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（由适用提供）：总体目标是阐明调节耳蜗毛细胞立体丝束的形成和维护的机制，以及在此过程中导致死亡性的缺陷。我们在这里建议研究正常功能和与FAM65B突变相关的病理生理变化。根据我们的初步数据，我们假设FAM65B对于立体毛毛细胞的立体束结构组织至关重要。为了检验我们的假设，我们将：i）继续我们对FAM65b（ - / - ）毛细胞的表征； ii）表征FAM65B功能域； iii）寻找FAM65B的相互作用伙伴，该伙伴在束束形态发生中功能坐标。我们的初步数据显示了我们方法的可行性。我们预计，我们的研究将提供新的见解，对塑造立体膜的分子机制并确定其特性。很有可能，我们的发现可能将几个与死亡性相关的基因联系起来与一个共同的分子途径联系起来，并为开发治疗某些形式的疾病的治疗方法提供新的潜在客户。