Transcriptional Regulation in Plasmodium falciparum

描述(申请人提供)：人类疟疾是由感染引起的 由原生动物寄生虫疟原虫sp.目前，有3-5亿人 感染疟疾，每年有150-350万人死于 疾病。尽管许多恶性疟原虫基因的表达参与了 发病和发育是在转录水平上调节的，有 几乎没有关于这些生物体中转录的机械性信息。 因此，三个恶性疟原虫热休克基因的转录将被分析为 一个模范系统。将使用分析中的核运行来确定 在没有和存在热应激的情况下这些基因的转录速率。 体内报告分析将用于确定启动子序列 是转录所必需的。需要热转录的蛋白质 休克基因将通过DNA亲和层析纯化，并通过 质谱学。这些研究将加深我们对 在恶性疟原虫中的转录，并允许更好地理解 这种寄生虫的发病机制、分化和耐药性。

DESCRIPTION (provided by the applicant): Human malaria results from infection by the protozoan parasite Plasmodium sp. Currently, 300-500 million peoples are infected with malaria, and 1.5-3.5 million individuals succumb annually to the disease. Although expression of many P. falciparum genes involved in pathogenesis and development are regulated at the level of transcription, there is little mechanistic information regarding transcription in these organisms. Thus, transcription of three P. falciparum heat shock genes will be analyzed as a model system. Nuclear run on assays will be used to determine the transcription rates of these genes in the absence and presence of heat stress. In vivo reporter assays will be used to determine the promoter sequences required for transcription. Proteins that require transcription of the heat shock genes will be purified by DNA affinity chromatography and identified by mass spectroscopy. These studies will enhance our understanding of transcription in P. falciparum, and allow a better understanding of pathogenesis, differentiation, and drug resistance in this parasite.