New Scholar Award in Global Infectious Disease
Ali A. Sultan, M.D., Ph.D.
Harvard School of Public Health

Molecular Mechanisms of Plasmodium Sporozoite Pathogenicity

Malaria infection is initiated when Plasmodium sporozoites, which are injected by Anopheles mosquitoes, invade hepatocytes of the vertebrate host. The speed and selectivity of hepatocyte invasion indicate the involvement of specific parasite-encoded surface protein(s) and host molecule(s). In addition, Plasmodium sporozoites have the unique ability to glide rapidly on solid substrates, a feature that may facilitate the parasite’s movement and access to target cells. Previously we have provided genetic evidence that the type I transmembrane protein, thrombospondin-related adhesive protein (TRAP), is required both for motility and cell invasion by Plasmodium sporozoites.

Study of the malarial sporozoite biology provides a unique opportunity to identify candidate virulence factors that contribute to the successful transmission of Plasmodium. The developmentally up-regulated sporozoite genes (UIS) recently identified are important stepping stones for the dissection of the molecular mechanisms underlying sporozoite maturation and infectivity to the vertebrate host. The objective of this proposal is to apply biochemical, cell biological and genetic approaches to elucidate the functional role of TRAP in host cell invasion by Plasmodium sporozoites. In addition, we will investigate the role of UIS molecules in sporozoite invasion and their interaction with TRAP.

Results from this study are expected to contribute significantly to our understanding of the molecular and cellular mechanisms mediating interaction between Plasmodium and host cells. The experiments described here could provide the basis for new vaccine candidates and drug therapies.

Contact Dr. Sultan.