Radiation Biodosimetry using Gene Expression Signatures

项目2：使用基因表达签名进行辐射生物剂量测定。基因表达代表着一种 生物剂量测定的实用方法，但研究通常只集中在急性外部光子 曝光。差异基因表达反应可能是由其他类型的暴露引起的 放射学分类，仍需要大量工作来完善基于基因表达的签名 适用于辐射暴露复杂情况下的生物剂量测定。建议数 研究将表征剂量率、内部发射体137Cs和 简易核装置(IND)辐射对与辐射生物剂量学相关的基因表达的反应。 此外，剂量估计只提供了一年中预期的平均辐射伤害的大致概念。 人群中，个体辐射损伤反应和结果的预测因子可能更多 很有用。放射性肺损伤死亡风险个体化的血液转录预测因子 将开发出肺损伤和恢复的基因表达特征。炎症过程 被辐射激活，是导致晚期疾病的重要因素。慢性炎症性 条件或免疫抑制也有可能混淆辐射生物剂量学特征。 个人，因此将开始调查炎症途径对生物剂量学特征的影响 使用鼠标模型。 所有拟议的研究最终都指向开发实用的生物剂量学解决方案 紧急放射学分诊。为了支持这一更大的目标，集成的血液采集设备兼容 将与Sample Engineering Core合作测试其交付能力 高质量的样品，用于下游测量方法量化mRNA水平。这将开始 为了解决样本收集问题，一个被忽视的关键瓶颈是实施基于基因表达的 辐射生物剂量学。 这个项目中建议的基因表达谱研究将得到以下研究的补充 利用共享生物样本的细胞遗传学终点(项目1)和代谢组学分析(项目3) 和实验设计。这些核心将进一步加强计划中的研究，通过集中和 标准化常规功能，如鼠标处理和照射，并通过提供独特的资源， 如内能谱中子源和可变剂量率外137Cs辐照器(辐照堆芯)， 和用于生物剂量测定的血液学人源化小鼠(Mouse Core)。

Project 2: Radiation Biodosimetry using Gene Expression Signatures. Gene expression represents a practical approach to biodosimetry, but studies have generally focused only on acute external photon exposure. Differential gene expression responses may result from other types of exposures important for radiological triage, and much work will still be required to refine signatures for gene expression-based biodosimetric assays for application in situations where the radiation exposure is complex. The proposed studies will characterize contributions of dose rate, the internal emitter 137Cs, and the neutron component of improvised nuclear device (IND) radiation to gene expression responses relevant to radiation biodosimetry. Furthermore, dose estimates provide only a general idea of the average radiation injury expected across a population, with predictors of individual radiation injury response and outcome potentially being even more useful. Blood-based transcriptomic predictors for individualized risk of death from radiation-induced lung injury will be developed, as well as gene expression signatures of lung injury and recovery. Inflammatory processes are activated by radiation exposure and are important contributors to late disease. Chronic inflammatory conditions or immunosuppression also have the potential to confound radiation biodosimetric signatures in individuals, so investigation of the impact of inflammatory pathways on biodosimetric signatures will be initiated using mouse models. All the proposed research is ultimately directed toward developing practical biodosimetry solutions for emergency radiological triage. In support of this larger goal, an integrated blood collection device compatible with self-administration will be tested in collaboration with the Sample Engineering Core for its ability to deliver high quality samples for quantification of mRNA levels by downstream measurement methods. This will begin to address sample collection, a key neglected bottleneck for implementation of gene expression-based radiation biodosimetry. The gene expression profiling studies proposed in this project will be complemented by investigations of cytogenetic endpoints (Project 1) and metabolomic profiling (Project 3) leveraging shared biological samples and experimental designs. The Cores will further enhance the planned research by centralizing and standardizing routine functions, such as mouse handling and irradiations, and by providing unique resources, such as the IND-spectrum neutron source and the variable dose rate external 137Cs irradiator (Irradiation Core), and the hematopoietically humanized mouse for biodosimetry (Mouse Core).