Inflammation and the Host Response to Injury

描述（由申请人提供）：宿主对创伤的反应， 烧伤是一种高度复杂的生物和病理过程， 关键在于人类免疫炎症反应的调节。这 大规模合作项目将应用高通量生物 发现工具，以确定重要的动态关系，这规范了 整合这些复杂的过程，期望这个新的 知识将最终影响烧伤和创伤患者的治疗。一 一组高度互动的调查人员，他们的兴趣重叠， 技术将有助于这一努力。具体目标是：（1） 确定免疫炎症宿主反应中观察到的表型集 使用一个可测试的，共识衍生的范式，描述了四个伤害 独立的临床康复轨迹的患者遭受伤害。 (2)确定免疫炎症反应导致的基因表达模式 宿主对循环外周血白细胞损伤的反应。(3)识别 基因之间的关系，以及基于时间的基因聚类 表达模式(4)确定的相关性和程度 烧伤和严重创伤损伤小鼠模型中的区室化。到 为了实现这些总体科学目标， 这个大规模的合作项目，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， 这些措施包括：（1）制定和公布病人治疗的标准操作规程， 患者样本的处理，以及蛋白质和 细胞研究;（2）确定患者的免疫炎症表型 （3）确定基因之间的潜在关系， 共调节基因在宿主对损伤的反应，并建议富有成效的领域 （4）确定小鼠模型与研究的相关性。 严重损伤的人类表型;（5）确定是否存在相关性 亚细胞群体中蛋白质和基因组反应与 循环外周血白细胞总池和循环间 白细胞和外周组织中的白细胞;（6）确定并公布 遭受创伤的种族群体中常见SNP的频率。这些 里程碑将通过建立一个行政， 信息传播和数据协调以及计算分析， 除了四个科学核心之外，还有一个建模核心。

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.