In order to define the critical determinants of successful vaccination, it is crucial to identify the globalsignatures of the associated immune response. We propose to identify these signatures through theapplication of a combination of high-throughput mRNA technologies, proteomic technologies, andcomputational tools.
The aim of the genomics core is to provide high-throughput sequencing and microarray facilities forinvestigators in the vaccine consortium. Sequencing facilities will be available to analyze cDNA libraries,which will be utilized for customized array construction. The microarray facilities will be used for analysis ofmRNA expression profiles in populations of different immune cells under various stimulatory conditions.
The aim of the proteomics core is to assist the center investigators in quantitatively defining proteomicchanges in immune cells as they respond to immunization. The focus of the analyses is to characterizespecific changes within the proteomes of immune cells (T and B lymphocytes and dendritic cells), and withinpatients' sera. These studies aim to elucidate changes in membrane glycoproteins (co-stimulation andtrafficking), cytosolic phosphoproteins (signal transduction), and nuclear proteins (gene expression andcellular differentiation). Serum glycoproteins will be quantitated at early and later time points postimmunizationto identify humoral factors that correlate with the development of an effective memory immuneresponse.The bioinformatics core will provide a central repository for the storage of data in a standardized format,which will permit data from a variety of different techniques to be analyzed, integrated and shared betweeninvestigators. The core will provide software tools to enable researchers to explore the data, makecomparisons between data sets, to interrogate data sets with specific hypotheses, and to globally interrogatedata sets to identify novel patterns and associations among disparate data sources. Tools also will beprovided to simultaneously visualize and integrate multi-dimensional data sets. These computational toolswill be essential for extracting meaningful insight from the relationships between individual molecules andsystemic, immune responses to vaccination.
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