Identifying Novel Photic Inputs to the Drosophila Circadian/Arousal Neural Network for Behavioral Manipulation

识别果蝇昼夜节律/唤醒神经网络的新光输入以进行行为操纵

• 批准号: 10314992
• 负责人: David Au
• 金额: $ 4.16万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-22 至 2023-07-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10314992
• 关键词: Action Potentials; Acute; Address; Amino Acids; Animals; Arousal; Behavior; Behavior Control; Behavioral Assay; Binding; Bioinformatics; Biological Assay; Brain; C-terminal; Cells; Clock protein; Communicable Diseases; Communication; Complex; Containment; Culicidae; Data; Detection; Development; Devices; Disease Vectors; Drosophila genus; Educational workshop; Electrophysiology (science); Elements; Environment; Environmental Impact; Event; Evoked Potentials; Eye; Fellowship; Flavin-Adenine Dinucleotide; Genetic; Goals; Grant; Habits; Human; Insect Control; Insecta; Insecticides; Knowledge; Lateral; Lead; Light; Manuscripts; Measures; Mediating; Membrane; Mentorship; Methods; Microscopy; Molecular; Mosquito Control; Neurobiology; Neurons; Opsin; Oxidation-Reduction; Pathway interactions; Pesticides; Photoreceptors; Phototransduction; Play; Point Mutation; Research; Resolution; Resources; Rhodopsin; Role; Running; Scientist; Shock; Sleep; Source; System; Tail; Technical Expertise; Technology; Time; Training; Transgenic Organisms; Translating; Ultraviolet Rays; Vector-transmitted infectious disease; Writing; base; behavioral response; biophysical analysis; circadian; circadian pacemaker; cofactor; comparative; cryptochrome; design; disorder prevention; experimental study; fight against; fighting; fly; improved; innovation; loss of function; molecular clock; mutant; neural network; novel; patch clamp; photoactivation; response; skills; skills training; symposium; technical writing; undergraduate student; vector control; vector mosquito; voltage

PROJECT SUMMARY/ABSTRACT Mosquito disease vector control relies mostly on toxic insecticides. A more environmentally friendly alternative is to make use of light-based behavioral manipulation to attract pests to traps and repel pests away from human habitation. The present technology is based on the assumption that mosquito UV light detection occurs solely through opsin-based photoreception in the eyes. The Holmes Lab has recently found additional UV and short wavelength photoreceptive elements expressed in central brain neurons that strongly modulate complex insect behavioral responses to light. Therefore, there is a need to incorporate these additional elements in disease vector control designs for improved efficiency. Namely, CRYPTOCHROME (CRY), which is classically associated with its role in circadian clock resetting, activates with blue- and UV- light and increases the electrical excitability of circadian/arousal neurons. Based on my preliminary data, I hypothesize that CRY coordinates with other photoreceptors to mediate light-induced electrical excitability of neurons, which underlie complex sleep/wake and circadian modulated avoidance/attraction behaviors. My objectives are to determine the mechanism of CRY phototransduction, how we can manipulate that mechanism along with other light inputs to modulate complex behavioral responses to light, and if we can translate that knowledge to a mosquito system for light-based control. I will begin by examining the molecular phototransduction mechanism that underlie CRY-mediated electrical excitability of circadian/arousal neurons in Aim 1. Next, I will measure the relative contribution of different photoreceptor inputs that mediate the electrophysiological photoresponse in circadian/arousal neurons in Aim 2. Last, I will examine the molecular phototransduction mechanism and photic response of transgenic Drosophila expressing day-versus night-biting mosquito CRYs in Aim 3. My research will be useful for developing innovative LED devices for species-specific harmful insect control in the ongoing fight against vector-borne diseases. My Sponsor, Dr. Todd Holmes, and I have developed a training plan to focus on the development of my technical, writing and communication, and mentorship skills. Development of my technical skills will focus heavily on electrophysiology, behavioral assays, and microscopy. I plan to register for relevant courses, attend workshops and training events, and network with experts in the field. Development of my writing and communication skills will be accomplished by applying for grants/fellowship, manuscript development, and presenting at conferences and symposiums. Additionally, I will develop my mentorship skills by training undergraduate students to help run experiments and analyze data. I am a part of a highly collaborative research environment, with many experts in electrophysiology, neurobiology and behavior, microscopy, genetics, and bioinformatics within my department. I plan to fully utilize the resources and facilities available to me in order to accomplish the goals of this proposal, as well as achieve my goal of becoming an independent research scientist.

项目摘要/摘要 蚊子疾病媒介控制主要依赖于毒性杀虫剂。更环保的 替代方案是利用基于轻的行为操纵来吸引害虫陷阱并驱除害虫 来自人类的居住。目前的技术基于蚊子紫外线检测的假设 仅通过眼睛中的基于OPSIN的光感受发生。福尔摩斯实验室最近发现了其他 在中央脑神经元中表达的紫外线和短波长感受性元件，这些元件强烈调节 复杂的昆虫行为对光的反应。因此，有必要合并这些其他元素 在疾病媒介控制设计中，以提高效率。即隐性物（Cry），这是经典的 与其在昼夜节律时钟重置，用蓝色和紫外线激活并增加电气的作用相关 昼夜节律/唤醒神经元的兴奋性。根据我的初步数据，我假设哭泣与 其他光感受器介导神经元的光诱导的电兴奋性，这是复合物的基础 睡眠/唤醒和昼夜节律调节回避/吸引行为。 我的目标是确定哭泣的光转导的机制，我们如何操纵 机制以及其他轻输入，以调节对光的复杂行为反应，如果可以的话 将这些知识转化为蚊子系统，以进行光基控制。我将首先检查分子 循环介导的昼夜节律/唤醒神经元的电兴奋性基础的光转导机制 AIM1。接下来，我将测量介导的不同光感受器输入的相对贡献 AIM 2中的昼夜节律/唤醒神经元中的电生理光响应。最后，我将检查分子 转导机制和转基因果蝇的光反应表达日间夜间吸入 AIM 3中的蚊子Crys。我的研究将有助于开发特定物种特定物种的创新LED设备 在与媒介传播疾病的持续斗争中，有害的昆虫控制。 我的赞助商托德·福尔摩斯（Todd Holmes）博士，我已经制定了一项培训计划，专注于我的发展 技术，写作和沟通以及指导技能。我的技术技能的发展将重点关注 关于电生理学，行为测定和显微镜。我计划注册相关课程，参加 讲习班和培训活动，并与该领域的专家建立联系。我的写作的发展和 沟通技巧将通过申请赠款/奖学金，手稿制定以及 在会议和专题讨论会上呈现。此外，我将通过培训来发展我的指导能力 本科生可以帮助进行实验并分析数据。我是一项高度协作研究的一部分 环境，许多专家在电生理学，神经生物学和行为，显微镜，遗传学和 我部门内的生物信息学。我计划充分利用我可用的资源和设施 实现这一建议的目标，并实现成为一名独立研究科学家的目标。