Development of a functional genomics toolbox for schistosome parasites

描述(申请人提供)：血吸虫病是一种重要的热带寄生虫病。虽然一种有效的抗血吸虫病药物正在使用中，但据估计，每年有2亿人感染，2000万人出现严重的疾病症状，28万人死于血吸虫病。虽然曼氏血吸虫和日本血吸虫的基因组序列已经确定，但大多数预测的基因编码功能未知的蛋白质。为了充分利用基因组序列数据库，开发高效和可重复性的功能基因组学工具势在必行。在这项应用中，我们建议开发中等吞吐量的成像方法，使基因的组织表达定位成为可能。由于虫卵在血吸虫病的生命周期和病理传播中的重要性，本建议侧重于虫子生殖生物学中涉及的基因的表达定位，这是我们在对虫子发育的转录分析中确定的。通过将未知功能的基因与已知功能的基因共定位，我们将能够理解它们的功能，并建立蛋白质相互作用网络。寄生扁虫需要宿主来完成它们的生命周期，并且通常没有开发出功能强大的基因组工具。因此，我们将确定一种具有成熟功能基因组工具箱的自由生活扁虫是否可以用于研究寄生扁虫的基本过程。我们的长期目标是确定血吸虫病控制的新药物靶点和候选疫苗。 公共卫生意义：血吸虫病是一种重要的被忽视的热带寄生虫病，影响着2.5亿多人，每年在70多个国家造成超过25万人死亡。虽然曼氏血吸虫和日本血吸虫的基因组序列已经确定，但大多数预测的基因编码未知功能的蛋白质。为了充分利用基因组序列数据库，开发高效和可重复性的功能基因组学工具势在必行。在这项应用中，我们建议开发中等吞吐量的成像方法来实现组织表达定位，并确定具有良好功能的基因组工具箱的自由生活扁虫是否可以用于研究寄生扁虫的基本过程。

DESCRIPTION (provided by applicant): Schistosomiasis is an important tropical parasitic human disease. Although an effective anti-schistosome drug is in use, it is estimated that 200 million people are infected, 20 million individuals suffer severe disease symptoms, and 280,000 people die annually from schistosomiasis. Although the genome sequences of Schistosoma mansoni and S. japonicum have been determined, most predicted genes encode proteins with unknown function. In order to make full use of the genome sequence databases it is imperative to develop efficient and reproducible functional genomic tools. In this application we propose to develop moderate throughput imaging methodologies that will enable tissue expression localization of a gene. Because of the importance of the worm egg in transmission of the lifecycle and pathology of schistosomiasis, this proposal focuses on expression localization of genes involved in reproductive biology of the worm, which we have identified in a transcriptional analysis of worm development. By co-localizing genes of unknown function with genes with known functions we will be able to understand their functions and to develop protein interacting networks. Parasitic flatworms require a host to complete their lifecycles and have generally poorly developed functional genomic tools. Therefore, we will determine if a free living flatworm with a well-developed functional genomic toolbox, Schmidtea mediterranea, can be used to investigate fundamental processes in parasitic flatworms. Our long-term goals are to identify new drug targets and vaccine candidates for schistosomiasis control. PUBLIC HEALTH RELEVANCE: Schistosomiasis is an important neglected tropical parasitic disease affecting more than 250 million people and causing more than a quarter of a million deaths annually in over 70 countries. Although the genome sequences of Schistosoma mansoni and S. japonicum have been determined, most predicted genes encode proteins of unknown function. In order to make full use of the genome sequence databases it is imperative to develop efficient and reproducible functional genomic tools. In this application we propose to develop moderate throughput imaging methodologies to enable tissue expression localization and to determine if a free living flatworm with a well-developed functional genomic toolbox, Schmidtea mediterranea, can be used to investigate fundamental processes in parasitic flatworms.