DISSECTING THE EAR NEUROSENSORY DEVELOPMENT.

剖析耳朵神经感觉发育。

• 批准号: 7809961
• 负责人: BERND FRITZSCH
• 金额: $ 35.77万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-09 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7809961
• 关键词: Ambystoma; Amendment; Animals; Candidate Disease Gene; Cell Differentiation process; Cell Proliferation; Computer Simulation; Data; Data Analyses; Development; Ear; Faculty; Funding; Future; Gene Expression; Genes; Goals; Grant; Hair Cells; Housekeeping Gene; In Situ Hybridization; Iowa; Messenger RNA; Molecular Profiling; Mus; National Institute on Deafness and Other Communication Disorders; Natural regeneration; Organ; Postdoctoral Fellow; Preparation; Public Health; Research Personnel; Resources; Running; Skin; Time; Translational Research; Unemployment; Universities; data mining; gene discovery; mouse development; neuromast; new technology; novel; parent grant; public health relevance; skills

DESCRIPTION (provided by applicant): The application is targeted to hire a postdoc that would be unemployed starting July 1st 2009 and to expand the number of PIs by adding two new faculty to the portfolio of investigators to accomplish a new scientific objective. In addition, the revision will to generate novel resources that were impossible to generate at the time of the application of the parent grant but are now feasible due to technological advances. We propose to subcontract two investigators for those specific skills needed to accomplish the new aim 4 added to our previously funded grant. Building on new technology recently purchased at the University of Iowa as well as advances in data mining allowing gene identification in animals that have not been sequenced as yet makes the proposed competitive amendment a logical expansion of our funded project. Aim 4: We will identify genes uniquely associated with mechanosensory development by employing an in silico subtraction of neuromast, ampullary organ and skin expressed genes to isolate those genes. Technically, the project consists of several steps, isolation and preparation of neuromast and ampullary organ mRNA, linear amplification and pyrosequencing using 454 sequencers, data analysis and verification of expression profiles using in situ hybridization. The data resulting from the 454 runs will be used for in silico subtraction of general housekeeping genes for skin and ampullary organ development to reduce the genes exclusively to mechanosensory neuromast and hair cell development. Probes will be generated for candidate genes and the expression will be assessed using in situ hybridization. This approach will identify genes associated with mechanosensory hair cell proliferation, specification and differentiation. Verification of gene expression will allow correlating genes with different states of mechanosensory hair cell differentiation. PUBLIC HEALTH RELEVANCE: Regenerating hair cells is a major goal of NIDCD. To this end, we will extract genes relevant for the continuous proliferation and differentiation of mechanosensory hair cells in the axolotl to direct future attempts for such regeneration in the mouse. Verifying the function of those newly discovered genes in mouse development will greatly enhance our ability to move the already funded R01 project toward translational research.

描述（由申请人提供）：申请旨在雇用从2009年7月1日开始失业的博士后，并通过向调查人员的投资组合添加两个新教师来扩大PI的数量，以实现一个新的科学目标。此外，修订将产生新的资源，这些资源在应用父母赠款时不可能产生，但由于技术进步，现在是可行的。我们建议将两名调查人员分包，以实现我们以前资助的赠款中完成新目标4所需的特定技能。以新技术为基础，最近在爱荷华大学购买了新技术，以及数据挖掘的进步，允许在尚未测序的动物中识别基因识别，这使得拟议的竞争修正案成为我们资助的项目的逻辑扩展。 AIM 4：我们将通过使用神经光的硅缩减，截肢器官和皮肤表达的基因来隔离这些基因来识别与机械增强发育相关的基因。从技术上讲，该项目包括多个步骤，即神经瘤和隔离器官mRNA的隔离和制备，使用454个测序仪，使用原位杂交对表达谱进行了线性扩增和焦磷酸测序。由454次运行产生的数据将用于用于皮肤和隔膜器官发育的一般管家基因的计算机减法，以将基因专门降低到机械感应神经瘤和毛细胞的发育中。探针将用于候选基因，并将使用原位杂交评估表达。这种方法将确定与机械感知性毛细胞增殖，规范和分化相关的基因。基因表达的验证将允许将基因与不同状态的机械感觉毛细胞分化相关。 公共卫生相关性：再生毛细胞是NIDCD的主要目标。为此，我们将提取与Axolotl中机械感知毛细胞的连续增殖和分化有关的基因，以指导将来的小鼠再生尝试。验证那些新发现的基因在小鼠发育中的功能将极大地增强我们将已经资助的R01项目转向转化研究的能力。