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.

项目总结/摘要 控制苔藓病媒介主要依靠有毒杀虫剂。更环保的 另一种方法是利用基于光的行为操纵来吸引害虫进入陷阱并将害虫赶走 从人类居住地。本技术基于蚊子UV光检测 仅通过眼睛中基于视蛋白的光感受发生。霍姆斯实验室最近发现了 UV和短波长光感受元件在中枢脑神经元中表达，其强烈调节 昆虫对光的复杂行为反应因此，有必要纳入这些额外的要素， 用于病媒控制设计以提高效率。也就是说，光致变色（哭），这是经典的 与其在生物钟重置中的作用相关，通过蓝光和紫外线激活， 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 睡眠/觉醒和昼夜调节的回避/吸引行为。 我的目标是确定CRY光转导的机制，我们如何操纵它， 沿着其他光输入来调节对光的复杂行为反应，如果我们能 将这些知识转化为蚊子系统，以进行基于光的控制。我将开始检查 光转导机制，其基础是昼夜节律/唤醒神经元的光介导的电兴奋性， 目标1.接下来，我将测量不同感光细胞输入的相对贡献，这些输入介导了细胞的分裂。 Aim 2中的昼夜节律/唤醒神经元的电生理光响应。最后，我将检查分子 转昼咬与夜咬基因果蝇的光传导机制和光反应 目标3中的蚊子。我的研究将有助于开发创新的LED器件， 在目前防治病媒传播疾病的斗争中，有害昆虫的控制。 我的担保人托德霍姆斯博士和我制定了一个培训计划，重点是发展我的 技术、写作和沟通以及指导技能。我的技术技能的发展将主要集中在 电生理学行为分析和显微镜我打算报名参加相关课程， 讲习班和培训活动，并与该领域的专家建立网络。我写作的发展和 沟通技巧将通过申请赠款/奖学金，手稿开发， 在会议和研讨会上发言。此外，我将通过培训发展我的指导技能， 帮助本科生进行实验和分析数据。我参与了一项高度合作的研究 环境，与许多专家在电生理学，神经生物学和行为，显微镜，遗传学， 生物信息学。我计划充分利用现有的资源和设施， 完成这个提案的目标，以及实现我成为一名独立研究科学家的目标。