Molecular Analysis of PFEMP1 Binding Activity

点击翻译按钮获取中文摘要

DESCRIPTION: (provided by the applicant): It is estimated that Plasmodium falciparumkills one to two million people each year. While most infections are not lethal, severe disease occurs when infected erythrocytes sequester and accumulate in vital organs, such as brain and placenta. The P. falciparumerythrocyte membrane protein 1 (PfEMP1) family has a critical role in infected erythrocyte sequestration. PftMP1 are binding ligands that are exported to the erythrocyte surface. PfEMP1 have different binding specificity and are believed to determine the anatomic distribution of infected erythrocytes and disease outcome. To explore the role of PfEMP1 in malaria pathogenesis we will study three binding traits of infected erythrocytes, adhesion to CD36, to Intercellular adhesion molecule 1 (ICAM-1), and to chondroitin sulfate A (CSA) that have been implicated in malaria disease. CD36 is the major endothelial receptor for parasite sequestration. ICAM-1 and CSA have been implicated in cerebral and placental sequestration, respectively. PfEMP1 binding domains for each of these receptors have been defined. It is estimated that each parasite strain has approximately fifty different PfEMP1. We plan to perform whole genome surveys of PfEMPI binding, with high-throughput assays, focusing on the 3D7 parasite that is the subject of the Malaria Genome Project. Findings from these investigations will assess the extent to which binding properties are encoded and conserved between HEMP 1 in a genome and will provide insight into the pathogenic potential of P. falciparum.