High Throughput Proteome Analysis of Schistosoma mansoni

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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.