Hormone regulation of olfactory neuron function in the Zika vector Aedes aegypti
寨卡病毒载体埃及伊蚊中嗅觉神经元功能的激素调节
基本信息
- 批准号:10247565
- 负责人:
- 金额:$ 5.1万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-09-01 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAedesAffectAnatomyAnopheles GenusAntibodiesArbovirusesBehaviorBehavioralBindingBioinformaticsBloodBrainCalciumCarbon DioxideCellsChIP-seqChikungunya feverCuesCulicidaeDataDengueDengue FeverDetectionDevelopmentDiseaseDisease VectorsDissectionEcdysoneEcdysteroneEnvironmentFeeding behaviorsFemaleGene ExpressionGenesGenetic TranscriptionGenomeGenomicsGoalsHealthHemolymphHormonesHumanHuman BitesImageIngestionInjectionsInsectaLabelLaboratoriesLigandsLobeMaxillaMediatingNeuronsNuclear Hormone ReceptorsOdorant ReceptorsOdorsOrganOrganismOutcomeOvaryPathway interactionsPerceptionPhysiologicalPlayPresynaptic TerminalsProcessProtein IsoformsProteinsPublic HealthPublishingReceptor GeneReceptor SignalingRegulationResearchResearch TrainingRoleSignal PathwaySignal TransductionSmell PerceptionSystemTestingTissuesWorkYellow FeverZIKAchikungunyachromatin immunoprecipitationdisease transmissionecdysone receptoreggexperiencefeedinggenetic manipulationhormonal signalshormone regulationinsightnovelolfactory receptorolfactory sensory neuronsoptogeneticspreventprogramsreceptorresponsesensorskillssteroid hormonetooltranscription factortranscriptometwo-photonvectorvector controlzika fever
项目摘要
PROJECT SUMMARY/ABSTRACT
Aedes aegypti mosquitoes spread arboviruses including Zika, chikungunya, dengue, and yellow fever
by biting and feeding on the blood of multiple human hosts. Understanding the mechanisms by which
mosquitoes are attracted to humans and disrupting this deadly behavior will have profound implications for
public health. Female Ae. aegypti utilize human cues such as carbon dioxide, heat, and odor to efficiently
locate a host. These mosquitoes naturally experience periods when this strong attraction to humans is
suppressed, including following a blood-meal. The mechanisms underlying host-seeking suppression are
unknown. The objective of this proposal is to establish how endogenous signaling pathways regulate
chemosensory circuits necessary for mosquito host-seeking behavior.
The physiological state of the female mosquito changes significantly after ingestion of a blood-meal,
when she must digest the protein in the blood to develop eggs. The steroid hormone 20-hydroxecdysone (20E)
is critical for the egg-development process, and levels of 20E are upregulated in the hemolymph (insect blood)
shortly after the blood-meal. In preliminary studies, we demonstrated that feeding 20E to non-blood-fed female
mosquitoes robustly inhibited host-seeking drive. To determine if 20E is acting directly in the brain, Ae. aegypti
brains were immunostained with an antibody for an isoform of the 20E receptor, ecdysone receptor isoform A
(EcR-A). These studies showed that EcR-A is found in specific antennal lobe glomeruli. The antennal lobe
receives projections from chemosensory neurons in the antennae, maxillary palps, and proboscis,
chemosensory organs that are critical for the detection of human odor and carbon dioxide. Understanding how
20E and EcR-A function in the antennal lobe and chemosensory tissues offers mechanistic insights into the
pathways involved in host-seeking behavior. In Aim 1 of this proposal we will characterize EcR-A circuitry in Ae.
aegypti brains and investigate 20E-dependent changes in chemosensory neuron activity. In Aim 2 of the
proposal, we will investigate how 20E and EcR-A regulate expression of olfactory receptors and genes
required for chemosensory signaling machinery in the antenna and palps. It is known that the expression of
olfactory receptors changes after the blood-meal, but the transcriptional mechanism for this regulation is
unknown. EcR-A is a nuclear hormone receptor and transcription factor, and 20E-mediated changes in gene
expression of receptors and signaling machinery in chemosensory neurons is one mechanism that can alter
mosquito responses to host cues after a blood-meal. This research training plan will take place in a highly
supportive laboratory environment and will develop skills in genetic manipulation, live imaging, and
bioinformatics. These studies will contribute fundamental insights into olfactory processing in mosquitoes as
well as provide novel targets for vector control.
