MECHANISM OF HOST INVASION BY SCHISTOSOMES

血吸虫宿主入侵机制

• 批准号: 7955486
• 负责人: James H. McKerrow
• 金额: $ 0.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-01 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7955486
• 关键词: Amino Acid Sequence; Biochemical; Bioinformatics; Blood Circulation; Cathepsins B; Chemicals; Computer Graphics; Computer Retrieval of Information on Scientific Projects Database; Data; Digestion; Extracellular Matrix; Funding; Genomics; Grant; Hemoglobin; Imagery; Infection; Informatics; Institution; Laboratories; Larva; Lipids; Maps; Methods; Molecular; Peptide Hydrolases; Peptide Sequence Determination; Plasma Proteins; Prevention approach; Protein Analysis; Proteins; Proteomics; Research; Research Personnel; Resources; Schistosoma; Schistosomiasis; Sequence Analysis; Site; Source; Structural Models; Techniques; Transferrin; United States National Institutes of Health; biocomputing; interest; response; tool

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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 因此，对血吸虫入侵宿主的分子机制的研究将是血吸虫病防治的重要一步。我们的兴趣是在研究的生物化学和分子机制，其中的蛋白水解混合物，阐述了由寄生虫幼虫在响应脂质，促进宿主细胞外基质的降解和入口的感染性幼虫进入宿主血流。 该项目将化学蛋白质组学技术与最近获得的大量基因组序列数据相结合，以研究促进宿主入侵的关键蛋白质组分。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，我们使用生物信息学和计算机图形实验室提供的序列分析工具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传播感染的溶酶体蛋白水解酶。 具体来说，我们感兴趣的是绘制出的生化激活级联的酶体消化蛋白酶。 一个新的项目已经开始：布氏锥虫rec组织蛋白酶B与转铁蛋白的相互作用和切割位点的鉴定。 在这些项目中，我们使用CGL资源进行蛋白酶体蛋白水解酶的结构建模和序列分析。