ORGANELLE GENOMES OF MALARIAL PARASITES

在疟疾寄生虫中，功能性线粒体和电子传递 蛋白质对于寄生虫的存活和生长至关重要。一些 抗疟药物可能通过抑制电子传递起作用， 寄生虫，合理的药物设计策略可能 靶向这些和其他线粒体功能。 在研究遗传 系统，指定疟原虫线粒体的基本组成部分，一些 在过去的几年里，一些有趣的信息浮出水面。 有 两个独立的染色体外DNA分子， 功能：6 kb DNA分子的串联阵列，发现于此 实验室，构成了可能的线粒体基因组，而一个35 kb的 环状DNA分子似乎指定了更常见于 叶绿体基因组为了进一步描述细胞器的遗传特性， 系统，该实验室将（a）表征电子传输 由6 kb DNA分子编码的蛋白质;（B）研究 在6kb和35kb DNA分子之间;和（c）研究 转录本和转录机器特异性的6 kb DNA通过 基因操作，一种由基因编码组成的混合系统， 疟疾寄生虫和细菌的电子传递蛋白将被 构建作为研究抗疟药物作用的模型。 6kb和35kb DNA分子的定位和遗传将 研究以确定这些分子可能存在的细胞器。 最后，将研究6 kb DNA的转录机制： 线粒体RNA聚合酶基因的克隆;通过表征DNA- 结合蛋白;并通过研究表达的发育调节 从6kb的DNA分子。

In malarial parasites, functional mitochondria and electron transport proteins are critical for parasite survival and growth. Some of the antimalarial drugs may act through inhibition of electron transport in parasites, and it is likely that strategies for rational drug design could target these and other mitochondrial functions. In studying genetic systems that specify essential components of Plasmodium mitochondria, some intriguing information has surfaced during the last few years. There are two separate extrachromosomal DNA molecules that specify organelle functions: tandem arrays of 6 kb DNA molecules, discovered in this laboratory, constitute the likely mitochondrial genome, whereas a 35 kb circular DNA molecule appears to specify functions more common for chloroplast genomes. To further characterize the organelle genetic systems, this laboratory will (a) characterize the electron transport proteins encoded by the 6 kb DNA molecule; (b) study the relationship between the 6 kb and the 35 kb DNA molecules; and (c) investigate transcripts and transcription machinery specific for the 6 kb DNA Through genetic manipulation, a hybrid system consisting of genes encoding electron transport proteins of malarial parasites and bacteria will be constructed to serve as a model for studying antimalarial drug action. Location and genetic inheritance of the 6 kb and 35 kb DNA molecules will be studied to identify the organelle in which these molecules may reside. Finally, transcription machinery for the 6 kb DNA will be investigated: by cloning of the mitochondrial RNA polymerase gene; by characterizing DNA- binding proteins; and by studying developmental regulation of expression from the 6 kb DNA molecule.