Fam65b function in hearing and deafness

Fam65b 对听力和耳聋的作用

• 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
• 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

 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。我们在此建议研究与导致耳聋的 Fam65b 突变相关的正常功能和病理生理变化。根据我们的初步数据，我们假设 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) 继续对 Fam65b(-/-) 毛细胞进行表征； ii)表征Fam65b功能域； iii) 寻找在发束形态发生中功能性合作的 Fam65b 相互作用伙伴。我们的初步数据显示了我们方法的可行性。我们预计我们的研究将为塑造静纤毛并决定其特性的分子机制提供新的见解。很可能，我们的发现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，并为开发治疗某些疾病的治疗方法提供新的线索。