Transcriptional Regulation in Plasmodium falciparum

Harvard University (Sch Of Public Hlth), Boston MA

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Abstract

DESCRIPTION (provided by the applicant): Human malaria results from infection by the protozoan parasite Plasmodium sp. Currently, 300-500 million peoples are infected with malaria, and 1.5-3.5 million individuals succumb annually to the disease. Although expression of many P. falciparum genes involved in pathogenesis and development are regulated at the level of transcription, there is little mechanistic information regarding transcription in these organisms. Thus, transcription of three P. falciparum heat shock genes will be analyzed as a model system. Nuclear run on assays will be used to determine the transcription rates of these genes in the absence and presence of heat stress. In vivo reporter assays will be used to determine the promoter sequences required for transcription. Proteins that require transcription of the heat shock genes will be purified by DNA affinity chromatography and identified by mass spectroscopy. These studies will enhance our understanding of transcription in P. falciparum, and allow a better understanding of pathogenesis, differentiation, and drug resistance in this parasite.