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 currently studying the molecular events that occur during erythrocyte invasion by Plasmodium parasites, the etiological agents of malaria. We use the tools of structural biology, biochemistry and molecular biology 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. After an infection (via a mosquito bite) the parasite invades red blood cells, which is a critical step in the pathogenesis of the disease. Therefore, preventing binding and invasion of red blood cells is an attractive target for therapeutics.

Binding of the parasite to the red blood cells requires several interactions. One of which is the interaction between erythrocyte binding antigen 175 (EBA-175), a protein on the surface of the parasite, 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 that contains the essential components of GpA. This structure allowed us to propose a model for the EBA-175/GpA interaction.

We are in the process of expanding this work to other interactions and events during erythrocyte invasion. Together, our work may have implications for the design of novel interventions for the disease.