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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI010645-17
Application #
3564406
Study Section
Tropical Medicine and Parasitology Study Section (TMP)
Project Start
1978-09-29
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
17
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106