Regulation of gene expression in Plasmodium

描述(由申请人提供)：恶性疟原虫引起最致命的人类疟疾。血液期寄生虫由形态不同的环状、滋养体和裂殖体组成，具有不同的基因表达模式。例如，表面黏附var基因(因其在致病机制中的作用而引起特别关注)在环中显示出错配转录，但在滋养体中的表达受到限制。然而，在VARs和其他原生生物基因中，基因的表达是否在转录水平、信息稳定性和UTRs中由序列元件调控，目前还知之甚少。该项目的长期目标是了解恶性疟原虫阶段特异性基因调控的机制。这项研究将有助于我们对低真核基因表达的基本了解，以及对vars等在疾病病理中发挥重要作用的基因的调控。分子和遗传工具，包括表达启动子融合的转基因，结合生化亚细胞分级分析，将被用来识别基因调控的要素。VaR调节的独特机制可能为防治脑型疟疾提供靶点。

DESCRIPTION (provided by the applicant): Plasmodium falciparum causes the most virulent of human malarias. The blood stage parasites comprise of morphologically distinct ring, trophozoite and schizont stages with distinct patterns of gene expression. For instance, the surface adhesion var genes (that have attracted particular interest for their role in pathogenesis) show promiscuous transcription in rings but restricted expression in trophozoites. However whether gene expression is regulated at the level of transcription, message stability and mediated by sequence elements in the UTRs is poorly understood for both VARs and other plasmodial genes. The long-term goals of this project are to understand mechanisms of stage specific gene regulation in Plasmodium falciparum. The study will contribute to our basic understanding of lower eukaryotic gene expression and the regulation of genes such as vars that play an important role in disease pathology. Molecular, genetic tools including transfection to express promoter fusions, combined with biochemical subcellular fractionation assays, will be used to identify elements of gene regulation. Unique mechanisms in var regulation may provide targets against cerebral malaria.