Gene Expression Profiling Core

被感染的宿主细胞对有害的细胞内病原体的动态反应是感染的自然历史和结果的关键决定因素。这些反应反映并导致基因表达的变化，可以提供对宿主-病原体相互作用中心的途径和过程的分子洞察。因此，对项目1-4的研究至关重要的是一套资源，用于比较宿主巨噬细胞对不同的细胞内病原体及其分子决定因素做出反应的全基因组表达谱。这项提案的目的是提供必要的资源和工具，以产生和比较小鼠巨噬细胞对一组细胞内病原体(分别对应于项目1-4的结核分枝杆菌、组织胞浆菌、图拉氏弗朗西斯杆菌和单核细胞增生性李氏杆菌)的基因组规模表达反应。这些 资源包括设计、生产和分配基于使用新策略选择的长寡核苷酸的小鼠DNA微阵列，该策略将几乎完整的小鼠基因组序列与数百万的mRNA和EST序列相结合。除了使用标准化方法为这些感染过程生成表达谱外，这些微阵列的使用在很大程度上依赖于开发和维护相应的生物信息学基础设施，以存储、分析、分析和传播方案参与者产生的大量数据。因此，核心B的目标是创建和维护一个安全、健壮和用户友好的储存库，以存储、检索、分析、显示和传播微阵列数据。此外，核心B将为调查人员提供统计支持 研究设计和分析计划，以及培训和支持计划参与者设计、执行和分析微阵列实验。

The dynamic responses of infected host cells to an offending intracellular pathogen are a pivotal determinant of the natural history and outcome of infection. These responses both reflect and result in gene expression changes that can provide molecular insight into the pathways and processes central to the host-pathogen interaction. Therefore, essential to the studies of Projects 1-4 are a set of resources for comparing the genome-wide expression profiles of host macrophages responding to distinct intracellular pathogens and their molecular determinants. The aim of this proposal is to provide the necessary resources and tools required for generating and comparing genome-scale expression responses of murine macrophages responding to a group of intracellular pathogens (Mycobacterium tuberculosis, Histoplasma capsulatum, Francisella tularensis, and Listefia monocytogenes, corresponding to Projects 1-4, respectively). These resources include the design, production, and distribution of mouse DNA microarrays based on long oligonucleotides selected using a novel strategy that combines the nearly complete mouse genome sequence with millions of mRNA and EST sequences. In addition to the use of standardized methods for generating expression profiles for these infection processes, the utility of these microarrays relies heavily on the development and maintenance of a corresponding bioinformatics infrastructure for the storage, analysis, in distribution of the bodies of data generated by the Program participants. Accordingly, Core B aims to create and maintain a secure, robust and user-friendly repository to store, retrieve, analyze, display and disseminate microarray data. Furthermore, Core B will provide statistical support for the investigators in the Program for study design and analyses, as well as train and support Program participants in the design, execution, and analysis of microarray experiments.