Presentation description

Malaria is a life-threatening infectious disease prevalent in sub-Saharan Africa that remains an important global health burden, primarily affecting children under five. Plasmodium falciparum parasites cause severe malaria and have adapted in response to humans evolving. An evolutionary arms race occurs when two organisms in a host-pathogen relationship continually adapt to outcompete each other. In the arms race between humans and Plasmodium parasites, the sickle cell trait, which involves a mutation in human hemoglobin, has historically protected against severe malaria. However, recent genomic studies have identified Plasmodium falciparum sickle-associated (Pfsa) alleles that may allow the parasite to overcome this protection. Our study aims to understand the localization and functions of Pfsa2 and Pfsa3 proteins. Although these alleles may enhance parasite fitness in HbS-containing erythrocytes, the encoded protein function remains largely unknown. We hypothesize that changes in Pfsa2 and Pfsa3 prevent the normal export of these proteins into the erythrocyte of wild-type (WT) parasites, leading to protein retention within the Pfsa parasite and potentially contributing to their survival in sickle-trait blood. To test this hypothesis, we are generating WT and Pfsa overexpression plasmids for Pfsa2 and Pfsa3 and transfecting them into WT parasites. We will use western blot analysis to validate protein expression, followed by immunofluorescence assays to determine the subcellular localization of the encoded proteins. Deciphering how these alleles allow parasite survival in sickle trait blood may reveal novel therapeutic targets for sickle cell disease and strengthen our understanding of the evolutionary arms race that shapes human and parasite survival.