Identification of mosquito brain neurons that drive blood-feeding behavior

识别驱动吸血行为的蚊子大脑神经元

• 批准号: 10726059
• 负责人: Trevor Sorrells
• 金额: $ 50.25万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-11 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10726059
• 关键词: ATAC-seq; Area; Atlases; Automobile Driving; Behavior; Behavior Control; Biological Assay; Bite; Blood; Brain; Carbon Dioxide; Cells; Cessation of life; Communicable Diseases; Creativeness; Cues; Culicidae; Data; Data Set; Dengue; Disease; Enhancers; Face; Feeding behaviors; Foundations; Gene Expression; Genetic; Genetic Enhancer Element; Genomics; Goals; Hand; Human; Human Bites; Individual; Intervention; Knowledge; Malaria; Maps; Methods; Mosquito-borne infectious disease; Neurobiology; Neurons; Neurosciences; Parasites; Peripheral; Postdoctoral Fellow; Prevention; Role; Sensory; Signal Transduction; Stimulus; Techniques; Testing; Time; Transgenic Organisms; Vertebrates; Virus; Work; Yellow Fever; Zika Virus; behavioral study; cell type; design; feeding; genetic effector; genetic manipulation; improved; innovation; insight; interest; mosquito-borne; multiple omics; neural; neural circuit; neurogenetics; neuronal circuitry; novel strategies; optogenetics; pathogen; prevent; response; sensory integration; sensory stimulus; sensory system; single-cell RNA sequencing; success; tool; transcriptome; transmission process; vector control

PROJECT SUMMARY Mosquitoes transmit numerous pathogens to humans by virtue of their ability to locate and bite vertebrates. Current strategies to prevent these diseases face various limitations and new approaches are needed. One possibility would be to inhibit the neurons in the mosquito brain that direct the behavior of attraction to humans and feeding on blood, but such neurons have not been identified because the tools and knowledge to do so do not exist. This proposal describes my plan to use genetic and sequencing-based approaches to identify the neurons that are required for blood-feeding behavior. I will take advantage of the fact that mosquitoes require multiple human-derived cues, particularly heat and CO2, to engorge on blood. Using gene expression changes in single cells, I will identify neurons that show altered responses specifically in the presence of both stimuli. To enable the genetic targeting of specific cell types of interest, we will create an atlas of enhancer elements that are specific to each cell type in the mosquito brain, using paired single cell RNA and ATAC-seq data. Finally, we will target key neurons for blood feeding using an enhancer driver constructs and combine them with genetic effectors to test whether the neurons are necessary and sufficient for blood feeding behavior. This proposal combines my expertise in computational genomics, transgenic mosquitoes, and behavior to achieve the goal of identifying neurons at a key node in the neural circuits for blood feeding. The identification of these neurons that drive blood feeding would be useful for understanding how they are activated and thus allow the design of more attractive mosquito traps. These neurons, if inactivated, would prevent mosquitoes from biting humans so they also could serve as a potential target to disrupt the spread of mosquito borne illness.

项目概要 蚊子凭借其定位和叮咬脊椎动物的能力，将大量病原体传播给人类。 目前预防这些疾病的策略面临各种局限性，需要新的方法。一 可能性是抑制蚊子大脑中指导吸引人类行为的神经元 并以血液为食，但这种神经元尚未被识别，因为这样做的工具和知识还不够 不存在。该提案描述了我的计划，即使用基于遗传和测序的方法来识别 吸血行为所需的神经元。我会利用蚊子需要的事实 多种人类来源的信号，特别是热量和二氧化碳，会导致血液充沛。利用基因表达变化 在单细胞中，我将识别在两种刺激存在时表现出特定反应改变的神经元。到 能够对感兴趣的特定细胞类型进行遗传靶向，我们将创建一个增强子元件图谱， 使用配对的单细胞 RNA 和 ATAC-seq 数据，针对蚊子大脑中的每种细胞类型。最后， 我们将使用增强子驱动器结构来瞄准关键神经元进行血液喂养，并将它们与 遗传效应器来测试神经元对于吸血行为是否是必要和充分的。这 提案结合了我在计算基因组学、转基因蚊子和行为方面的专业知识，以实现 目标是识别神经回路中关键节点的神经元以进行血液喂养。这些的鉴定 驱动血液供给的神经元将有助于了解它们是如何被激活的，从而允许 设计更具吸引力的捕蚊器。这些神经元如果失活，将阻止蚊子叮咬 人类，因此它们也可以作为阻止蚊媒疾病传播的潜在目标。