Protein export by the malaria parasite. (360G-Wellcome-091095_Z_10_Z)

In low income countries malaria is a leading cause of death, disproportionately effecting children [1]. Plasmodium, a unicellular eukaryote, causes Malaria and is transmitted to humans via mosquito bites. Symptoms of the disease occur when the parasite enters the bloodstream, where it invades and replicates inside erythrocytes. Within the erythrocyte, Plasmodium resides in a membrane-bounded vacuole, the parasitophorous vacuole (PV). By exporting soluble and membrane proteins across the parasito phorous vacuole membrane, into the cytoplasm and to the surface of the infected erythrocyte, the parasite alters the solute permeability, cytoskeleton, and adhesion properties of its host cell. Many exported proteins are required for immune evasion and parasite viability, making them excellent drug targets. Likewise components of the export machinery itself may also represent novel drug targets. The localization of some exported proteins to the surface of the infected erythrocyte makes them exce llent vaccine candidates. Despite the importance of exported proteins to our understanding and potential treatment of malaria, how proteins are exported across the PV membrane is poorly understood. The goal of this proposal is to gain a mechanistic understanding at the molecular level of how soluble proteins are recognized by the export machinery and subsequently exported across the PV membrane.