Malaria sporozoites are motile, and exhibit """"""""gliding motility"""""""", a type of protist locomotion that has never been well understood. Data from previous studies suggest that sporozoite motility is necessary for successful sporozoite invasion of host cells. Furthermore, monoclonal antibodies that recognize the immunodominant epitope of the circumsporozoite (CS) protein on the surface of sporozoites inhibit sporozoite motility and invasiveness. This suggests that the CS protein may play a functional role in sporozoite motility, and supports the hypothesis that anti-sporozoite humoral immunity in vivo may function by abolishing sporozoite motility. In view of the current interest in immunizing humans with chemically-synthesized and recombinant CS protein epitopes as a prophylactic measure against malaria, it is an appropriate time to study the cell biology of sporozoite motility and how it relates to successful parasite invasion into target host cells. Sporozoites have a number of structural components that could function in their motility: elements of the parasite cytoskeleton: rhoptries, which store and secrete substances from the sporozoites' anterior end; and the CS protein, which coats the entire external surface. Accordingly, the proposed study aims (1) to further demonstrate the importance of sporozoite motility in invasion, (2) to determine how the CS protein and elements of the sporozoite cytoskeleton and the rhoptry-microneme complex participate in sporozoite motility and invasion, and (3) to investigate the interaction between P. berghei sporozoites and cultured host cells during invasion. Studies aimed at elucidating the mechanism of sporozoite motility and its relationship to successful sporozoite invasion of host cells include (1) a descriptive and immunocytochemical analysis of cytoskeletal actin, (2) inhibiting sporozoite invasion using inhibitors and effectors of sporozoite motility, (3) a dynamic analysis of the sporozoite surface during motility, (4) a study of rhoptry components, with particular regard to the dynamics of secretion and the association of the CS protein, and (5) dynamic and ultrastructural analyses of host cell-sporozoite interactions in vitro.
