Niraj H. Tolia, Ph.D.

DEPARTMENT OF Molecular Microbiology
Keywords: host-pathogen, malaria, invasion, crystallography, structural biology, receptor-ligand

Our research group is focused on understanding host-pathogen interactions important for the pathogenesis of disease.

We are interested in the molecular events that occur during erythrocyte invasion by Plasmodium parasites, the etiological agents of malaria. We use the tools of structural biology, biochemistry, cell biology and parasitology to examine proteins and protein complexes associated with these events.

Malaria causes an estimated 300-500 million cases and 1-3 million deaths annually, 80% of which are in children under the age of five. The clinical symptoms of malaria culminate upon red blood cell invasion by Plasmodium parasites, the etiological agents of Malaria. Therefore, preventing binding and invasion of red blood cells is an attractive target for therapeutics (drugs and vaccines).

Attachment of the parasite to a red blood cell requires several interactions mediated by the Erythrocyte-binding like family (EBL). One such interaction occurs between erythrocyte binding antigen 175 (PfEBA-175), a parasite surface protein, and the sugars of glycophorin A (GpA) on the red blood cell. Previously, we have solved the crystal structure of the binding domain of EBA-175 in complex with glycans from GpA. We are in the process of expanding this work to other interactions and events during erythrocyte invasion. A detailed understanding of the interactions is necessary to develop methods to inhibit invasion.

Towards vaccine design, we are interested in understanding the molecular mechanisms of antibody-mediated neutralization. Several antibodies target the parasite EBL-proteins, but only a subset of the antibodies are neutralizing and can block invasion. Our work will determine the epitopes recognized by neutralizing antibodies, and characterize the mechanism of inhibition.