Membrane properties of the OHC system
OHC 系统的膜特性
基本信息
- 批准号:9364111
- 负责人:
- 金额:$ 64.77万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-06-12 至 2022-05-31
- 项目状态:已结题
- 来源:
- 关键词:AchievementAcousticsAnionsAreaAuditoryAutomobile DrivingBasilar MembraneBehaviorBindingBiophysicsCRISPR/Cas technologyCalibrationCaviaCell membraneCell physiologyCellsCharacteristicsChargeChloride IonChloridesCochleaConsultCouplingCryoelectron MicroscopyDataDevelopmentDistantDropsElectric CapacitanceElectrophysiology (science)ElementsEnsureEnvironmentEquilibriumEventFamily memberFrequenciesFunctional disorderGoalsHair CellsHearingHomologous GeneHumanIn VitroInvestigationIon ChannelIonsKineticsKnock-in MouseLateralLeadMammalsMeasurementMeasuresMechanicsMembraneMembrane PotentialsModelingModificationMolecularMolecular BiologyMolecular ConformationMolecular MotorsMonitorMotorMotor NeuronsMovementMusNational Institute on Deafness and Other Communication DisordersOrganOuter Hair CellsPathologyPhasePhysiologicalPlant RootsPredispositionProcessPropertyProteinsPublishingReportingResearchResolutionRoleSaint Jude Children&aposs Research HospitalSensorySpeechStrategic PlanningStretchingStructureStudy modelsSystemTechniquesTestingTimeViralbasebiophysical analysisbiophysical propertiescell typecohesiondata modelingexperimental studyextracellularinterestnon-invasive monitorrat Pres proteinrelating to nervous systemsensorsingle moleculestable cell linevibrationvoltage
项目摘要
The cochlea is composed of a variety of cell types including sensory, supporting and neural elements.
Taken together, these cells comprise a functionally intricate and cohesive electrical unit that initiates
the analysis of acoustic information within our environment. We capitalize on the in vitro approach,
including isolated cochlea explants, single cell, and more recently stable cell lines to elucidate cochlear
cell function; the strategy is to characterize basic properties prior to integration into a cohesive
understanding of the organ. Currently, the overarching aim of this project is focused on determining the
biophysical properties of key membrane components of the outer hair cell (OHC), one of the major
players in auditory function, using a balance of electrophysiology, molecular biology, modelling and
high resolution cryo-EM. Though we have made significant progress on many fronts since our last
renewal in 2010, we now focus on three specific research topics that evolve from our most significant
accomplishments. In particular, one of the main areas of our investigations has been and will be the
influence of anions on the OHC molecular motor’s (prestin, SLC26a5) electro-mechanical activity. This
ion is at the root of cochlear amplification (Santos-Sacchi et al., 2006). Indeed, the NIDCD’s 2012-2016
Strategic Plan specifically identifies understanding anion control of hearing as a key goal. The three
aims are 1) to evaluate the chloride-dependent kinetic behavior of OHC nonlinear capacitance and
electromotility, 2) to characterize intracellular chloride movements in the prestin-transfected HEK cell
and OHC with a new prestin-fused YFP chloride sensor we created, and 3) to determine the high
resolution structure of prestin (SLC26a5) and its closest mammalian family member SLC26a6 using
cryo-EM, with the goal of identifying conformational changes due to chloride and voltage. We
hypothesize that understanding these molecular activities will aid in understanding how the OHC
enables us to hear so well and in turn how micro-environmental influences may lead to pathologies of
the OHC that afflict millions.
