Functions of Fam65b protein complex at the basal stereocilia in hearing and deafness
Functions of Fam65b protein complex at the basal stereocilia in hearing and deafness
批准号:
10433855
负责人:
Bo Zhao
金额:
$39.38万
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-07-01 至 2024-02-29
关键词:
ActinsAffectApicalAuditory PerceptionBiochemical PathwayCRISPR/Cas technologyCell physiologyCell surfaceChildCochleaComplexCytoskeletonDataDefectDiseaseEpithelialEventGenerationsGenesGeneticGenomicsGoalsHair CellsHealthHearingHumanIndividualLibrariesLinkLocationMaintenanceMapsMechanicsMicrofilamentsMolecularMorbidity - disease rateMorphogenesisMorphologyMusMutant Strains MiceMutationNamesNervous system structureOutcomePathologyPathway interactionsProcessPropertyProteinsQuality of lifeRegulationResearchRoleSensorineural Hearing LossSensoryShapesSignal TransductionSiteStimulusSurfaceSystemTestingYeastsbasecrosslinkcysteine rich proteindeafnessglutaredoxinhearing impairmentinsightlink proteinmechanotransductionmouse modelmutantnovelprotein complexprotein functionsensorsoundtherapeutic developmentyeast two hybrid system
中文摘要
项目总结/摘要
听力损失是儿童发病的主要原因,在美国,每1,000人中约有2至3人患有听力损失。
美国.虽然对受影响基因的研究已经揭示了对机制的重要见解,但我们只是在
开始了解形态发生事件背后的疾病机制。的总目标
本研究旨在阐明静纤毛的形成和维持的调控机制,
耳蜗毛细胞束,以及导致耳聋的这一过程中的缺陷。我们建议调查
Fam 65 b蛋白复合物在耳蜗毛细胞中的功能及听觉感受。在我们的初步调查中
通过研究,我们已经鉴定了Fam 65 b蛋白复合物中的几种组分。我们已经生成了基因组
使用CRISPR/Cas9系统修饰的小鼠模型。我们采用了免疫染色,并说明了
立纤毛缺陷。基于我们的初步数据,我们假设Fam 65 b蛋白
复合体对耳蜗毛细胞静纤毛束的结构组织至关重要。来测试我们
假设,我们将:i)功能性表征位于基底的Fam 65 b蛋白复合物中的蛋白质
ii)表征Fam 65 b蛋白复合物调节毛发的生化途径
细胞功能,并确定它们调节静纤毛中肌动蛋白细胞骨架的程度; iii)继续
Fam 65 b蛋白复合物中毛细胞蛋白的鉴定。我们的初步数据表明,
我们的方法。我们预计,我们的研究将为分子机制提供新的见解,
形成静纤毛并决定其性质。很有可能,我们的发现可能会将几个与肥胖有关的
基因进入一个共同的分子途径,并提供新的线索,为发展的治疗
治疗某些疾病的方法。
英文摘要
PROJECT SUMMARY/ABSTRACT
Hearing loss is a leading cause of morbidity in children affecting about 2 to 3 out of every 1,000 individuals in
the USA. While the study of affected genes has shed important insights into the mechanisms, we are just at
the beginning to understand the disease mechanisms underlying morphogenetic events. The overall goal of
this research is to elucidate the mechanisms that regulate the formation and maintenance of the stereociliary
bundle of cochlear hair cells, and the defects in this process that cause deafness. We propose to investigate
the functions of Fam65b protein complex in the cochlear hair cells and auditory perceptions. In our preliminary
studies, we have identified several components in the Fam65b protein complex. We have generated genomic
modified mouse models using CRISPR/Cas9 system. We have employed immunostaining and illustrated the
stereociliary defects in these mice. Based on our preliminary data, we hypothesize that Fam65b protein
complex is critical for the structural organization of stereociliary bundle of cochlear hair cells. To test our
hypothesis, we will: i) Functionally characterize proteins in the Fam65b protein complex localized at the basal
region of stereocilia; ii) Characterize the biochemical pathways by which Fam65b protein complex regulate hair
cell function and determine the extent to which they modulate the actin cytoskeleton in stereocilia; iii) Continue
our identification of hair cell proteins in the Fam65b protein complex. Our preliminary data show the feasibility
of our approach. We anticipate that our studies will shed new insights into the molecular machinery that
shapes stereocilia and determines its properties. Quite possibly, our findings may link several deafness-related
genes into a common molecular pathway and provide new leads for the development of therapeutic
approaches for the treatment of some forms of the disease.
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会议论文
Molecular Mechanisms of Aminoglycoside Ototoxicity
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批准号:10569609
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项目类别:
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资助金额:$55.41万
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财政年份:2022
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负责人:Bo Zhao
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依托单位:
Molecular Mechanisms of Aminoglycoside Ototoxicity
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批准号:10443277
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批准号:10266853
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资助金额:$24.9万
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财政年份:2020
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负责人:Bo Zhao
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依托单位:
Optimized MR Fingerprinting for Rapid Volumetric Quantitative Neuroimaging
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批准号:10450170
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项目类别:
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资助金额:$24.9万
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财政年份:2020
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负责人:Bo Zhao
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依托单位:
Optimized MR Fingerprinting for Rapid Volumetric Quantitative Neuroimaging
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批准号:10260805
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项目类别:
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资助金额:$24.9万
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财政年份:2020
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负责人:Bo Zhao
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依托单位:
Functions of Fam65b protein complex at the basal stereocilia in hearing and deafness
-
批准号:10194456
-
项目类别:
-
资助金额:$39.38万
-
财政年份:2018
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负责人:Bo Zhao
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依托单位:
Targeting Epstein-Barr Virus Super-Enhancer
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批准号:9970995
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项目类别:
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资助金额:$44.75万
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财政年份:2016
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负责人:Bo Zhao
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依托单位:
Fam65b function in hearing and deafness
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批准号:9088059
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项目类别:
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资助金额:$25.24万
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财政年份:2016
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负责人:Bo Zhao
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依托单位:
Targeting Epstein-Barr Virus Super-Enhancer
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批准号:10379876
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项目类别:
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资助金额:$44.75万
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财政年份:2016
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负责人:Bo Zhao
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依托单位:
Targeting Epstein-Barr Virus Super-Enhancer
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批准号:10596159
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项目类别:
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资助金额:$44.75万
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财政年份:2016
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负责人:Bo Zhao
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依托单位:
Epstein-Barr Virus Nuclear Protein B Cell Growth Transformation
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批准号:10219163
-
项目类别:
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资助金额:$53.25万
-
财政年份:1987
-
负责人:Bo Zhao
-
依托单位:
Epstein-Barr Virus Nuclear Protein B Cell Growth Transformation
-
批准号:9977926
-
项目类别:
-
资助金额:$53.25万
-
财政年份:1987
-
负责人:Bo Zhao
-
依托单位:
海外基金