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，但是理解的基本分子机制知之甚少。对这一过程的完整理解需要了解潜在的神经回路，并具有测量和最重要的是扰动其活动的能力。这很难在复杂的脊椎动物电路中获得。然而，理想情况下，具有明确定义的神经解剖结构和定量行为的无脊椎动物电路是破译基础机械指导复合输出的理想选择。该建议旨在了解无脊椎动物大脑模型中代码威胁响应（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，可以使用调节复杂行为的多尺度方法，基因，细胞和电路进行分析。 Chalasani Lab使用秀丽隐杆线虫与第二个线虫Pristionchus Pacificus之间的相互作用开发了一种新颖的威胁行为模型。 饥饿的Pristionchus将在30分钟内进攻并吞噬秀丽隐杆线虫。秀丽隐杆线虫反过来将避免Pristionchus及其分泌物。 除了这种行为反应外，秀丽隐杆线虫还在暴露于pristionchus时激活线粒体应力。拟议的研究计划的目标是定义该模型系统中调节回避行为的细胞和分子机制。已经确定，包括三个新的感觉神经元（ASJ，ask和ASI）的新型神经回路驱动避免行为和生理压力反应。具体目标1将鉴定该神经元回路以及调节捕食者回避和线粒体应激反应的相关神经递质和受体。 AIM 2将优化一个自动行为平台，以快速分析大量蠕虫的行为，并为影响回避行为的基因执行大屏幕。试点屏幕已确定了调节回避行为所需的4个有趣的基因。 这些包括TRPV通道（可能是Pristionchus传感机械的一部分），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。 AIM 3专注于从遗传筛选中验证这些和其他候选者。这些研究将阐明神经回路如何处理有关突触，神经回路和整个生物的环境威胁的信息。此外，我们将确定神经回路如何整合谷氨酸和5-羟色胺信号传导以产生复杂行为的基本原理和保守机制。