Mechanisms of chemosensory recognition
化学感应识别机制
基本信息
- 批准号:10644006
- 负责人:
- 金额:$ 44.51万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-07-01 至 2027-06-30
- 项目状态:未结题
- 来源:
- 关键词:AddressAfferent NeuronsAmino AcidsAnimalsBehavioralCalciumCellsCharacteristicsChemicalsCodeCollectionColor VisionsCuesDataDecision MakingDetectionDevelopmentDisadvantagedEctopic ExpressionEquipment and supply inventoriesExhibitsFamilyFoodG-Protein-Coupled ReceptorsGenesGoalsHarvestHumanImageIn VitroIndividualLaboratoriesLengthLigand BindingLigandsLightLinkMapsMeasuresMicroscopyModelingMolecularMolecular ConformationMutagensOlfactory PathwaysOpticsOutputPartner in relationshipPharmacologic SubstancePhysiologicalPopulationPropertyProteinsReceptor ActivationReceptor GeneRetinal ConeRoleSensorySequence HomologySiteSmell PerceptionSpecificitySteroidsStimulusStructureStructure-Activity RelationshipSulfateSystemTechniquesTestingVertebral columnVolatilizationVomeronasal SystemsWorkblindcandidate identificationcarboxylatecarboxylationcell typechemical bindingcombinatorialcomputerized toolsfeature detectionflexibilityfunctional groupinsightmembernovelolfactory receptorpharmacophorepredicting responsereceptorresponsescreeningsensory systemtoolvomeronasal organ
项目摘要
ABSTRACT
The olfactory system encodes and analyzes odorants. Chemicals bind to members of large families of receptor
proteins tuned to different chemical features. While we have a comprehensive inventory of the receptor genes
that underlie olfactory detection, we are far from having a similarly comprehensive understanding of the
chemical features detected by olfactory systems.
This proposal leverages four developments—the ability to record the output of an entire olfactory
system (the vomeronasal system), a large and structurally-rigid class of odorants (sulfated, carboxylated, and
glucuronidated steroids), a new tool to identify the receptor gene(s) that have particular ligand detection
profiles, and a new tool for ectopically expressing a chosen receptor gene and studying its function—to
develop the first system-wide understanding of how an olfactory system represents the chemical world. The
overarching goal is to develop insights analogous to (and with similar predictive power to) the role of cone
photoreceptor tuning curves in our understanding of color vision.
The specific aims of the proposal are (1) to reveal new principles of combinatorial coding through a
system-wide analysis of the vomeronasal system’s coverage, redundancy, and specificity via a large ligand
screen and quantitative analysis of the structural features required for activating each receptor; and (2) to
reveal relationships between receptor sequence and odorant structure by deorphanizing a large subfamily of
vomeronasal receptor genes. Preliminary data suggest that structural rigidity of steroid metabolites
contributes greatly to the tractability of these aims, supporting quantitative and predictive analysis on a
system-wide scale.
摘要
嗅觉系统编码和分析气味。化学物质与受体大家族的成员结合
具有不同化学特征的蛋白质。虽然我们有一个全面的受体基因清单,
这是嗅觉检测的基础,我们还远没有对嗅觉检测有类似的全面了解。
嗅觉系统检测到的化学特征。
这项提议利用了四项发展-记录整个嗅觉输出的能力
犁鼻系统(vomeronasal system)是一个庞大的、结构刚性的气味物质(硫酸化的、羧基化的和
葡萄糖醛酸化类固醇),一种鉴定具有特定配体检测的受体基因的新工具
和一种用于异位表达所选受体基因并研究其功能的新工具,
开发第一个系统范围内的嗅觉系统如何代表化学世界的理解。的
总体目标是发展类似于(和类似的预测能力)锥的作用的见解
光感受器调谐曲线在我们对色觉的理解中。
该提案的具体目标是:(1)通过一个新的组合编码原理,
通过一个大的配体对犁鼻系统的覆盖、冗余和特异性进行全系统分析
筛选和定量分析激活每种受体所需的结构特征;和(2)
揭示受体序列和气味结构之间的关系,通过去乙酰化一个大的亚家族,
犁鼻受体基因初步数据表明类固醇代谢物的结构刚性
大大有助于这些目标的可追踪性,支持定量和预测分析,
全系统规模。
项目成果
期刊论文数量(1)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
STARDUST: a pipeline for the unbiased analysis of astrocyte regional calcium dynamics.
STARDUST:星形胶质细胞区域钙动态公正分析的管道。
- DOI:10.1101/2024.04.04.588196
- 发表时间:2024
- 期刊:
- 影响因子:0
- 作者:Wu,Yifan;Dai,Yanchao;Lefton,KatherynB;Holy,TimothyE;Papouin,Thomas
- 通讯作者:Papouin,Thomas
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Timothy Holy其他文献
Timothy Holy的其他文献
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{{ truncateString('Timothy Holy', 18)}}的其他基金
The WUSTL PREP post-bacc program to enhance doctoral readiness in neuroscience
WUSTL PREP post bacc 项目旨在提高神经科学博士的准备程度
- 批准号:
10611674 - 财政年份:2023
- 资助金额:
$ 44.51万 - 项目类别:
Neuroscience Training Program at Washington University
华盛顿大学神经科学培训项目
- 批准号:
10441245 - 财政年份:2021
- 资助金额:
$ 44.51万 - 项目类别:
Neuroscience Training Program at Washington University
华盛顿大学神经科学培训项目
- 批准号:
10204331 - 财政年份:2021
- 资助金额:
$ 44.51万 - 项目类别:
Neuroscience Training Program at Washington University
华盛顿大学神经科学培训项目
- 批准号:
10656326 - 财政年份:2021
- 资助金额:
$ 44.51万 - 项目类别:
SULFATED STEROIDS AS NATURAL LIGANDS OF MOUSE PHEROMONE-SENSING NEURONS
硫酸类固醇作为小鼠信息素感知神经元的天然配体
- 批准号:
8361423 - 财政年份:2011
- 资助金额:
$ 44.51万 - 项目类别:
SULFATED STEROIDS AS NATURAL LIGANDS OF MOUSE PHEROMONE-SENSING NEURONS
硫酸类固醇作为小鼠信息素感知神经元的天然配体
- 批准号:
8168833 - 财政年份:2010
- 资助金额:
$ 44.51万 - 项目类别:
WATCHING ACTION POTENTIALS IN INTACT NEURONAL CIRCUITS
观察完整神经回路中的动作电位
- 批准号:
7846059 - 财政年份:2009
- 资助金额:
$ 44.51万 - 项目类别:
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