耳蜗由多种细胞类型组成,包括感觉细胞、支持细胞和神经细胞。
总而言之,这些细胞组成了一个功能复杂且具有凝聚力的电气单元,可以启动
对我们环境中的声学信息进行分析。我们利用体外方法,
包括分离的耳蜗外植体、单细胞和最近稳定的细胞系,以阐明耳蜗
细胞功能;该策略是在整合为有凝聚力的产品之前先表征基本属性
对器官的了解。目前,该项目的总体目标是确定
外毛细胞 (OHC) 关键膜成分的生物物理特性,是主要的细胞膜成分之一
听觉功能的参与者,利用电生理学、分子生物学、建模和
高分辨率冷冻电镜。尽管自上次以来我们在许多方面取得了重大进展
2010 年更新后,我们现在专注于三个具体的研究主题,这些主题是从我们最重要的
成就。特别是,我们调查的主要领域之一已经并将是
阴离子对 OHC 分子马达(prestin,SLC26a5)机电活动的影响。这
离子是耳蜗放大的根源(Santos-Sacchi 等,2006)。事实上,NIDCD 2012-2016 年
战略计划明确将了解阴离子控制听力作为关键目标。三个
目标是 1) 评估 OHC 非线性电容的氯化物依赖性动力学行为,以及
电动性,2) 表征 prestin 转染的 HEK 细胞中的细胞内氯离子运动
和 OHC 与我们创建的新型预熔 YFP 氯化物传感器,以及 3) 确定高
使用 prestin (SLC26a5) 及其最接近的哺乳动物家族成员 SLC26a6 的分辨率结构
冷冻电镜,目的是识别氯离子和电压引起的构象变化。我们
假设了解这些分子活动将有助于了解 OHC 如何
使我们能够很好地听到声音,进而了解微环境的影响如何导致疾病
困扰数百万人的 OHC。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOSEPH R SANTOS-SACCHI其他文献
JOSEPH R SANTOS-SACCHI的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOSEPH R SANTOS-SACCHI', 18)}}的其他基金
Membrane properties of cells comprising the OHC system
构成 OHC 系统的细胞的膜特性
- 批准号:
7157225 - 财政年份:2005
- 资助金额:
$ 64.77万 - 项目类别:
相似海外基金
Nonlinear Acoustics for the conditioning monitoring of Aerospace structures (NACMAS)
用于航空航天结构调节监测的非线性声学 (NACMAS)
- 批准号:
10078324 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
BEIS-Funded Programmes
ORCC: Marine predator and prey response to climate change: Synthesis of Acoustics, Physiology, Prey, and Habitat In a Rapidly changing Environment (SAPPHIRE)
ORCC:海洋捕食者和猎物对气候变化的反应:快速变化环境中声学、生理学、猎物和栖息地的综合(蓝宝石)
- 批准号:
2308300 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Continuing Grant
University of Salford (The) and KP Acoustics Group Limited KTP 22_23 R1
索尔福德大学 (The) 和 KP Acoustics Group Limited KTP 22_23 R1
- 批准号:
10033989 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Knowledge Transfer Partnership
User-controllable and Physics-informed Neural Acoustics Fields for Multichannel Audio Rendering and Analysis in Mixed Reality Application
用于混合现实应用中多通道音频渲染和分析的用户可控且基于物理的神经声学场
- 批准号:
23K16913 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Combined radiation acoustics and ultrasound imaging for real-time guidance in radiotherapy
结合辐射声学和超声成像,用于放射治疗的实时指导
- 批准号:
10582051 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Comprehensive assessment of speech physiology and acoustics in Parkinson's disease progression
帕金森病进展中言语生理学和声学的综合评估
- 批准号:
10602958 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
The acoustics of climate change - long-term observations in the arctic oceans
气候变化的声学——北冰洋的长期观测
- 批准号:
2889921 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Studentship
Collaborative Research: Estimating Articulatory Constriction Place and Timing from Speech Acoustics
合作研究:从语音声学估计发音收缩位置和时间
- 批准号:
2343847 - 财政年份:2023
- 资助金额:
$ 64.77万 - 项目类别:
Standard Grant
Flow Physics and Vortex-Induced Acoustics in Bio-Inspired Collective Locomotion
仿生集体运动中的流动物理学和涡激声学
- 批准号:
DGECR-2022-00019 - 财政年份:2022
- 资助金额:
$ 64.77万 - 项目类别:
Discovery Launch Supplement
Collaborative Research: Estimating Articulatory Constriction Place and Timing from Speech Acoustics
合作研究:从语音声学估计发音收缩位置和时间
- 批准号:
2141275 - 财政年份:2022
- 资助金额:
$ 64.77万 - 项目类别:
Standard Grant