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.

项目概要/摘要 蚊病媒介控制主要依靠有毒杀虫剂。更环保 另一种方法是利用基于光的行为操纵来吸引害虫到陷阱并驱赶害虫 来自人类居住地。本技术基于蚊子紫外线检测的假设 仅通过眼睛中基于视蛋白的光接收发生。霍姆斯实验室最近发现了更多 中枢大脑神经元中表达的紫外线和短波长感光元件强烈调节 昆虫对光的复杂行为反应。因此，需要纳入这些附加元素 用于病媒控制设计以提高效率。即 CRYPTOCHROME (CRY)，它是经典的 与其在生物钟重置中的作用相关，用蓝光和紫外线激活并增加电 昼夜节律/唤醒神经元的兴奋性。根据我的初步数据，我假设 CRY 与 其他光感受器介导光诱导的神经元电兴奋性，这是复杂的基础 睡眠/觉醒和昼夜节律调节的回避/吸引行为。 我的目标是确定 CRY 光转导的机制，以及我们如何操纵它 机制以及其他光输入来调节对光的复杂行为反应，如果我们可以的话 将这些知识转化为蚊子系统，以进行基于光的控制。我将从检查分子开始 光转导机制是 CRY 介导的昼夜节律/唤醒神经元电兴奋性的基础 目标 1. 接下来，我将测量不同感光器输入的相对贡献，这些输入介导 目标 2 中昼夜节律/唤醒神经元的电生理光反应。最后，我将检查分子 表达日咬与夜咬的转基因果蝇的光转导机制和光响应 目标 3 中的蚊子 CRY。我的研究将有助于开发针对特定物种的创新 LED 设备 在持续对抗媒介传播疾病的过程中控制有害昆虫。 我的资助者托德·霍姆斯博士和我制定了一项培训计划，重点关注我的发展 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 电生理学、行为分析和显微镜学。我计划注册相关课程，参加 研讨会和培训活动，并与该领域的专家建立联系。我的写作和发展 沟通技巧将通过申请赠款/奖学金、手稿开发和 在会议和研讨会上发表演讲。此外，我将通过培训来发展我的指导技能 本科生帮助进行实验和分析数据。我是高度合作研究的一部分 环境，拥有许多电生理学、神经生物学和行为学、显微镜学、遗传学和 我部门的生物信息学。我计划充分利用可用的资源和设施，以便 完成这个提案的目标，也实现我成为一名独立研究科学家的目标。