Characterization of Ionotropic Receptors in Mating and Blood Feeding in Anopheles mosquitoes

按蚊交配和吸血中离子型受体的表征

基本信息

批准号：
10736638
负责人：
LAURENCE J ZWIEBEL
金额：
$ 49.32万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-06-02 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10736638
关键词：
Address Adult Afferent Neurons Aldehydes Amines Ammonia Anopheles Genus Arboviruses Behavior Behavioral Behavioral Assay Biological Assay Biology Blood Brain CRISPR/Cas technology Carboxylic Acids Chemicals Chemoreceptors Complex Cues Culicidae Data Dengue Disease Electrodes Electrophysiology (science)Environment Etiology Family Family member Female Filariasis Future Gene Targeting Hand Health Human Human Bites Imines In Situ Hybridization Individual Intervention Kairomones Knock-in Lactic acid Larva Malaria Maps Maxilla Mediating Molecular Mosquito-borne infectious disease Neurons Odors Oocytes Partner in relationship Peripheral Phenotype Pheromone Phylogenetic Analysis Physiological Play Population Sizes Public Health Receptor Gene Reporter Genes Research Role Semiochemicals Sensory Sensory Process Sensory Receptors Signal Transduction Skin Smell Perception Stimulus System Taste Perception Tissues Transgenic Organisms Variant Vectorial capacity Volatilization Xenopus laevis ZIKA adult nutrition appendage base design disease transmission feeding improved in vivo loss of function malaria transmission mutant neurogenetics novel olfactory receptor preference programs receptor response sensory mechanism transcriptome transmission process vector vector control vector mosquito voltage clamp

Address Adult Afferent Neurons Aldehydes Amines Ammonia Anopheles Genus Arboviruses Behavior Behavioral Behavioral Assay Biological Assay Biology Blood Brain CRISPR/Cas technology Carboxylic Acids Chemicals Chemoreceptors Complex Cues Culicidae Data Dengue Disease Electrodes Electrophysiology (science)Environment Etiology Family Family member Female Filariasis Future Gene Targeting Hand Health Human Human Bites Imines In Situ Hybridization Individual Intervention Kairomones Knock-in Lactic acid Larva Malaria Maps Maxilla Mediating Molecular Mosquito-borne infectious disease Neurons Odors Oocytes Partner in relationship Peripheral Phenotype Pheromone Phylogenetic Analysis Physiological Play Population Sizes Public Health Receptor Gene Reporter Genes Research Role Semiochemicals Sensory Sensory Process Sensory Receptors Signal Transduction Skin Smell Perception Stimulus System Taste Perception Tissues Transgenic Organisms Variant Vectorial capacity Volatilization Xenopus laevis ZIKA adult nutrition appendage base design disease transmission feeding improved in vivo loss of function malaria transmission mutant neurogenetics novel olfactory receptor preference programs receptor response sensory mechanism transcriptome transmission process vector vector control vector mosquito voltage clamp

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项目摘要

Project Summary Mating, host-seeking and blood-meal-acquisition behaviors in disease-carrying mosquitoes are facilitated by an array of chemosensory and feeding appendages that are critical for transmission cycles. In order to find a mating partner or distinguish host odor cues (kairomones) from numerous other environmental stimuli, Anopheles coluzzii mosquitoes use a keen sense of smell/taste that relies on at least three large families of chemosensory receptors: these are the gustatory (AcGrs), odorant (AcOrs) and variant ionotropic (AcIrs) receptors that are expressed in peripheral chemosensory tissues and convey information about the chemical environment to the brain. In contrast to the highly divergent and relatively well-studied AcOr family, the AcIr family of chemoreceptors is largely conserved and relatively poorly understood. Preliminary studies from our group utilizing state-of-the-art transgenic reporters and gene-targeting approaches have begun to explore the expression and function of AcIr76b, one of the triad of obligate IR co-receptors. These studies confirm broad expression profiles and, more importantly, have begun to elucidate the essential role that IR signaling plays in mediating responses to many odor cues that underlie important mosquito behaviors, such as mating and host seeking/blood feeding. This has led us to hypothesize that AcIrs play a critical role in neuronal sensitivity to as-yet undefined mating and blood-feeding cues as well as several well-established human skin odorants in sensilla that reside on the adult antennae, maxillary palps, labella, and tarsi. For example, grooved- peg sensilla are responsive to important human-derived kairomones—such as ammonia, lactic acid and butylamine—yet the neurons housed within them express AcIr76b and other AcIrs but not AcOrs. In this proposal, we seek to comprehensively elucidate the molecular functionality of AcIrs and their potential roles as host kairomone, mating and blood-feeding receptors and thus clarify key components of the chemosensory processes in the malaria vector mosquito An. coluzzii. Broadening our understanding of the host-seeking, blood- feeding, and mating biology of An. coluzzii and indeed other disease-transmitting mosquitoes in which Irs are extremely well conserved may have important future implications for human health by providing new ways to interfere with disease transmission.

项目摘要通过疾病的蚊子中的交配，寻求宿主和鲜血的进取行为是由化学感应和喂养附属物阵列对于传输周期至关重要。为了找到交配合作伙伴或区分宿主气味提示（Kairomones）与许多其他环境刺激，肛门 Coluzzii蚊子使用敏锐的嗅觉/味道，依赖至少三个大型化学感应家庭受体：这些是味道（ACGRS），气形（ACOR）和变体离子（ACIRS）受体在外围化学感应组织中表达，并将有关化学环境的信息传达给脑。与高度分歧和相对研究的ACOR家族相反，ACIR的化学感受器家族在很大程度上是保守的，并且相对较少理解。我们小组的初步研究利用最先进的转基因记者和靶向基因的方法已经开始探索ACIR76B的表达和功能，ACIR76B是专性的IR共受体三合会之一。这些研究证实了广泛的表达谱，更重要的是，已经开始阐明 IR信号在对许多重要的蚊子行为基础的许多气味线索的中介反应中发挥作用，作为交配和宿主寻求/献血。这使我们假设ACIR在神经元中起着至关重要的作用对尚未定义的交配和喂养提示以及几种已建立的人类皮肤的敏感性居住在成年触角，上颌par，Labela和Tarsi上的感觉的气味剂。例如，凹槽 - PEG Sensora对重要的人类衍生的Kairomons有反应，例如氨，乳酸和丁胺 - 内包含的神经元表达ACIR76B和其他ACIR，但不表达ACORS。在这个提案，我们寻求全面阐明ACIR的分子功能及其潜在作用宿主的kairomone，交配和喂食受体，因此阐明了化学感应的关键组成部分疟疾媒介蚊子的过程。 coluzzii。扩大我们对寻求宿主，鲜血的理解喂养和交配生物学。 Coluzzii以及IRS所在的其他疾病传播的蚊子非常保守的人可能会通过提供新的方式来对人类健康产生重要的影响干扰疾病传播。