Chlamydia trachomatis proteomics

描述（由申请人提供）：C。沙眼衣原体蛋白质组学：沙眼衣原体全基因组定位。沙眼保护性和致病性决定因素。泌尿生殖道沙眼衣原体感染引起上生殖道炎症性病变，可导致包括输卵管因素不孕在内的并发症。了解衣原体的致病机制和研制亚单位疫苗是当前衣原体研究的热点。然而，衣原体的发病机制的知识仍然有限，并没有有效的疫苗。这可能主要是由于以前用于分析衣原体抗原的方法的局限性。尽管这些先前的方法提供了有用的信息，例如，揭示了抗MOMP抗体应答与保护性免疫和抗HSP 60抗体应答与发病机制的关联，但结果在范围上是有限的。为了在了解衣原体致病机制和开发有效的亚单位疫苗方面取得重大进展，钟博士的实验室表达了所有的衣原体。沙眼衣原体开放阅读框架（ORF）作为可溶性融合蛋白，并在过去5年中开发了高质量的全基因组规模蛋白质组阵列。该阵列允许检测线性和构象依赖性人抗体。利用这个阵列，钟博士的实验室已经绘制了B细胞抗原组，并鉴定了新的C.沙眼在目前的资助中，钟博士将使用全基因组规模的蛋白质组阵列来描述C.沙眼衣原体感染的妇女，并确定与病理或保护性免疫相关的抗原。将在细胞培养和动物模型系统中表征所鉴定抗原的生物学相关性。从拟议的研究中获得的知识和积累的试剂将提供给研究界。所获得的信息将为了解衣原体的致病机制以及开发诊断试剂和亚单位疫苗奠定基础。

DESCRIPTION (provided by applicant): C. trachomatis proteomics: Whole genome scale mapping of C. trachomatis protective & pathogenic determinants. Chlamydia trachomatis urogenital tract infection causes inflammatory pathologies in the upper genital tract, which can lead to complications including tubal factor infertility. Understanding the pathogenic mechanisms and developing subunit vaccines have been the major focuses in modern chlamydial research. However, knowledge on chlamydial pathogenesis remains limited and there is no effective vaccine. This may be mainly due to limitations in the approaches previously used for analyzing chlamydial antigens. Although these previous approaches have provided useful information, for example, revealing the association of anti-MOMP antibody responses with protective immunity and anti-HSP60 antibody responses with pathogenesis, the results are limited in scope. To make significant advancements in understanding chlamydial pathogenic mechanisms and developing effective subunit vaccines, Dr. Zhong's lab expressed all C. trachomatis open reading frames (ORFs) as soluble fusion proteins and developed a high quality whole genome scale proteome array in the past 5 years. This array has allowed the detection of both linear and conformation-dependent human antibodies. Using this array, Dr. Zhong's lab has mapped the B cell ANTIGENome and identified novel immunodominant antigens of C. trachomatis. In the current grant, Dr. Zhong will use the whole genome scale proteome array to profile the antigen specificities of both antibody and T cell responses in C. trachomatis infected-women and to identify antigens that are associated with pathology or protective immunity. The biological relevance of the identified antigens will be characterized in both cell culture and animal model systems. Both the knowledge gained and reagents accumulated from the proposed studies will be made available to the research community. The information obtained will lay the foundation for both understanding chlamydial pathogenic mechanisms and developing diagnostic reagents and subunit vaccines.