Genetic Analysis of C. elegans Predator Avoidance

线虫捕食者回避的遗传分析

• 批准号: 8681539
• 负责人: Sreekanth H. Chalasani
• 金额: $ 48.5万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681539
• 关键词: Affect; Afferent Neurons; Agar; Animals; Anxiety; Automobile Driving; Behavior; Behavioral; Behavioral Assay; Behavioral Genetics; Biological Models; Biological Neural Networks; Bite; Blood Circulation; Brain; CREB1 gene; Caenorhabditis elegans; Cardiovascular system; Cells; Claw; Code; Complex; Developmental Biology; Disease; Eating; Ensure; Environment; Exposure to; Feeds; Genes; Genetic; Genetic Models; Genetic Screening; Glutamate Transporter; Glutamates; Goals; Hour; Human; Institutes; Insulin; Invertebrates; Knowledge; Left; Locomotion; Measures; Methods; Mitochondria; Modeling; Molecular; Muscle; Nature; Nematoda; Nervous system structure; Neuroanatomy; Neurobiology; Neurons; Neurotransmitter Receptor; Neurotransmitters; Organism; Output; Physiological; Physiology; Process; Puncture procedure; Recurrence; Research; Role; Serotonin; Side; Signal Pathway; Signal Transduction; Signaling Molecule; Stress; Synapses; System; TRPV channel; Therapeutic Intervention; Tooth structure; Whole Organism; avoidance behavior; biological adaptation to stress; cellular targeting; enzyme biosynthesis; gastrointestinal system; genetic analysis; high throughput screening; imaging modality; information processing; insight; interest; mutant; neural circuit; neuromechanism; novel; novel diagnostics; programs; public health relevance; response; serotonin transporter; stressor; tool; uptake

DESCRIPTION (provided by applicant): All organisms possess an intrinsic ability to detect and respond to threats in their environments, but the underlying molecular mechanisms are poorly understood. A complete understanding of this process requires knowledge of the underlying neural circuits along with an ability to measure and, most importantly, perturb their activity. This is difficult to obtain in complex vertebrate circuits. However, invertebrate circuit with their well-defined neuroanatomy and quantitative behaviors are ideally placed to decipher the underlying machinery guiding complex outputs. This proposal aims to understand the neural mechanisms that code threat responses (both behavioral and physiological) in an invertebrate brain model. The nematode, Caenorhabditis elegans, provides a unique opportunity to analyze, using a multi- scale approach, genes, cells and circuits that regulate complex behaviors. The Chalasani lab has developed a novel model of threat behaviors using the interactions between C. elegans and a second nematode, Pristionchus pacificus. A starving Pristionchus will attack and devour C. elegans in 30 minutes. C. elegans in turn, will avoid both Pristionchus and its secretions. Apart from this behavioral response, C. elegans also activates mitochondrial stress upon exposure to Pristionchus. The goals of the proposed research program are to define the cellular and molecular mechanisms regulating avoidance behavior in this model system. It has already been determined that a novel neural circuit including three new sensory neurons (ASJ, ASK and ASI) drive avoidance behavior and physiological stress responses. Specific aim 1 will identify this neuronal circuit and the associated neurotransmitters and receptors that regulate predator avoidance and mitochondrial stress responses. Aim 2 will optimize an automated behavioral platform to rapidly analyze behaviors from large numbers of worms and perform a large screen for genes affecting avoidance behavior. A pilot screen has identified 4 interesting genes as required for regulating avoidance behavior. These include a TRPV channel (might be part of the Pristionchus sensing machinery), glutamate transporters and serotonin biosynthesis enzyme and serotonin re-uptake transporter. Aim 3 is focused on validating these and other candidates from the genetic screen. These studies will clarify how neural circuits process information about environmental threats at the level of synapses, neural circuits and whole organisms. Moreover, we will identify basic principles and conserved mechanisms of how neural circuits integrate glutamate and serotonin signaling to generate complex behaviors.

描述（由申请人提供）：所有生物体都具有检测和应对其环境中威胁的内在能力，但对潜在的分子机制知之甚少。要完全理解这一过程，需要了解潜在的神经回路沿着，并有能力测量，最重要的是，扰乱它们的活动。这在复杂的脊椎动物回路中很难实现。然而，无脊椎动物回路具有明确的神经解剖学和定量行为，是破译指导复杂输出的潜在机制的理想选择。该提案旨在了解无脊椎动物大脑模型中编码威胁反应（行为和生理）的神经机制。线虫，秀丽隐杆线虫，提供了一个独特的机会，分析，使用多尺度的方法，基因，细胞和电路，调节复杂的行为。Chalasani实验室开发了一种新的威胁行为模型，使用C。线虫和第二种线虫，太平洋棱纹线虫 一个饥饿的Pristionchus会攻击并吞噬C。30分钟内就能吃到美味的C.反过来，秀丽线虫也会避开Pristionchus及其分泌物。 除了这种行为反应之外，C.秀丽线虫也在暴露于Pristionchus时激活线粒体应激。拟议的研究计划的目标是确定在这个模型系统中的细胞和分子机制调节回避行为。已经确定，包括三个新的感觉神经元（ASJ，ASK和ASI）的新神经回路驱动回避行为和生理应激反应。具体目标1将确定这种神经回路和相关的神经递质和受体，调节捕食者回避和线粒体应激反应。 目标2将优化一个自动化行为平台，以快速分析大量蠕虫的行为，并对影响回避行为的基因进行大规模筛选。一项初步筛选已经确定了4个调节回避行为所需的有趣基因。 这些包括TRPV通道（可能是Pristionchus传感机制的一部分），谷氨酸转运蛋白和5-羟色胺生物合成酶和5-羟色胺再摄取转运蛋白。目标3的重点是验证这些和其他来自遗传筛选的候选人。这些研究将阐明神经回路如何在突触、神经回路和整个生物体的水平上处理有关环境威胁的信息。此外，我们将确定神经回路如何整合谷氨酸和5-羟色胺信号以产生复杂行为的基本原则和保守机制。