Molecular Characterization of Insect Pheromone Chemosensory Mutants in Nematodes

线虫昆虫信息素化学感应突变体的分子表征

• 批准号: 8015243
• 负责人: Ray L Hong
• 金额: $ 14.36万
• 依托单位: CALIFORNIA STATE UNIVERSITY NORTHRIDGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2013-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8015243
• 关键词: Afferent Neurons; Animals; Arthropods; Asians; Behavior; Behavioral; Behavioral Genetics; Brugia malayi; Caenorhabditis elegans; Candidate Disease Gene; Chemicals; Chemotaxis; Communication; Development; Developmental Process; Disease; Engineering; Environment; Evolution; GTP-Binding Proteins; Gene Expression; Genes; Genetic; Genetic Markers; Genetic Screening; Genomics; Human; Insecta; Intercept; Invertebrates; Knowledge; Length; Lesion; Life; Logic; Maps; Mediating; Modeling; Molecular; Molecular Genetics; Mutation; Nematoda; Neurons; Odors; Order Coleoptera; Other Genetics; Output; Parasitic nematode; Partner in relationship; Pathway interactions; Pattern; Perception; Phenotype; Pheromone; Physiology; Postdoctoral Fellow; Proteins; Smell Perception; Soil; Specificity; System; TRP channel; Time; Transgenic Organisms; Translating; Variant; Wing; Work; comparative; gain of function; homeodomain; human disease; improved; molecular marker; mutant; neurophysiology; positional cloning; preference; promoter; public health relevance; receptor; response; vector

DESCRIPTION (provided by applicant): Given the multitude of nematodes associations with invertebrate and vertebrate hosts, the beetle associated Pristionchus pacificus nematode represents a much needed knowledge bridge between the free-living soil nematode Caenorhabditis elegans and many disease causing filarial nematodes such as Brugia malayi and Wucheria bancrofti. While recent advances in insect pheromone recognition were conducted on insects regarding intraspecies interactions, primarily in mating, we know very little about the components needed to mediate interspecies interactions between nematodes and insects, the latter being a significant vector for spreading human diseases. Specifically, how does chemosensation toward a particular compound become reprogrammed during speciation, and how much does this influence the nematodes' host preferences? Aside from C. elegans, P. pacificus is the only other nematode in which a forward genetic approach is feasible. We have therefore carried out the first behavioral genetic screen in P. pacificus for lack of chemotaxis toward a known oriental beetle pheromone, ZTDO, and isolated two Oriental Beetle pheromone Insensitive mutants: obi-1 and obi-3. Obi-1 and obi-3 are specifically unable to chemotaxis toward ZTDO but are wildtype in chemotaxis toward other attractants. We will identify the molecular lesions of obi-1 and obi-3 and mis-express the P. pacificus wildtype genes using C. elegans winged amphid neuron promoters such as odr-7 and str-2 (specific for AWA and AWC, respectively) and look for gain-of-function attraction chemotaxis phenotype towards ZTDO in C. elegans. Thus we will attempt to engineer a new chemosensory output into C. elegans and thereby determine the genes required for reprogramming chemosensory behavior. The molecular mechanisms for how human parasitic nematodes sense their host environments has largely been extrapolated from the free-living C. elegans, but may be more closely modeled by the arthropod associated P. pacificus that senses insect host pheromones. This proposal outlines the first olfaction behavioral screen in P. pacificus and aims to understand the specific developmental and neurophysiological factors mediating Pristionchus attraction to a pheromone using a combination of molecular and genetic approaches. PUBLIC HEALTH RELEVANCE: The molecular physiology of insect pheromone attraction will have a direct impact on our understanding of olfaction in nematodes, as well as chemosensation in general. Our proposal has the potential to be translated into improving treatments against parasitic nematodes by targeting their means of perceiving their environment and to elucidate the overall diversity of molecular pathways in animal chemosensation.

描述（由申请人提供）：考虑到线虫与无脊椎动物和脊椎动物宿主的多种关联，甲虫相关的太平洋棱纹线虫代表了自由生活的土壤线虫秀丽隐杆线虫与许多引起疾病的丝虫线虫如马来丝虫和班氏吴氏线虫之间急需的知识桥梁。虽然昆虫信息素识别的最新进展是在昆虫种内相互作用方面进行的，主要是在交配中，但我们对介导线虫和昆虫之间种间相互作用所需的组分知之甚少，后者是传播人类疾病的重要载体。具体来说，在物种形成过程中，对特定化合物的化学感觉是如何被重新编程的，这对线虫的宿主偏好有多大影响？除了C。pacificus是唯一一种正向遗传方法可行的其他线虫。因此，我们进行了第一次行为遗传筛选太平洋拟步行虫缺乏对已知的东方甲虫信息素，ZTDO的趋化性，并分离出两个东方甲虫信息素不敏感突变体：obi-1和obi-3。Obi-1和obi-3特异性地不能对ZTDO进行趋化，但对其他引诱物具有趋化性。我们将鉴定obi-1和obi-3的分子病变，并使用C. elegans有翅两栖类神经元启动子如odr-7和str-2（分别对AWA和AWC特异），并在C.优美的因此，我们将尝试将一种新的化学感受输出工程化到C。从而确定重编程化学感受行为所需的基因。人类寄生线虫感知宿主环境的分子机制主要是从自由生活的C。elegans，但可能更接近模仿节肢动物相关的P. pacificus，感觉昆虫宿主信息素。该提案概述了第一个嗅觉行为屏幕在太平洋拟步行虫，并旨在了解特定的发育和神经生理因素介导的Pristionchus吸引信息素的分子和遗传方法相结合。 公共卫生相关性：昆虫信息素吸引的分子生理学将对我们理解线虫的嗅觉以及一般的化学感觉产生直接影响。我们的建议有可能被转化为改善治疗寄生线虫通过针对他们的手段感知他们的环境，并阐明动物化学感受的分子途径的整体多样性。