Malaria is a global health problem. The disease is caused by parasites from the genus Plasmodium and is endemic to more than 90 countries. In 2016, 216 million infections and 445,000 deaths were estimated. The parasite is transmitted by female Anopheles mosquitoes during a blood meal. The infectious parasite stage injected by the mosquito is the complex developmental result of parasites taken up approximately three weeks earlier by the same mosquito. Antimalarial drugs efficiently eliminate parasite forms that cause the disease. Gametocytes, the parasite stage taken up by the mosquito, on the other hand, are cleared inefficiently, remain infectious and perpetuate malaria transmission. Intervention strategies that target and block the transmission of gametocytes is part of the malaria elimination strategy, but it is in need of a better understanding of the molecular mechanisms that allow and maximize parasite survival in the mosquito following transmission. Here we will elucidate an essential gene expression strategy employed by the parasite to ensure rapid adaptation and infection of the mosquito vector by the newly formed ookinete. The female gametocyte supplies the developing ookinete with hundreds of messenger RNA templates for rapid protein translation. Using the rodent malaria model Plasmodium berghei we will establish the developmental proteome of ookinete formation providing proteomic snapshots and identifying when such mRNAs are translated; secondly we will define the specific roles of specific RNA binding proteins in the translational control process; and establish new RNA methodologies that will allow the accurate study of mRNA-specific complexes. The overall aim is to understand the underlying molecular mechanisms that define the ordered and timely protein translation needed for ookinete formation. Our work will provide a comprehensive view of translational control during malaria parasite transmission to the mosquito. The methodological innovations of this project will funnel into research on the human-infectious parasite form and the study of related apicomplexan parasites. The findings of this research will spur the development of new intervention strategies that target this key mechanism for parasite infectivity.
Malaria is a major health problem that is aggravated by emerging drug resistance and the lack of an efficient vaccine. In 2016 the disease caused an estimated 216 million clinical cases and more than 445,000 deaths, mostly children under the age of five. This project will provide an understanding of the Plasmodium parasite?s biology and its ability to adapt, survive and infect the mosquito vector, thus identifying key targets for more efficient intervention strategies that block transmission.
