Sex-Specific Gene Expression in Malaria Parasite Plasmodium falciparum

描述(申请人提供)：随着资金和技术支持的改善，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。为了实现这一雄心勃勃的目标，最大的挑战之一是阻断疟疾在全球的传播。疟疾寄生虫的有性发育对于该寄生虫通过蚊子传播至关重要。尽管它在生活中扮演着核心角色 在疟疾寄生虫的周期中，性发育的机制仍然知之甚少，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用带有报告基因的雄性或雌性配子体建立恶性疟原虫品系的基础上，旨在确定两性配子体之间的分子差异。这项研究产生的全面的转录组和蛋白质组数据将使系统生物学方法能够解决疟疾寄生虫性分化的基本生物学问题。这一信息也被认为对开发用于阻断疟疾传播的新药和疫苗至关重要。 与公共卫生相关：性发育是通过蚊媒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，疟疾寄生虫性分化的机制仍然知之甚少。这个项目是建立在我们最近成功地对有性阶段的寄生虫进行遗传操作并区分配子体阶段的两性的基础上的，目的是利用先进的高通量基因表达和蛋白质鉴定方法来确定雄性和雌性寄生虫之间的差异。

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.