High Throughput Proteome Analysis of Schistosoma mansoni

描述(由申请人提供)：蛋白质组学分析对于更好地了解寄生虫生物学的基本方面、指定从生物体基因组序列中识别的许多基因的功能是必不可少的，并将提供信息以帮助对基因组序列进行注释。这是一项建议使用高通量蛋白质组学方法来表征(1)曼氏血吸虫卵分泌的蛋白质补体，(2)存在于曼氏血吸虫成虫表面的蛋白质补体，以及(3)转化曼氏血吸虫尾蚴分泌的蛋白质补体。在蛋白质组学分析之后，我们将对鸡蛋分泌的蛋白质进行详细的研究。这项研究将使我们能够检验这样的假设，即鸡蛋释放的蛋白质在保护鸡蛋免受免疫介导的破坏方面发挥着重要作用，在组织传递中是重要的，是肉芽肿形成的主要免疫刺激因素。分泌蛋白和表面蛋白的特征将增加我们对血吸虫基本生物学的了解。我们将识别曼氏血吸虫用来促进入侵、存活和穿过宿主组织的蛋白质，并阐明肉芽肿形成的免疫学基础，以及血吸虫如何感知环境和与配偶沟通。这些结果可能被证明是有用的策略，以改善血吸虫病的病理反应，并在开发新的诊断，药物和疫苗。本申请中描述的高通量鸟枪蛋白质组学项目将使用多维蛋白质识别技术(MudPIT)分析蛋白质混合物。该项目的完成将提供曼氏沙门氏菌重要蛋白质互补的信息，并验证MudPIT在未来蛋白质组学研究中的使用，以确定曼氏沙门氏菌蛋白质组的全面情况。

DESCRIPTION (provided by the applicant): Proteomic analyses will be essential to better understand fundamental aspects of parasite biology, to assign the function of many genes identified from the genome sequence of an organism, and will provide information to aid in the annotation of the genome sequence. This is a proposal to use a high throughput proteomics approach to characterize protein complements that are (1) secreted by the eggs of Schistosoma mansoni (2) present on the surface of adult S. mansoni worms, and (3) secreted by transforming S. mansoni cercariae. We will follow the proteomic analysis with a detailed investigation of egg-secreted proteins. This study will allow us to test the hypothesis that proteins released by eggs play significant roles in protecting the egg from immune-mediated destruction, are important in tissue passage, and are major immuno-stimulants of granuloma formation. The characterization of secreted and surface proteins will increase our understanding of the basic biology of schistosomes. We will identify proteins used by S. mansoni to promote invasion, survival, and passage across host tissues and shed light on the immunological basis of granuloma formation and how schistosomes sense their environment and communicate with their mate. These results may prove to be useful in strategies to ameliorate pathologic responses in schistosomiasis and in the development of novel diagnostics, drugs and vaccines. The high throughput shotgun proteomics project described in this application will analyze protein mixtures using multidimensional protein identification technology (MudPIT). Completion of this project will provide information on significant protein complements of S. mansoni and also validate the use of MudPIT in future proteomic studies to define a comprehensive view of the S. mansoni proteomes.