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

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.

项目概要携带疾病的蚊子的交配、寻找宿主和血粉获取行为是由一种一系列化学感应和进食附属物对于传播周期至关重要。按蚊 (Anopheles) 与许多其他环境刺激物合作或区分宿主气味线索（利好素） coluzzii 蚊子使用敏锐的嗅觉/味觉，依赖于至少三个大的化学感应家族受体：这些受体是味觉 (AcGrs)、气味 (AcOrs) 和变异离子型 (AcIrs) 受体在外周化学感应组织中表达，并将有关化学环境的信息传递给与高度分化且研究相对充分的 AcOr 家族相比，AcIr 化学感受器家族。很大程度上是保守的并且相对知之甚少。我们小组利用最先进的转基因生产和基因靶向方法进行的初步研究已经开始探索 AcIr76b（专性 IR 共受体三联体之一）的表达和功能。研究证实了广泛的表达谱，更重要的是，已经开始阐明红外信号传导在调节对许多气味线索的反应中发挥作用，这些气味线索是重要的蚊子行为的基础，例如这使我们重新认识到 AcIrs 在神经元中发挥着关键作用。对尚未确定的交配和吸血线索以及几种公认的人类皮肤的敏感性存在于成体触角、上颌须、唇瓣和跗节上的感觉器中的气味剂，例如，凹槽。 peg 感受器对重要的人类来源的利他素（如氨、乳酸和丁胺——但其中的神经元表达 AcIr76b 和其他 AcIrs，但不表达 AcOrs。提案中，我们寻求全面阐明 AcIrs 的分子功能及其潜在作用宿主利好素、交配和供血受体，从而阐明化学感应的关键成分疟疾媒介蚊子 An. coluzzii 的过程拓宽了我们对寻找宿主、血液的认识。 An. coluzzii 以及 Irs 所在的其他传播疾病的蚊子的进食和交配生物学。保存得非常好的可能通过提供新的方法来对人类健康产生重要的未来影响干扰疾病传播。