We have defined the pattern of transcription of the developmentally regulated rRNA genes of Plasmodium species. We have found that upregulation of one of the genes relates to the differentiation of the sporozoite as a unit within the oocyst. We have also discovered a previously undescribed rDNA unit that is expressed only during oocyst development in the mosquito abdomen, but never carried to the thorax in mature sporozoites. Molecular modeling of the oocyst gene reveals that it would suppress UGA termination; hence, its presence in the translation apparatus would result in fundamental changes in the pattern of translation products that occur during development. We consider the elucidation of the characteristics of this switch of importance with regard to understanding translational control in the parasite. To more directly study the ribosomal rRNAs, we have studied the susceptibility of parasites to both cytoplasmic and organellular ribosome inhibitory drugs. We have shown characteristically different effects of the drugs. We have also produced resistant mutants to one of the cytoplasmic ribosome inhibitors, anisomycin. In separate studies, we have continued our work with attenuated lines of human and rodent malarias. Auxotrophic lines of parasites have been cloned and their developmental characteristics studied. Auxotrophic mutants of both species of parasite have been defined by their dependency on either exogenous pyrimidines or para-aminobenzoic acid. These should prove useful in the study of both the biochemistry of parasites and the development of immunity to parasites.
Showing the most recent 10 out of 29 publications
