Regulation of gene expression in Plasmodium

描述（由申请方提供）：恶性疟原虫引起最致命的人类疟疾。血液期寄生虫包括形态上不同的环，滋养体和滋养体阶段，具有不同的基因表达模式。例如，表面粘附变异基因（因其在发病机制中的作用而引起特别的兴趣）在环中显示混杂转录，但在滋养体中表达受限。然而，对于VAR和其他疟原虫基因，基因表达是否在转录水平、信息稳定性以及由UTR中的序列元件介导进行调节还知之甚少。本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真核生物低水平基因表达和在疾病病理学中起重要作用的基因（如vars）的调控的基本理解。分子，遗传学工具，包括转染表达启动子融合，结合生化亚细胞分级分析，将用于确定基因调控的元素。var调节的独特机制可能提供对抗脑型疟疾的靶点。

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.