Inflammation and the Host Response to Injury

描述(由申请人提供)：宿主对创伤的反应和 烧伤是一个高度复杂的生物和病理过程，依赖于 关键在于对人类免疫炎症反应的调节。这 大型协同项目将应用高通量生物 发现工具，用于识别重要的动态关系，这些关系调节 将这些复杂的流程集成在一起，期望这一新的 知识最终将影响烧伤和创伤患者的治疗。一个 高度互动的调查小组，兴趣重叠，独一无二 技术将为这一努力做出贡献。具体目标是：(1) 确定免疫炎症性宿主反应中的一组表型 使用可测试的、共识派生的范式来描述四个 受伤患者的独立临床康复轨迹。 (2)确定作为免疫炎症的结果的基因表达模式 循环外周血白细胞对损伤的宿主反应。(3)识别 基因之间的关系，以及基于时间的基因聚类 表情模式。(四)确定关联度和程度 烧伤和严重创伤小鼠模型的区划。至 要实现这些总体科学目标，在 这个大规模的协作项目，以及这些任务的完成 将成为该项目的里程碑。除了其他里程碑之外， 这些措施包括：(1)为患者治疗制定和发布SOP， 病人样本的处理，以及蛋白质和蛋白质的分析程序 细胞学研究；(2)确定患者的免疫炎症表型 有损伤；(3)确定基因或 寄主对伤害的反应中的共同调节基因，并提示有成果的区域 用于未来的研究；(4)确定小鼠模型与 严重创伤的人类表型；(5)确定两者是否存在相关性 亚细胞群体中的蛋白质和基因组反应与 循环外周血白细胞总数及循环间 白细胞和外周组织中的白细胞；以及(6)测定和发布 创伤人群中常见的SNPs频率。这些 里程碑将通过制定一项行政、 信息传播和数据协调以及计算分析和 建模核心，此外还有四个科学核心。

DESCRIPTION (provided by applicant): The host response to trauma and burns is a highly complex biological and pathological process that depends critically upon the regulation of the human immuno-inflammatory response. This large-scale collaborative project will apply high throughput biological discovery tools to identify important dynamic relationships, which regulate the integration of these complex processes with the expectation that this new knowledge will ultimately impact the treatment of burn and trauma patients. A highly interactive group of investigators with overlapping interests and unique technologies will contribute to the effort. The specific aims are: (1) Determine the set of phenotypes seen in the immuno-inflammatory host response to injury using a testable, consensus-derived paradigm which describes four independent clinical recovery trajectories of patients suffering from injury. (2) Identify gene expression patterns as a result of the immuno-inflammatory host response to injury in circulating peripheral leukocytes. (3) Identify relationships among genes, and the clustering of genes based upon temporal expression patterns. (4) Determine the relevance and degree of compartmentalization in murine models of burn and severe trauma injury. To accomplish these overall scientific goals, there are multiple tasks proposed in this large-scale collaborative project, and the accomplishment of these tasks will serve as milestones for the project. In addition to other milestones, these include: (1) Develop and publish SOPs for patient treatments, the handling of patient samples, and the analytical procedures for protein and cellular studies; (2) Determine the immuno-inflammatory phenotypes of patients with injury; (3) Determine potential relationships between genes or co-regulated genes in the host response to injury and suggest fruitful areas for future investigation; (4) Determine the relevance of murine models to the human phenotypes of severe injury; (5) Determine whether there are correlations between protein and genomic responses in subcellular populations versus the total pool of circulating peripheral leukocytes and between circulating leukocytes and those in peripheral tissues; and (6) Determine and publish the frequency of common SNPs in the ethnic groups who suffer from trauma. These milestones will be accomplished through the development of an administrative, information dissemination and data coordination, and computational analysis and modeling core, in addition to four scientific cores.