Transcriptomes and Proteomes of Plasmodium Vivax

 描述(申请人提供)：间日疟原虫是第二大流行和地理分布最广的疟疾寄生虫，在受影响人口中造成巨大的发病率和死亡率。对间日疟原虫的研究严重滞后，这主要是由于缺乏连续的体外培养系统。这种寄生虫选择性地入侵网织红细胞，使长期培养变得困难。负责传播的间日疟原虫配子体是在临床症状出现之前产生的。虽然第一个间日疟原虫基因组已于2008年发表，但对无性红细胞周期的转录本和蛋白质组的系统比较缺乏，而且我们对间日疟原虫配子体的发育生物学知之甚少。本项目基于人源化小鼠模型研究间日疟原虫肝脏发育阶段的最新进展和我们改进的血液同步体外培养技术，旨在分别使用RNA测序和质谱仪技术来确定间日疟原虫红细胞无性发育和配子细胞发生过程中的时间转录和蛋白质组。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这种被忽视的疟疾寄生虫无性和有性发育的基本生物学问题。这些信息也被认为是发现阻断间日疟原虫传播的新药和疫苗的关键。

 DESCRIPTION (provided by applicant): Plasmodium vivax is the second most prevalent and the most geographically widespread malaria parasite, causing enormous morbidity and mortality in affected populations. Research on P. vivax malaria has lagged significantly behind, largely due to the lack of a continuous in vitro culture system. This parasite selectively invades reticulocytes, making long-term culture difficult. P. vivax gametocytes, which are responsible for transmission, are produced before the onset of the clinical symptoms. Though the first P. vivax genome was published in 2008, systematic comparison of the transcriptomes and proteomes of the asexual erythrocytic cycle is lacking and we know little about the developmental biology of P. vivax gametocytes. This project, built on recent advancement in humanized mouse model to study the liver stages of this parasite and our improved in vitro culture techniques for synchronous blood stages, aims to determine the temporal transcriptomes and proteomes during P. vivax asexual erythrocytic development and gametocytogenesis using RNA sequencing and mass spectrometry technologies, respectively. The comprehensive transcriptomic and proteomic data generated from this study will enable systems biology approaches to address the fundamental biology of asexual and sexual development of this neglected malaria parasite. This information is also deemed critical for the discovery of novel drugs and vaccines for the interruption of P. vivax transmission.