EVOLUTION OF THE NEMATODE INTESTINE, A KEY HOST INTERFACE

线虫肠道的进化，一个关键的宿主接口

• 批准号: 8087733
• 负责人: Makedonka Mitreva
• 金额: $ 25.42万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-15 至 2015-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8087733
• 关键词: Accounting; Adult; Ancylostoma (genus); Animal Feed; Anthelmintics; Ascaris suum; Automobile Driving; Bioinformatics; Biological; Birth; Brugia malayi; Categories; Cells; Cellular biology; Cessation of life; Characteristics; Child; Communities; Complementary DNA; Data; Developing Countries; Development; Diagnostic; Disease; Environment; Evolution; Family member; Foundations; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; Genetic Polymorphism; Genome; Genomics; Goals; Haemonchus; Helminths; Hookworm Infections; Hookworms; Human; Humanities; Immune; Immune system; In Situ; Infection; Intestines; Knowledge; Lead; Life; Medical; Methods; Modeling; Molecular; Molecular Models; Molecular Profiling; Morbidity - disease rate; Necator; Nematoda; Nutrient; Nutritional; Parasite Control; Parasites; Parasitic nematode; Pathogenicity; Personal Satisfaction; Pharmaceutical Preparations; Population; Poverty; Prevention; Productivity; Protein Family; Proteins; Proteome; Research; Resistance; Staging; Strongyloides; Technology; Testing; Therapeutic; Tissues; Trichinella spiralis; Trichuris; Vaccines; base; biological research; cellular targeting; chemotherapy; child physical development; comparative genomics; coping; genetic element; hazard; human morbidity; improved; knowledge of results; molecular modeling; mortality; neglect; next generation; novel; parasitism; pathogen; trait

DESCRIPTION (provided by applicant): More than three billion people, one-half of humanity, are infected with parasitic nematodes. These pathogens are the main causative agents of neglected diseases, causing mortality and morbidity in humans and interfering with normal development in children. Parasitic nematodes reduce productivity of food animals and crops which are critical for economical and nutritional well-being, especially for people in developing countries. The biological and genomic complexity of nematodes has impeded the clarification of principles that could have general application towards advancing parasite control. Our research is intended to resolve this complexity substantially by partitioning it into conserved and diverse genetic elements that have been retained or have evolved throughout the evolution of the Nematoda. Our focus is on the nematode intestine, which is a metabolically active interface with the host and its immune system. While it is a demonstrated target for both immune- and chemo-therapeutic approaches to parasite control, very little is known regarding the conserved and variable features of this interface. Uncovering the evolutionary principles underlying both conserved and adaptable features of the nematode intestine will provide the research community with optimal targets for effective parasite control. The three aims in this proposal focus on providing a comprehensive understanding of genes that are expressed in the adult nematode intestine from parasites that span the evolutionary extremes of the phylum. The intestinal transcriptomes from the selected core species will be used to determine the pan-Nematoda intestinal transcriptome. Advanced bioinformatic approaches will be applied to delineate intestinal genes from all other available nematode genomes, emphasizing human pathogens that are too small to support direct analysis of intestinal functions. Intestinal protein families will be investigated to identify those that have undergone births or deaths and expansions or contractions throughout nematode evolution. Finally, we will determine functional categories of intestinal protein families that reflect adaptable traits of the highest importance in evolution of parasitism. Resulting knowledge is essential to understand molecular features of nematode intestinal cells that facilitate nutrient acquisition in diverse trophic environments, while coping with hazards that accompany exposure at this key interface with the host. In turn, that knowledge will guide strategies to circumvent critical parasite functions by immunological or chemotherapeutic means. PUBLIC HEALTH RELEVANCE: Parasitic nematodes are a major cause of neglected diseases in over half of the world's population, and are a leading cause of human morbidity. The main goal of this project is through implementation of comparative genomics and experimental approaches to advance principles that will have broad application to immune control of parasitic nematodes. This will be accomplished by identifying molecular and cellular features of the nematode intestine that are conserved across the Nematoda or have figured decisively in the adaptive evolution of nematode pathogens. The nematode intestine is demonstrated to be the critical interface with the host; therefore, it is the most versatile tissue for control or prevention. The gained knowledge will focus research on cellular targets with the broadest application to parasite control.

描述（由申请人提供）：超过30亿人，即人类的一半，感染了寄生线虫。这些病原体是被忽视的疾病的主要病原体，造成人类死亡和发病，并干扰儿童的正常发育。寄生线虫降低了食用动物和作物的生产力，而这些动物和作物对经济和营养健康至关重要，特别是对发展中国家的人们。线虫的生物学和基因组的复杂性阻碍了可能对推进寄生虫控制具有普遍应用的原则的澄清。我们的研究旨在通过将其划分为保守和多样的遗传因子来解决这种复杂性，这些遗传因子在线虫的进化过程中一直保留或进化。 我们的重点是线虫的肠道，这是一个代谢活跃的接口与主机和它的免疫系统。虽然它是一个证明目标的免疫和化学治疗方法来控制寄生虫，很少有人知道这个接口的保守和可变的功能。揭示线虫肠道保守和适应性特征的进化原理将为研究界提供有效控制寄生虫的最佳目标。 本提案中的三个目标集中在提供对跨越门的进化极端的寄生虫在成虫线虫肠道中表达的基因的全面理解。来自选定核心种属的肠道转录组将用于确定泛线虫肠道转录组。先进的生物信息学方法将被应用于从所有其他可用的线虫基因组中描绘肠道基因，强调人类病原体太小，无法支持肠道功能的直接分析。肠道蛋白质家族将进行调查，以确定那些经历了出生或死亡和扩张或收缩整个线虫进化。最后，我们将确定肠蛋白家族的功能类别，反映适应性的特点，在寄生虫的进化中的最重要的。 由此产生的知识是必不可少的，以了解线虫肠道细胞的分子特征，促进营养物质的收购在不同的营养环境，同时应对的危害，伴随着暴露在这个关键接口与主机。反过来，这些知识将指导通过免疫或化疗手段规避关键寄生虫功能的策略。 公共卫生相关性：寄生线虫是世界上一半以上人口中被忽视的疾病的主要原因，并且是人类发病的主要原因。该项目的主要目标是通过实施比较基因组学和实验方法来推进将广泛应用于寄生线虫免疫控制的原则。这将通过鉴定线虫肠道的分子和细胞特征来实现，这些特征在线虫纲中是保守的，或者在线虫病原体的适应性进化中起决定性作用。线虫的肠道被证明是与宿主的关键接口，因此，它是最通用的控制或预防组织。所获得的知识将集中在细胞目标的研究与最广泛的应用寄生虫控制。