们来自现代代谢组学方法的初步数据表明，这些变化反映在尿液和痰中代谢物谱的变化上。这种代谢组学分析具有几个关键优势，包括简单、非侵入性收集，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 汗液中的代谢组学特征，这将进一步提高吞吐量。基本支持研究将包括在小鼠模型系统中进行的表达谱和代谢物分析，以确定代谢组学中反映的组织和信号通路 变化。与信息学核心合作，将使用尖端信息学分析来选择彻底表征的代谢组学标记，以开发最佳的辐射代谢组学特征。转化研究将使用全身照射患者的样本将这些特征扩展到人类。代谢组辐射生物剂量测定实用产品的开发需要产品开发的四个阶段，包括发现、可行性、试验板研究和原型开发；这个项目涵盖了所有这些。总之，我们将与 Sionex 公司、产品开发核心和制造核心合作，以现有的最先进技术为基础，开发基于代谢组学的便携式高通量辐射生物剂量计，用于现场部署。连同辐射反应基因表达谱分析仪器的开发（项目 2），这些分析方法代表了高通量辐射生物剂量测定的补充方法。