Regulation of gene expression in Plasmodium

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DESCRIPTION (provided by the applicant): Plasmodium falciparum causes the most virulent of human malarias. The blood stage parasites comprise of morphologically distinct ring, trophozoite and schizont stages with distinct patterns of gene expression. For instance, the surface adhesion var genes (that have attracted particular interest for their role in pathogenesis) show promiscuous transcription in rings but restricted expression in trophozoites. However whether gene expression is regulated at the level of transcription, message stability and mediated by sequence elements in the UTRs is poorly understood for both VARs and other plasmodial genes. The long-term goals of this project are to understand mechanisms of stage specific gene regulation in Plasmodium falciparum. The study will contribute to our basic understanding of lower eukaryotic gene expression and the regulation of genes such as vars that play an important role in disease pathology. Molecular, genetic tools including transfection to express promoter fusions, combined with biochemical subcellular fractionation assays, will be used to identify elements of gene regulation. Unique mechanisms in var regulation may provide targets against cerebral malaria.