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.
