ORGANELLE GENOMES OF MALARIAL PARASITES

在疟疾寄生虫中，功能性线粒体和电子传递 蛋白质对寄生虫的生存和生长至关重要。其中一些 抗疟疾药物可能通过抑制体内电子传递发挥作用。 寄生虫，很可能合理的药物设计策略可能会 以这些和其他线粒体功能为目标。在研究遗传学方面 指定疟原虫线粒体基本成分的系统，一些 在过去的几年里，有趣的信息浮出水面。确实有 两个独立的染色体外DNA分子，它们指定细胞器 功能：6kb DNA分子的串联阵列，在此发现 实验室，构成了可能的线粒体基因组，而35kb 环状DNA分子似乎指定了更常见的 叶绿体基因组。为了进一步研究细胞器遗传 系统，这个实验室将(A)表征电子传输 由6kb DNA分子编码的蛋白质；(B)研究两者之间的关系 在6kb和35kb的DNA分子之间；和(C)调查 6kb DNA的转录本和转录机制 基因操作，一种由编码基因组成的混合系统 疟疾寄生虫和细菌的电子传递蛋白将被 被构建为研究抗疟疾药物作用的模型。 6kb和35kb DNA分子的定位和遗传 被研究以确定这些分子可能驻留的细胞器。 最后，我们将研究6kb dna的转录机制： 线粒体RNA聚合酶基因的克隆；通过鉴定DNA- 结合蛋白；并通过研究表达的发育调节 来自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.