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

描述（由申请人提供）：疟疾每年导致多达270万人死亡。在这里，我们计划研究疟疾寄生虫在鸟类自然种群的宿主特异性的分子基础。我们以前的数据表明，某些疟原虫株。完全是宿主特异性的;它们感染雀形目鸟类的一种，但不感染同一家族的另一种。其他的则感染了许多种类的鸟类。我们建议，以确定如何一个家庭的蛋白质，红细胞结合样（EBL）蛋白，在自然发生的鸟类种群的变化。其他人的工作表明，EBA-175的区域II结构域的差异可以解释恶性疟原虫和赖氏疟原虫（分别感染人类和黑猩猩的寄生虫）之间的宿主特异性。我们打算测试这些基因如何在宿主特异性明显的自然人群中变化。在这项研究中，鸟类种群为疟疾研究提供了一个很好的模型系统，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，建立了基于PCR的检测方法，和分子生物学，我们已经确定了一个候选EBL基因从鸡的寄生虫P. gallinaceum，一个寄生虫。有了这些信息，我们将从鸟类的自然种群中分离出直向基因，目的是了解宿主特异性如何解释寄生虫病的分布。我们将实现这三个具体目标：1。描述鸡疟原虫红细胞结合样基因家族的特征。2.分离疟原虫属中EBL家族的直向同源基因。发现于非洲雨林鸟类中。3.确定感染雨林鸟类的寄生虫自然种群中EBL结合域的变化，并将遗传多样性与宿主特异性相关联。该提案还概述了通过凯斯西储大学的彼得齐默尔曼博士的指导发展PI。这项研究是调查的第一步，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，我们建议研究基因，赋予疟疾的宿主特异性在自然种群的鸟类。这些结果将有助于更好地了解疟疾的宿主转换和预测未来的宿主转换事件。一旦我们确定了有助于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，从而更好地了解疟疾这一新出现的疾病。

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.