Multi-Omics Characterization of Plasmodium Vivax Hypnozoites

摘要 间日疟原虫寄生虫威胁着世界上一半的人口， 消灭疟疾的努力，部分原因是它们能够在肝脏中作为催眠虫休眠数周， 个月在这里，我们建议进行最先进的转录组学，表观基因组学和脂质组学分析， 从感染间日疟原虫的非人灵长类动物收集的材料，以及人肝细胞的体外感染 患者来源的间日疟原虫子孢子。我们的分析将提供一个全面的视角， 间日疟原虫休眠的发生、维持和退出的分子和细胞机制，以及 从受感染的肝细胞到整个器官和生物体的反应。我们 研究结果不仅可以更好地了解命运的基本过程， 发展肝脏阶段的间日疟原虫寄生虫，但也将提供一个坚实的基础，发展更好的疟疾 针对这种重要但研究不足的人类病原体的疫苗和疗法。

Abstract Plasmodium vivax parasites threaten half of the world’s population and are surprisingly resilient to on-going malaria elimination efforts, partially due to their ability to remain dormant in the liver as hypnozoites for weeks or months. Here, we propose to conduct state-of-the-art transcriptomic, epigenomic and lipidomic analyses using materials collected from non-human primates infected with P. vivax, and in vitro infections of human hepatocytes with patient-derived P. vivax sporozoites. Our analyses will provide a comprehensive perspective on the molecular and cellular mechanisms underlying the onset, maintenance and exit of P. vivax dormancy, and well as on the response of the host, from the infected hepatocytes to the organ- and organism-wide responses. Our findings will not only provide a better understanding of the fundamental processes underlying the fate and development of liver-stage P. vivax parasites but will also provide a solid foundation to develop better malaria vaccines and therapies against this important but understudied human pathogen.