Protein Synthesis And Developmental Transitions In Plasm

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Abstract

We have shown that the amino terminus of the circumsporozoite protein of Plasmodium falciparum plays a crucial functional role in the pathogenesis of malaria involving sporozoite attachment and invasion of liver cells. The amino terminus is not immunogenic when presented as part of the complete protein but highly immunogenic when presented as a separate peptide. We suggest that hiding functional moieties of the protein from the immune system is an evasion strategy to preserve liver cell binding function and may be of importance in designing anti-sporozoite vaccines. We have also studied the biochemistry of sexual development in Plasmodium. During transmission of P. falciparum from human to mosquito vector, the parasite encounters a temperature change which correlates with the onset of the parasite's sexual cycle. We have shown that the parasite has sensors to monitor the environment and, in response, effect developmental change. The transcription of a selective subset of messenger RNAs is up-regulated during the temperature drop. We have described cold-sensitive promoters in the Plasmodium genome which control this expression. We have shown that these can be switched on and off in culture with little if any effect on the parasite and hence have great potential for understanding the biochemistry of the parasite.