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.
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