Center for High-Throughput Minimally-Invasive Radiation Biodosimetry

该计划代表了一种以超高吞吐量的实际需求为动力的凝聚力方法 在各种不同的大规模暴露情况下的生物剂量学，以预测个人剂量和 个体对未来伤害的敏感性。我们的一个主要特征仍然是3种不同的高吞吐量 研究方法：全自动细胞遗传学(项目1)、基因表达(项目2)和代谢组学(项目2 3)。在吞吐量、到达结果的时间、剂量重建、 暴露情景识别和个体辐射敏感性预测，最终目标是量化其 在不同的大规模暴露场景中的最佳综合使用。这些项目有四个共同的主题： 1：《超越简单暴露》：迈向复杂暴露的高通量生物剂量学 IND将有各种各样的暴露情景，包括非常高的剂量率，中子暴露， 部分身体照射(全部来自最初的即时辐射)，以及不同的剂量率和低剂量率(从 外部辐射和内部暴露)。我们的目标是1)了解这些不同的暴露场景 调整我们开发的预测生物标记物的反应，并2)优化使用这些 生物标志物，用于识别/表征个人可能暴露于的这些不同的暴露情景。 2：《超越剂量》：迈向光子和中子的高通量个性化预报器- 诱导辐射敏感性与晚期辐射损伤：基因表达和代谢组学各有用处 用于预测晚期辐射引起的肺部疾病的个体化发病，以及预测哪种辐射 动物会死于这种疾病。这项工作将扩展到中子诱导的滞后效应，同时还 评估衰老细胞对晚期疾病发展和我们的肺部疾病特征的重要性。 3：“超越模型系统”：探索实验产生的光子和 活体人体暴露情景的中子生物标志物：目标是评估体内人类 暴露，但生物剂量分析开发通常是在体外照射的人身上进行的 血液或在动物体内。对于光子和中子，体外和体内产生的生物标记物将是 将对不同物种的生物标志物进行比较，并对其进行表征和比较。 4：优化生物标记物整合：三个不同的生物标记物系统反映了不同的平衡 能力，例如，吞吐量、到结果的时间、信号寿命、剂量重建、曝光 情景识别和个体放射敏感性预测。这里的目标是找出它们的最佳 在各种非常不同的可能的大规模暴露场景中的每一种情况下的综合使用。 三个科学核心(动物、辐射和剂量学以及生物统计学)汇聚了关键的支持 技术，每个核心支持每个研究项目。因为集成的本质是 研究表明，这在效率上有很大的提高。

This Program represents a cohesive approach motivated by the practical needs of very high-throughput biodosimetry in a variety of different large-scale exposure scenarios, to predict both individual dose and also individual sensitivity to future injury. A central characteristic remains our focus on 3 different high-throughput approaches: fully automated cytogenetics (Project 1), gene expression (Project 2), and metabolomics (Project 3). These have different balances of capabilities in terms of throughput, time-to-result, dose reconstruction, exposure scenario identification and individual radiosensitivity prediction, and the final goal is to quantify their optimal integrated usage in different large-scale exposure scenarios. The Projects share four common themes: 1: “Beyond Simple Exposures”: Towards High-Throughput Biodosimetry for Complex Exposures: After an IND there will be a wide variety of exposure scenarios including very high dose rate, neutron exposure, partial-body exposure (all from the initial prompt radiation), and varying dose rate and low dose rate (from external fallout and internal exposure). The goals are to 1) understand how these different exposure scenarios modulate the response of the predictive biomarkers that we have developed, and 2) optimally use these biomarkers to identify / characterize these different exposure scenarios to which individuals may be exposed. 2: “Beyond Dose”: Towards High-Throughput Individualized Predictors of Photon and Neutron- Induced Radiosensitivity and Late Radiation Injury: Gene expression and metabolomics each have utility for predicting individualized onset of late radiation-induced lung disease, and for predicting which irradiated animals will die from the disease. This work will be extended to neutron-induced late effects, whilst also assessing the significance of senescent cells for late disease development and for our lung disease signatures. 3: “Beyond Model Systems”: Probing the Applications of Experimentally-Generated Photon and Neutron Biomarkers to In-Vivo Human Exposure Scenarios: The goal is to assess in-vivo human exposures, but biodosimetric assay development is typically performed either with ex-vivo irradiated human blood or in-vivo in animals. For both photons and neutrons, ex-vivo vs. in-vivo generated biomarkers will be compared, and ex-vivo generated biomarkers from different species will be characterized and compared. 4: Optimized Biomarker Integration: The three different biomarker systems reflect different balances of capabilities in terms of, for example, throughput, time-to-result, signal lifetime, dose reconstruction, exposure scenario identification and individual radiosensitivity prediction. The goal here is to identify their optimal integrated usage in each of a variety of very different possible large-scale exposure scenarios. Three scientific cores (Animal, Irradiation & Dosimetry, and Biostatistics) bring together key support technologies, with each Core supporting each of the Research Projects. Because of the integrated nature of the research, this results in major gains in efficiency.