Molecular Analysis of PFEMP1 Binding Activity

描述：（由申请人提供）：估计疟原虫 恶性疟每年导致一到两百万人死亡。虽然大多数感染是 不致命，当受感染的红细胞隔离并发生严重疾病时会发生 积聚在重要器官中，例如大脑和胎盘。 P。 恶性红细胞膜蛋白 1 (PfEMP1) 家族在 感染的红细胞隔离。 PftMP1 是结合配体 输出至红细胞表面。 PfEMP1具有不同的结合特异性 并被认为可以确定感染者的解剖分布 红细胞和疾病结果。 为了探索 PfEMP1 在疟疾发病机制中的作用，我们将研究三个 受感染红细胞的结合特征、与 CD36 的粘附、与细胞间质的粘附 粘附分子 1 (ICAM-1) 和硫酸软骨素 A (CSA) 与疟疾疾病有关。 CD36 是主要的内皮受体 寄生虫隔离。 ICAM-1 和 CSA 与大脑和 分别是胎盘隔离。其中每个的 PfEMP1 结合域 受体已被定义。据估计，每种寄生虫菌株都有 大约五十种不同的 PfEMP1。我们计划进行全基因组调查 PfEMPI 结合，通过高通量测定，重点关注 3D7 寄生虫 这是疟疾基因组计划的主题。从这些结果中得出的结论 调查将评估结合特性的编码程度 并在基因组中的 HEMP 1 之间保守，并将提供对 恶性疟原虫的致病潜力。

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.