项目摘要/摘要
埃及伊蚊传播的虫媒病毒包括寨卡病毒、基孔肯雅热、登革热和黄热病
通过叮咬和吸食多个人类宿主的血液。了解通过哪些机制
蚊子会被人类吸引,扰乱这种致命的行为将对
公共卫生。雌性Ae.埃及伊蚊利用人类的线索,如二氧化碳,热量和气味,有效地
找到一台主机。这些蚊子自然会经历这样一段时期,这种对人类的强烈吸引力
被压制,包括在吃了一顿血餐之后。抑制宿主寻找的潜在机制是
未知。这项建议的目标是确定内源性信号通路如何调节
蚊子寻找寄主行为所必需的化学感官回路。
雌性蚊子摄食血粉后,生理状态发生显著变化,
当她必须消化血液中的蛋白质以发育卵子时。类固醇激素20-羟基蜕皮酮(20E)
对卵子发育过程至关重要,血淋巴(昆虫血)中的20E水平上调。
在吃完血餐后不久。在初步研究中,我们证明了给未吸血的雌性喂食20E
蚊子强烈地抑制了寻找寄主的动力。为了确定20E是否直接作用于大脑,Ae。埃及伊蚊
用20E受体亚型--蜕皮激素受体亚型A的抗体对大脑进行免疫染色
(ECR-A)。这些研究表明,ECR-A存在于特定的触角小球中。触角叶
从触角、上颌触须和鼻子的化学感觉神经元接受投射,
对检测人类气味和二氧化碳至关重要的化学感官。了解如何
20E和ECR-A在触角叶和化学感觉组织中的功能提供了对
参与寄主寻找行为的途径。在本提案的目标1中,我们将描述Ae中的ECR-A电路。
并研究20E依赖的化学感觉神经元活性的变化。在目标2中,
我们将研究20E和ECR-A如何调节嗅觉受体和基因的表达
天线和触摸屏中的化学传感信号机械所需的。众所周知,表达的
嗅觉受体在血餐后会发生变化,但这种调节的转录机制是
未知。ECR-A是一种核激素受体和转录因子,20E介导的基因变化
受体和信号机制在化学感觉神经元中的表达是一种可以改变的机制
蚊子在进食一顿血后对寄主提示的反应。这项研究培训计划将在一个高度
支持实验室环境,并将发展基因操作、实时成像和
生物信息学。这些研究将有助于对蚊子嗅觉处理的基本见解
并为病媒生物控制提供了新的靶点。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Two novel, tightly linked, and rapidly evolving genes underlie Aedes aegypti mosquito reproductive resilience during drought.
在干旱期间,两个小说,紧密联系和迅速发展的基因是埃及埃及蚊子生殖弹性的基础。
- DOI:10.7554/elife.80489
- 发表时间:2023-02-06
- 期刊:
- 影响因子:7.7
- 作者:Venkataraman K;Shai N;Lakhiani P;Zylka S;Zhao J;Herre M;Zeng J;Neal LA;Molina H;Zhao L;Vosshall LB
- 通讯作者:Vosshall LB
RNA In Situ Hybridization and Immunohistochemistry to Visualize Gene Expression in Peripheral Chemosensory Tissues of Mosquitoes.
RNA 原位杂交和免疫组织化学可视化蚊子外周化学感应组织中的基因表达。
- DOI:10.1101/pdb.top107700
- 发表时间:2023
- 期刊:
- 影响因子:0
- 作者:Herre,Margaret;Greppi,Chloe
- 通讯作者:Greppi,Chloe
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