The Molecular Biology of Neurosurgery Systems

描述（由申请人提供）：神经感觉功能的丧失，特别是听觉和视觉的丧失，对交流、教育、职业和生活质量造成了毁灭性的影响。由于内耳和视网膜的神经感觉细胞在受损或退化后不能被替换，因此这种损失是永久性的。内布拉斯加州神经感觉系统分子生物学中心的目的是表征控制神经感觉功能发展和维持的遗传机制，以及与相关基因突变相关的相应病理，以确定潜在的干预途径。我们将专注于有前途的再生医学策略，如通过使用多能干细胞或内耳和视网膜有丝分裂后细胞的去分化和再生来重建受损细胞。这些研究利用专门的动物模型，允许在发育的特定关键点控制基因表达，并在分子和表型水平上详细评估相关发现。为了促进这些研究，3个独立研究机构联合建立了一个互动中心，采用多学科方法，旨在实现这些明确的目标。我们以3名资深研究人员为核心，并建立了一个示范性的外部咨询委员会，成功地指导了14名初级教师，并通过类似的主题和机制方法建立了一个合作小组。我们的研究有三个科学核心：一个用于开发小鼠模型的小鼠基因组工程核心，一个用于全面评估基因表达水平和确定可能的遗传网络的微阵列核心，以及一个用于研究实验改变结果的分子表型/组织学核心。这些核心是对所有三个机构的研究基础设施的重要补充。在COBRE项目的第二阶段，我们将继续支持6名初级研究人员：2名研究失明和聋哑/失明特定综合征的机制，1名专注于视网膜干细胞群体的发育和富集，3名研究内耳分化的分子途径，以促进感觉再生。当这些项目获得外部资金并从中心资金中轮换时，将增加新的项目。增加新的研究人员，以及继续支持研究活动和核心设施的运作，将确保不断增长的“临界质量”合作，这将维持该中心，并使参与者能够获得外部资金，这将确保其长期生存。

DESCRIPTION (provided by applicant): The loss of neurosensory function, particularly the sensations of hearing and vision has devastating affects on communication, education, occupation, and quality of life. Since neurosensory cells of the inner ear and retina are not replaced after damage or degeneration, such losses are permanent. The purpose of the Nebraska Center for the Molecular Biology of Neurosensory Systems is to characterize the genetic mechanisms controlling the development and maintenance of neurosensory functions and the corresponding pathology associated with relevant gene mutations to identify potential avenues for intervention. We will focus our efforts on promising regenerative medicine strategies such as the reconstitution of damaged cells through the use of pluripotent stem cells or de-differentiation and regeneration of post-mitotic cells in the inner ear and retina. These studies utilize specialized animal models that allow control of gene expression at specific critical points in development, with detailed evaluation of the associated findings at the molecular and phenotypic levels. To facilitate these studies, 3 independent research institutions have joined to build an interactive Center with a multidisciplinary approach designed to address to these well-defined objectives. With a core of 3 senior researchers and an exemplary External Advisory Committee, we have successfully mentored 14 junior faculty members and created a collaborative group united by similar thematic and mechanistic approaches. Our research has been facilitated by 3 scientific cores: a Mouse Genome Engineering core for the development of mouse models, a Microarray core for comprehensive assessment of gene expression levels and determination of possible genetic networks, and a Molecular Phenotyping/Histology core to study the results of experimental alterations. These cores are an important addition to the research infrastructure of all 3 institutions. In the second phase of this COBRE project, we will continue to support 6 junior researchers: 2 are studying the mechanisms of specific syndromes of blindness and deaf/blindness, 1 is concentrating on the development and enrichment of retinal stem cell populations, and 3 are studying the molecular pathways of inner ear differentiation with the goal of facilitating sensory regeneration. As those projects obtain external funding and rotate off Center funding, new projects will be added. The addition of new investigators, along with continued support of research activities and the operation of core facilities, will ensure a growing "critical mass" of collaboration that will sustain the Center, and enable participants to obtain external funding which will ensure its long term viability. PUBLIC HEALTH RELEVANCE (provided by applicant): The loss of sensory abilities such as hearing and vision causes devastating affects on communication, education, occupation, and quality of life. Once mature sensory cells of the eye or ear are lost, they are not replaced, so that these losses have been permanent. By studying the genetic controls of development of the sensory cells in the retina and inner ear, the scientists in this Center will determine optimal approaches for therapies utilizing precursor cells that can develop into replacement cells and restore function.