Synthetic glycosyl phosphatidyl inositol (GPI) glycolipids as molecular tools to elucidate molecular mechanisms of malaria infection

Synthetic glycosyl phosphatidyl inositol (GPI) glycolipids are powerful synthetic tools to reveal the role of these cell surface molecules in a host of disease states. The focus of this presentation will be on the role of GPI glycans in malaria disease and prion infection. Plasmodium falciparum, the most deadly form of the protozoan parasite that causes malaria, enters human erythrocytes as part of its complex life cycle. We identified a GPI glycan as the malaria toxin. The molecular process that enables merozoites to enter red blood cells is not completely understood and the search for a receptor on host cells continues. We show that glycosyl phosphatidyl inositol (GPI) glycans, present on the apical surface of merozoites, interact with a protein on the surface of the host cell. The protein‐GPI interaction is essential for merozoite entry into erythrocytes and mediates the inflammatory response via human macrophages. Targeting the GPI‐moesin recognition process should enable novel modes of therapeutic intervention and vaccination against malaria.