Malaria Erythrocyte Binding-like Genes & Host Specificity in a Natural Population

描述(申请人提供)：疟疾每年造成多达270万人死亡。在这里，我们计划研究自然鸟类群体中疟疾寄生虫宿主特异性的分子基础。我们以前的数据显示，某些品系的疟原虫。完全是宿主特有的；它们感染一种雀形目鸟类，但不感染同一科的另一种鸟。另一些病毒感染了许多种类的鸟类。我们建议确定一个蛋白质家族，即红细胞结合样蛋白(EBL)，在自然发生的鸟类种群中如何变化。其他人的工作表明，EBA-175区域II区域的差异可以解释恶性疟原虫和雷氏疟原虫之间的宿主特异性，这两种寄生虫分别感染人类和黑猩猩。我们打算测试这些基因在宿主特异性明显的自然种群中的变化。在这项研究中，鸟类种群为疟疾研究提供了一个很好的模式系统，因为它们不受人类文化和社会经济模式的影响。利用基因组学的互补技术、建立的基于聚合酶链式反应的检测方法和分子系统发育学方法，我们从鸡寄生虫中鉴定出一个候选的EBL基因。有了这些信息，我们将从自然鸟类种群中分离出同源基因，目的是弄清寄主专一性如何解释寄生虫病的分布。我们将致力于这三个特定的目标：1.鸡疟原虫红细胞结合样(EBL)基因家族的特征。2.分离疟原虫EBL家族的同源基因。发现于非洲热带雨林鸟类中。3.测定感染热带雨林鸟类的寄生虫自然种群中EBL结合域的变异，并将遗传多样性与宿主特异性联系起来。该提案还概述了在凯斯西储大学彼得·齐默尔曼博士的指导下，国际和平研究所的发展。这项研究是一系列调查的第一步，这一系列调查将构成PI长期研究计划的基础，因此是他职业发展计划的重要组成部分。 公共卫生相关性：在这里，我们建议研究在自然鸟类种群中赋予疟疾宿主特异性的基因。这一结果将有助于更好地理解疟疾中的宿主转换以及对未来宿主转换事件的预测。一旦我们确定了影响宿主特异性的基本遗传因素，我们就能够预测宿主转换的发生，从而更好地理解疟疾是一种新出现的疾病。

DESCRIPTION (provided by applicant): Malaria causes up to 2.7 million human deaths per year. Here we plan to study the molecular basis of the host-specificity of malaria parasites in a natural population of birds. Our previous data has shown that certain strains of Plasmodium spp. are entirely host specific; they infect one species of passerine bird, but not another in the same family. Others infect many species of birds. We propose to determine how one family of proteins, the erythrocyte binding-like (EBL) proteins, varies in naturally occurring populations of birds. Work by others has shown that differences in the region II domain of EBA-175 can account for host-specificity between P. falciparum and P. reichenowi, parasites that infect humans and chimpanzees respectively. We intend to test how these genes vary in a natural population where host-specificity is apparent. In this study, bird populations provide an excellent model system for the study of malaria since they are not subject to human cultural and socio-economic patterns. Using complementary techniques of genomics, established PCR-based detection methods, and molecular phylogenetics, we have identified a candidate EBL gene from P. gallinaceum, a parasite of chickens. With this information, we shall isolate orthologous genes from natural populations of birds, with the intent to discern how host specificity accounts for the distribution of parasitic diseases. We will address these three specific objectives: 1. Characterize the erythrocyte binding-like (EBL) family of genes in Plasmodium gallinaceum of chickens. 2. Isolate orthologous genes to the EBL family in Plasmodium spp. found in African rainforest birds. 3. Determine the variation in EBL binding domains in natural populations of parasites infecting rainforest birds, and correlate genetic diversity with host-specificity. The proposal also outlines the development of the PI through the mentorship of Dr. Peter Zimmerman of Case Western Reserve University. This study is the first step in a line of inquiry that will form the basis of the PI's long-range research program and thus is an essential component of his career development plan. PUBLIC HEALTH RELEVANCE: Here we propose to study genes that confer the host specificity of malaria in a natural population of birds. The results will aid in the better understanding of host-switching in malaria and the prediction of future host switching events. Once we ascertain basic genetic factors that contribute to host-specificity, we shall be able to predict the occurrence of host switching and thus better understand malaria as an emerging disease.