Center for High-Throughput Minimally-Invasive Radiation Biodosimetry

项目概述：该CMCR的首要主题是超高通量生物剂量学。众所周知，这是对大规模放射性事件作出任何有效反应的核心和必要组成部分。在这个CMCR项目存在的4年多的时间里，我们已经实现了每天6000个样品的生物剂量测定样品吞吐量，并在2010年实现了每天30,000个样品的目标。目前可用的标准生物剂量测定方法的通量通常小于100个/天。首次证明了单基因组在暴露后的一段重要时间内预测辐射剂量的能力，而无需单独的暴露前控制。证明了基于尿液的代谢组学生物剂量测定系统的潜力，信号以剂量-反应方式增加，信号寿命至少为几天。我们最初的应用只专注于外部全身光子照射。这项更新应用的主要主题之一是评估可能发生的各种其他辐射情景的重要性，特别是部分体照射、内部发射器、低剂量率和中子照射的影响。由于我们已经开发了高通量系统，用于使用各种生物标志物进行生物剂量测定，我们现在处于一个独特的位置，可以探索这些生物标志物在预测急性辐射综合征的个体间敏感性方面的应用。我们有两个相互交织的动机；首先是研究高通量生物标志物与个体急性辐射敏感性之间的相关性，其次是探索相关机制。这两种方法都建立在我们迄今为止所完成的高通量生物剂量测定工作的基础上，没有这些工作是不可能实现的。

DESCRIPTION (provided by applicant): PROJECT SUMMARY: The overriding theme of this CMCR is ultra high-throughput biodosimetry. It is well established that this is a central and necessary component of any effective response to a large scale radiological-event. In the 4+ years that this CMCR program has been in existence, we have Achieved a biodosimetry sample throughput of 6,000 samples per day, and are on target for 30,000 samples per day in 2010. Throughputs with currently available standard biodosimetry approaches are typically <100/day. Demonstrated, for the first time, the ability of a single gene set to predict radiation dose, throughout a significant window of time post exposure, without the need for individual pre-exposure controls. Demonstrated the potential for a urine-based metabolomics biodosimetry system, with signals increasing in a dose-response manner, and with a signal lifetime of at least several days. Our initial application focused exclusively on external whole-body photon irradiation. One of the main themes of this renewal application is to assess the significance of the variety of other radiation scenarios that are likely to occur, in particular the effects of partial-body exposure, internal emitters, low dose rate, and neutron exposure. In that we have developed high-throughput systems for using various biomarkers for biodosimetry, we are now in a unique position to probe the application of these biomarkers for predicting inter-individual sensitivity to acute radiation syndromes. We have two interlaced motivations here; The first is to investigate correlations between our high-throughput biomarkers and individual acute radiation sensitivity, and the second is to probe the associated mechanisms. Both of these approaches build on - and would not be possible without - the high-throughput biodosimetry work that we have accomplished to date.