Abstract
Plasmodium falciparum parasites (causing more than 500,000 deaths each year) are transmitted from human to human via gametocytes (i.e. the sexual and only transmissible parasite stages) which are taken up by mosquitoes during a blood meal. A small fraction of parasites convert to gametocytes at every life cycle; nevertheless our understanding of which factors influence this decision and increase parasite conversion to gametocytes is poorly understood. In this project, we aim to investigate whether host and parasite genetics alter gametocyte conversion and if host anti-gametocyte immunity modifies gametocyte carriage (i.e. the gametocytes burden in peripheral blood) . We will use recently developed in vitro conversion assays and establish a novel ex vivo conversion assay, to measure the effect of host and parasite genetics on gametocyte conversion within P. falciparum transgenic lines as well as in field isolates. Furthermore, the potential contribution of host immune responses to the carriage of circulating stage V gametocytes will be assessed with immunological assays. We expect that the outcomes of this project will guide the development of new targets and tools (e.g. drugs and vaccines against the transmissible stages of the parasite) and will provide the knowledge to improve malaria transmission-blocking interventions.
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