Chlamydia trachomatis proteomics

现有的衣原体基因组序列使在整个基因组范围内研究衣原体成为可能。例如，对基因组序列的比较揭示了衣原体基因的功能与其在其他物种中的同源性，并为衣原体的进化史提供了信息。全基因组的基因转录谱分析已经将基因表达模式与生物反应联系起来。然而，这些基于核酸序列的分析在充分了解衣原体蛋白的功能方面存在局限性。由于缺乏对衣原体的基因操作，研究人员被迫在异源系统中开发功能驱动的全基因组筛查方法。虽然这些分析中有一些产生了有用的信息，但许多都收效甚微。 为了补充上述鉴定衣原体蛋白功能的方法，我们 提出了一种功能蛋白质组学方法，其中将发展全基因组蛋白质阵列分析来识别人类衣原体感染过程中的保护性和致病决定因素，并确定蛋白质-蛋白质相互作用对。此外，还将产生抗体来表征内源性衣原体蛋白的表达水平/模式、半衰期、翻译后修饰、相互作用伙伴和细胞内定位。 这些拟议的研究将为了解衣原体的致病机制和制定控制衣原体感染引起的疾病的干预和预防策略提供必要的信息。

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.