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人类寄生虫病。虽然使用了一种有效的抗血吸虫药物，但据估计，每年有2亿人感染，2 000万人患有严重的疾病症状，28万人死于血吸虫病。虽然已经确定了曼氏血吸虫和日本血吸虫的基因组序列，但大多数预测基因编码的蛋白质功能未知。为了充分利用基因组序列数据库，开发高效、可重复的功能基因组工具势在必行。在这个应用中，我们建议发展中等吞吐量的成像方法，使组织表达定位的基因。鉴于虫卵在血吸虫病生命周期传播和病理过程中的重要作用，本研究将重点研究虫卵生殖生物学相关基因的表达定位，这些基因是我们在虫卵发育过程中发现的。通过将未知功能的基因与已知功能的基因共定位，我们将能够了解它们的功能并开发蛋白质相互作用网络。寄生扁虫需要寄主来完成它们的生命周期，而且它们的功能基因组工具普遍不发达。因此，我们将确定是否可以使用具有完善的功能基因组工具箱的自由生活扁虫（Schmidtea mediterranea）来研究寄生扁虫的基本过程。我们的长期目标是确定控制血吸虫病的新药物靶点和候选疫苗。

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.