The overall objectives of this research proposal are to study, by electron microscopy, 1) the composition of the junctions formed between the P. falciparum merozoite and erythrocyte membrane during merozoite invasion, 2) the formation of knobs on erythrocytes infected by P. falciparum or P. malariae, 3) the role of erythrocyte cytoskeleton in malaria and 4) the mode of action of cyclosporin A on the erythrocytic stages of P. falciparum. Immuno-electron microscopy using various monoclonals, protein-A gold and cryoultramicrotomy or LR White resin, will identify proteins and cytoskeleton which are associated with junctions formed between merozoites and erythrocyte membranes. The characterization of these junctions may reveal new approaches for inhibiting their formation, thereby helping to prevent malaria infection. Studies of knob formation and composition will give clues on how to inhibit their formation. This information may be helpful for preventing some complications of falciparum malaria, such as cerebral malaria. The understanding of the mode of action of cyclosporin A on the erythrocytic stages of P. falciparum will contribute to the advancement of our knowledge on the treatment of malaria. Thus, investigations proposed here should provide answers to a number of basic questions on host-parasite interaction and may lead to the discovery of better methods for the control of malaria.
