Expanding the utility of Drosophila as a model for hearing research

扩大果蝇作为听力研究模型的用途

• 批准号: 7332275
• 负责人: GRACE E BOEKHOFF-FALK
• 金额: $ 14.14万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7332275
• 关键词: Achievement; Animal Model; Auditory; Auditory system; Biological; Biology; CCAAT displacement protein; Cell Cycle Regulation; Cellular biology; Defect; Development; Drosophila genus; Drosophila melanogaster; Gene Targeting; Genes; Genetic; Genetic Screening; Goals; Hearing; Hearing Impaired Persons; Homologous Gene; Human; Insecta; Investigation; Laboratories; Light; Maintenance; Mammals; Modeling; Nerve Degeneration; Organ; Pathway interactions; Proteins; Research; Structure; System; Techniques; Tumor Suppressor Proteins; Work; base; chromatin immunoprecipitation; deafness; developmental genetics; homeodomain; in vivo; innovation; insight; mutant; novel; research study; technique development; transcription factor

The goal of the research described in this proposal is to advance our understanding of fundamental biological mechanisms used to construct auditory and other mechanosensory systems. The experiments proposed here have two objectives. First, we plan to develop techniques that will be generally applicable to the investigation of auditory systems from insects to mammals. Second, we will use these techniques to study development and differentiation of the Drosophila (fruitfly) auditory organ. Together these experiments will expand the utility of Drosophila as a model for hearing research while providing insight into the differentiation and function of the Drosophila auditory organ. The experiments are focused the cut gene. We have shown that cut mutants are deaf and that their deafness is correlated both with defects in the mechanotransducing structures of the auditory organ and with neurodegeneration. The approaches used to date have provided only a partial picture of cut function with little insight into specific mechanisms of cut action. Here, I propose to develop and utilize an innovative and powerful combination of chromatin immunoprecipitation (ChIP) and microarray expression analysis to identify genes regulated by Cut.cut encodes an unusual homeodomain transcription factor whose human homolog, CCAAT-displacement protein (CDP)/CUTL1, has been implicated in cell cycle regulation and functions as a tumor suppressor. The proposed experiments will significantly expand our understanding of what Cut/CDP proteins do and how they do it. Fields that will be substantially impacted by these studies include: hearing, mechanosensation in general, Cut/CDP biology, and transcription factor biology. In light of the emerging developmental genetic parallels between Drosophila and vertebrate auditory organ development, I anticipate that information generated by the proposed experiments also will be relevant to human hearing.

本提案中所描述的研究目标是促进我们对基础知识的理解。 用于构建听觉和其他机械感觉系统的生物学机制。实验 这里提出的有两个目标。首先，我们计划开发技术，将普遍适用于 对从昆虫到哺乳动物的听觉系统的研究。其次，我们将使用这些技术来 研究果蝇听觉器官的发育和分化。这些实验 将扩大果蝇作为听力研究模型的实用性，同时提供对听力的深入了解。 果蝇听觉器官的分化和功能。实验主要集中在cut基因上。我们 已经表明，切割突变体是耳聋的，他们的耳聋与缺陷， 听觉器官的机械传导结构和神经变性。用于 数据只提供了切割功能的部分图像，对切割的具体机制知之甚少 行动上在这里，我建议开发和利用一种创新的和强大的染色质组合， 免疫沉淀（ChIP）和微阵列表达分析，以鉴定受切割调控的基因。 编码一种不寻常的同源域转录因子，其人类同源物CCAAT-置换 蛋白质（CDP）/CUTL1参与细胞周期调控并作为肿瘤抑制因子发挥作用。的 提出的实验将大大扩展我们对Cut/CDP蛋白质的作用以及它们如何作用的理解。 将受到这些研究重大影响的领域包括：听力，机械感觉， 一般，切割/CDP生物学和转录因子生物学。鉴于新兴的发育遗传学 果蝇和脊椎动物听觉器官发育的相似之处， 所提出的实验产生的声音也将与人类听觉有关。