The available chlamydial genome sequences have made it possible to study chlamydia at the whole genome scale. For example, comparison of genome sequences have revealed functions of chlamydial genes with homologies to their counterparts in other species and provided information for chlamydial evolutionary history. Genome wide analyses of gene transcriptional profiles have correlated gene expression patterns with biological responses. However, these nucleic acid sequence-based analyses have limitations in fully understanding the functions of chlamydial proteins. Due to a lack of genetic manipulation for chlamydia, researchers are forced to develop function-driven genome wide screening assays in heterologous systems. While some of these assays have yielded useful information, many have met little success. To complement the above approaches for identifying functions of chlamydial proteins, we are proposing a functional proteomics approach, in which whole genome protein array assays will be developed for identifying protective and pathogenic determinants during human chlamydial infection and determining protein-protein interaction pairs. Furthermore, antibodies will be produced for characterizing endogenous chlamydial proteins for expression levels/patterns, half-life, post-translational modifications, interaction partners and intracellular localization. These proposed studies will provide essential information for understanding chlamydial pathogenic mechanisms and developing intervention and prevention strategies for controlling chlamydial infection-induced diseases.
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