Joseph D. Smith, Ph.D.
Colorado State University

Genome-wide Binding Analysis of the Plasmodium falciparum Erythrocyte Membrane 1 Family of Cytoadherent Receptors.

The ability of Plasmodium falciparum-infected erythrocytes to bind endothelium and sequester in microvasculature is a key determinant in malaria pathogenesis. Infected erythrocyte cytoadherence is believed to enhance parasite transmission to mosquitoes, but can cause vital organ dysfunction. P. falciparum uses a large family of variant proteins, called P. falicparum erythrocyte membrane 1 (PfEMP1), to cytoadhere. PfEMP1 differ in their binding specificity and are believed to determine the organ-specific pattern of parasite sequestration and disease outcome. Each parasite genome has an estimated 50 different PfEMP1, complicating our understanding of the parasite’s functional capabilities. We are pursuing a whole genome survey of PfEMP1 binding to host receptors implicated in severe disease using sequence information from the Malaria Genome Project. This project identifies, for the first time, a full repertoire of PfEMP1. Coupled with high-throughput binding assays, this approach will assess how binding properties are conserved between PfEMP1 and provide insight into the pathogenic potential of P. falciparum.

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