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

疟疾红细胞结合样基因

• 批准号: 7940828
• 负责人: Ravinder Nath Marius Sehgal
• 金额: $ 15.2万
• 依托单位: SAN FRANCISCO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7940828
• 关键词: Accounting; Address; Affect; Africa; African; Avian Malaria; Binding; Biological Models; Birds; Blood specimen; Cessation of life; Chickens; Data; Detection; Development; Development Plans; Disease; Ecology; Erythrocytes; Event; Extracellular Domain; Family; Future; Gene Family; Genes; Genetic; Genetic Variation; Genomics; Goals; Human; Knowledge; Laboratories; Lead; Malaria; Mentors; Mentorship; Methodology; Methods; Molecular; Molecular Biology; Motivation; Olives - dietary; Orthologous Gene; Pan Genus; Parasites; Parasitic Diseases; Pattern; Phylogenetic Analysis; Plasmodium; Plasmodium falciparum; Plasmodium gallinaceum; Population; Postdoctoral Fellow; Principal Investigator; Protein Family; Proteins; Research; Research Personnel; Specificity; Students; Techniques; Testing; Underrepresented Minority; United States; Universities; Variant; Work; antigen binding; base; career development; experience; extracellular; novel; programs; public health relevance; skills; socioeconomics; transmission process

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.

描述（由申请人提供）：疟疾每年造成多达270万人死亡。在这里，我们计划研究疟疾寄生虫在鸟类自然种群中的宿主特异性的分子基础。我们以前的数据表明，某些疟原虫菌株完全是宿主特异性的；它们会感染一种雀形目鸟类，但不会感染同一科的其他雀形目鸟类。其他的感染多种鸟类。我们建议确定一个蛋白质家族，红细胞结合样（EBL）蛋白，在自然发生的鸟类种群中是如何变化的。其他人的研究表明，EBA-175 II区结构域的差异可以解释恶性疟原虫和雷氏疟原虫（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在宿主特异性明显的自然种群中如何变化。在本研究中，鸟类种群不受人类文化和社会经济模式的影响，因此为研究疟疾提供了一个很好的模型系统。利用基因组学的互补技术，建立了基于pcr的检测方法和分子系统遗传学，我们从鸡的寄生虫P. gallinaceum中鉴定了一个候选EBL基因。有了这些信息，我们将从鸟类的自然种群中分离出同源基因，目的是辨别宿主特异性如何解释寄生虫病的分布。我们将解决以下三个具体目标：鸡鸡疟原虫红细胞结合样（EBL）家族基因的研究。2. 分离出非洲热带雨林鸟类中疟原虫EBL家族的同源基因。3. 确定感染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的彼得·齐默尔曼博士的指导下，PI的发展。这项研究是一系列调查的第一步，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。