日本血吸虫是对我国人民健康和经济社会发展威胁最严重的寄生虫。日本血吸虫的生物学特性极其复杂，可有效逃避宿主的免疫识别与攻击，并通过与宿主的相互作用满足自身生长需求。如血吸虫可接受终宿主合成的胰岛素作用，从而有利于自身的发育繁殖和免疫逃避，但人们对此仍缺乏系统研究，具体作用机制也知之甚少。本课题拟用链脲佐菌素诱导小鼠β细胞死亡构建I型糖尿病实验动物模型，研究胰岛素缺失状态下虫体的生长发育生殖状态变化，再通过转录组测序比较各生活史阶段虫体的基因表达差异，联合胰岛素结合蛋白质组鉴定，经过生物信息学分析，探寻宿主胰岛素参与日本血吸虫发育繁殖及免疫逃避的调控靶点。本研究将从日本血吸虫整体水平、蛋白质水平、基因水平三个不同的层面研究宿主胰岛素对虫体各项生理功能的作用，深入探讨宿主因子对日本血吸虫虫体发育繁殖的影响及其在免疫逃避中的作用机制，从而为设计基于日本血吸虫胰岛素受体的疫苗和药物提供理论支持。

Schistosomiasis japonica, which is caused by the parasitization of adult male and female blood flukes of Schistosoma japonicum, is the most devastating parasitic disease in China according to both morbidity and mortality. The fact that adult parasites can survive within the mesenteric or vesicular veins of their hosts for decades indicates that the worms employ a variety of strategies to escape identification by the immune system. Several authors have reported that schistosomes are affected by host hormones, including insulin, but the mechanisms of the interactions are still not well defined. This research project was designed to further investigate the importance of host insulin-schistosome interaction in the growth, development, sexual maturation and egg production of adult Schistosoma japonicum. Type I diabetes, characterized by insulin deficiency, can be induced by streptozotocin (STZ) injection to damage pancreatic beta cells specifically. Therefore, the following studies can be taken place in this animal model of hypoinsulinemia. Firstly, normal and insulin-deficient Balb/c mice will be infected with 40 cercariae. 42 days later, the eggs, schistosomula, male and female worms burden will be compared between these two groups. Secondly, gene expression analysis using transcriptome sequencing will be performed to measure the expression difference chart between normal and insulin-deficient rabbits during the four parasite developmental stages. Then, we will defined the insulin-binding proteome of adult worms using human insulin as the molecular bait for affinity purification, followed by protein identification by liquid chromatography with tandem mass spectrometry (LC-MS/MS). Finally, a comprehensive and systematic bioinformatics analysis of the above two databases will be performed, in order to search of key targets of host insulin action on growth and survival regulation. This project study the insulin-schistosome interaction from integral level, protein level and gene transcription level, to provide a global view of the functional mechanism between Schistosoma japonicum and human insulin, will facilitate the rational design of vaccines and drugs based on schistosomal insulin receptors.