Sex-Specific Gene Expression in Malaria Parasite Plasmodium falciparum

随着财政和技术支持的改善，许多疟疾流行国家再次考虑将消除疟疾作为其疟疾控制的国家目标。为了实现这一宏伟目标，最大的挑战之一是在全世界阻断疟疾传播。疟原虫的性发育对于疟原虫通过蚊子传播至关重要。尽管它在生命中扮演着重要角色 尽管疟疾寄生虫的周期很短，但性发育机制仍然知之甚少，这一知识差距严重阻碍了阻断疟疾传播的新工具的开发。这个项目，建立在我们最近成功地创建恶性疟原虫线与男性或女性配子体标记的报告基因，旨在确定配子体的两性之间的分子差异。从这项研究中产生的综合转录组学和蛋白质组学数据将使系统生物学方法能够解决疟疾寄生虫性别分化的基本生物学问题。这一信息对于开发阻断疟疾传播的新药和疫苗也至关重要。 公共卫生相关性：性发育是通过蚊子传播疟疾寄生虫的必要条件。阻断疟疾传播被认为是消除疟疾阶段的最大挑战之一。然而，疟原虫性别分化的机制仍然知之甚少。该项目是建立在我们最近成功地遗传操纵有性阶段寄生虫，并整理出配子体阶段的两性，旨在确定男性和女性之间的差异寄生虫使用先进的高通量基因表达和蛋白质鉴定方法。

DESCRIPTION (provided by applicant): With improved financial and technical supports, many malaria endemic nations are once again considering malaria elimination as their national goal of malaria control. To achieve this ambitious goal, one of the greatest challenges is interruption of malaria transmission worldwide. Sexual development of malaria parasite is essential for transmission of the parasite through mosquitoes. Despite its central role in the life cycle of malaria parasites, the mechanism of sexual development is still poorly understood, and this knowledge gap severely hinders the development of novel tools to interrupt malaria transmission. This project, built on our recent success in creating Plasmodium falciparum lines with male or female gametocytes tagged with a reporter gene, aims to determine the molecular differences between the two sexes of gametocytes. The comprehensive transcriptomic and proteomic data generated from this study will enable systems biology approaches to address the fundamental biology of sexual differentiation in malaria parasites. This information is also deemed critical for the development of novel drugs and vaccines for the interruption of malaria transmission. PUBLIC HEALTH RELEVANCE: Sexual development is obligatory for the transmission of malaria parasites through mosquito vectors. Interruption of malaria transmission is considered one of the greatest challenges during the malaria elimination phase. However, the mechanism of sexual differentiation in malaria parasites is still poorly understood. This project is built onour recent success to genetically manipulate the sexual stage parasites and to sort out the two sexes of the gametocyte stages, aiming to determine the differences between the male and female parasite using advanced high-throughput gene expression and protein identification approaches.