MECHANISM OF HOST INVASION BY SCHISTOSOMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 确定血吸虫入侵宿主的分子机制将是开发合理的血吸虫病预防或控制方法的重要一步。我们感兴趣的是研究血吸虫幼虫对脂质的反应所形成的蛋白水解物促进宿主细胞外基质的降解和感染性幼虫进入宿主血液的生化和分子机制。该项目将化学蛋白质组学技术与最近可用的丰富的血吸虫基因组序列数据相结合，以检查促进宿主入侵的关键蛋白质成分。我们的方法包括蛋白质分离技术，然后对蛋白质进行质谱分析。然后，我们使用计算机图形实验室提供的生物信息学和序列分析工具来分析衍生的蛋白质序列。 一个相关的项目是研究用于消化宿主血红蛋白和其他血浆蛋白以及用于传播感染的血吸虫蛋白水解酶。具体地说，我们感兴趣的是绘制出血吸虫消化酶的生化激活级联反应。 一个新的项目已经启动：布氏锥虫重组组织蛋白B与转铁蛋白的相互作用和切割位点的鉴定。 对于这些项目，我们使用CGL资源进行血吸虫蛋白水解酶的结构建模和序列分析。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Characterization of the molecular mechanisms of host invasion by schistosomes will be an important step in developing rational approaches to prevention or control of schistosomiasis. Our interest is in studying the biochemical and molecular mechanisms by which a proteolytic mixture, elaborated by schistosome larvae in response to lipid, facilitates degradation of host extracellular matrix and entrance of infectious larvae into the host bloodstream. This project combines chemical proteomics techniques with the wealth of recently available schistosome genomic sequence data to examine the key protein components that facilitate host invasion. Our methods include protein separation techniques followed mass spectrometric analysis of the proteins. We then analyze the derived protein sequences using bioinformatics and sequence analysis tools available through the Computer Graphics Laboratory. A related project is in studying schistosome proteolytic enzymes used for digestion of the host hemoglobin and other plasma proteins and for propagation of infection. Specifically, we are interested in mapping out the biochemical activation cascade for the schistosome digestive proteases. A new project has been started: The interaction of Trypanasome brucei rec Cathepsin B with Transferrin and the identification of cleavage sites. For these projects, we use CGL resources for structural modeling and sequence analysis of the schistosome proteolytic enzymes.