Studying the effects of immune cell-secreted peptides on malaria sexual stages

The purpose of the visit to the lab of Assoc. Prof. Noushin Emami is to test the biological activity of peptides secreted by the immune system on the sexual and mosquito-resident stages of the malaria parasite (Plasmodium falciparum). The life cycle of the malaria parasite is complex and alternates between its human host and the mosquito vector. The most important process in the transmission of malaria is the development of the sexual stages of the parasite (gametocytes), which starts in the human host and culminates in the mosquito vector, where the sexual stages mature and invade the mosquito. Gametocytes are an extremely crucial stage in the life cycle of the parasite, since blocking their generation could potentially lead to blocking the transmission of malaria. However, the experimental tools to study the sexual stages of malaria are still limited and challenging, since they involve using mosquito vectors. In Israel, culturing mosquito stages of the malaria parasite is not allowed, given the geographic potential for accidental disease spread. Assoc. Prof. Noushin Emami and her lab are experts in gametocytes and culturing the sexual stages of malaria in mosquito vectors; therefore, in order to study this crucial aspect of malaria biology, an application for this fellowship was made. The overall experimental approach involves isolating and purifying immune cell-derived small peptides after stimulation with Pf at the Weizmann Institute, Israel. Numerous studies have reported that immune cells secrete small peptides that can serve as communication tools to boost immunity or directly kill pathogens, such as the well-known antimicrobial peptides (AMPs). Selected peptides with no infectious or biohazardous potential will be shipped to Assoc. Prof. Emami’s laboratory at the University of Greenwich, where technical ability will be acquired to perform functional assays on gametocytes and mosquito stages of the malaria parasites after treatment with the peptides. The proposed assays to perform include, but are not limited to, classical in vitro gametocyte culture in human blood, gamete exflagellation assay, and oocyst formation in infected mosquitoes. These assays will provide an integral overview of the possible effects of the peptides in numerous stages of the sexual development of the malaria parasite. With this visit, it is intended to gain new knowledge on how peptides secreted by the immune system can affect the sexual stages of malaria. Importantly, since AMPs have been reported to be effective at killing malaria parasites, very valuable information regarding their activity on sexual stages, which are nearly impossible to study in Israel, will be obtained. Some of these peptides could even become druggable candidates that could either stop the sexual differentiation in the human host or be used to prevent the development of the parasite within its mosquito vector.

External Reference Name

Basic Science

Mar 2024 — Apr 2024

$4,914

United Kingdom