Fam65b function in hearing and deafness

Fam65b 对听力和耳聋的作用

基本信息

批准号：
9088059
负责人：
Bo Zhao
金额：
$ 25.24万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-05 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9088059
关键词：
Actins Address Affect Apical Binding Bundling Cell surface Cochlea Cytoskeletal Modeling Data Defect Disease Event Generations Genes Genetic Goals Hair Hair Cells Health Hearing Hearing Impaired Persons Height Human Individual Integral Membrane Protein Knock-out Length Libraries Link Maintenance Maps Mechanical Stimulation Mechanics Membrane Microfilaments Molecular Molecular Machines Morphogenesis Mus Mutation Nervous system structure PTPRR gene Pathway interactions Population Process Property Proteins Quality of life Resolution Scanning Electron Microscopy Sensorineural Hearing Loss Shapes Signal Transduction Site Staging Stereocilium Stimulus Structure Surface Technology Tertiary Protein Structure Testing Transmission Electron Microscopy Yeasts base crosslink deafness design dimer hearing impairment insight knock-down microscopic imaging public health relevance sensor sound therapeutic development tool yeast two hybrid system

项目摘要

DESCRIPTION (provided by applicant): The overall goal 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 here to investigate the normal functions and the pathophysiological changes associated with Fam65b mutation that cause deafness. Based on our preliminary data, we hypothesize that Fam65b is critical for the structural organization of stereociliary bundle of cochlear hair cells. To test our hypothesis, we will: i) continue our characterization of Fam65b(-/-) hair cells; ii) characterize Fam65b functiona domains; iii) look for interaction partners for Fam65b that functionally cooperate in hair bundle morphogenesis. 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.

描述（由申请人提供）：总体目标是阐明调节耳蜗毛细胞静纤毛束的形成和维持的机制，以及该过程中导致耳聋的缺陷。与导致耳聋的 Fam65b 突变相关的病理生理变化根据我们的初步数据，我们认为 Fam65b 对于耳蜗毛细胞静纤毛束的结构组织至关重要。为了检验我们的假设，我们将：i) 继续表征 Fam65b(-/-) 毛细胞；ii) 表征 Fam65b 功能域；iii) 寻找在发束形态发生中功能合作的 Fam65b 相互作用伙伴。我们预计我们的研究将为形成静纤毛并确定其特性的分子机制提供新的见解，我们的发现很可能将几个与耳聋相关的基因连接到一个共同的分子途径中。并为某些疾病的治疗方法的开发提供新的线索。