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.
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