The Molecular Biology of Neurosurgery Systems

神经外科系统的分子生物学

• 批准号: 7928801
• 负责人: Shelley D Smith
• 金额: $ 214.77万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7928801
• 关键词: Address; Advisory Committees; Affect; Animal Model; Animals; Arts; Biological Models; Blindness; Cell Nucleus; Cells; Centers of Research Excellence; Clinical Research; Collaborations; Communication; Communities; Complement; Core Facility; Critiques; Data; Development; Disease; Ear; Education; Ensure; Equilibrium; Esthesia; Evaluation; Eye; Eye Development; Faculty; Funding; Funding Mechanisms; Gene Expression; Gene Mutation; Genes; Genetic; Genome engineering; Goals; Growth; Hearing; Hearing Impaired Persons; Histology; In Vitro; Institution; Intervention; Investigation; Laboratories; Labyrinth; Maintenance; Mentors; Methodology; Mitotic; Molecular; Molecular Biology; Molecular Genetics; Natural regeneration; Nebraska; Occupations; Participant; Pathogenesis; Pathology; Pathway interactions; Peer Review; Phase; Pluripotent Stem Cells; Postdoctoral Fellow; Publications; Quality of life; Regenerative Medicine; Research; Research Activity; Research Infrastructure; Research Personnel; Research Project Grants; Retina; Role; Scientist; Sensory; Services; Structure; Syndrome; System; Vision; career; cell injury; clinically significant; design; experience; functional restoration; graduate student; improved; innovation; interdisciplinary approach; interest; loss of function; member; molecular phenotype; mouse genome; mouse model; neurosurgery; operation; precursor cell; prevent; programs; public health relevance; reconstitution; research and development; retinal progenitor cell; stem cell population; tissue culture; tool

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.

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感觉，对沟通，教育，职业和生活质量具有破坏性影响。由于内耳和视网膜的神经感觉细胞在损伤或变性后不会被替换，因此这种损失是永久性的。内布拉斯加神经感觉系统分子生物学中心的目的是描述控制神经感觉功能发育和维持的遗传机制以及与相关基因突变相关的相应病理学，以确定潜在的干预途径。我们将把精力集中在有前途的再生医学策略上，例如通过使用多能干细胞或内耳和视网膜中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个独立的研究机构已加入建立一个互动中心，旨在解决这些明确的目标，多学科的方法。凭借3名高级研究人员和一个模范的外部咨询委员会的核心，我们已经成功地指导了14名初级教师，并创建了一个由类似的主题和机械方法联合起来的协作小组。我们的研究得到了3个科学核心的促进：用于开发小鼠模型的小鼠基因组工程核心，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3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名正在研究盲和聋/盲的特定综合征的机制，1名专注于视网膜干细胞群的发育和富集，3名正在研究内耳分化的分子途径，目标是促进感觉再生。随着这些项目获得外部资金并轮换中心资金，将添加新项目。增加新的调查人员，沿着继续支持研究活动和核心设施的运作，将确保不断增长的合作“临界质量”，以维持中心，并使参与者能够获得外部资金，以确保其长期生存能力。 公共卫生相关性（由申请人提供）：听觉和视觉等感官能力的丧失会对沟通、教育、职业和生活质量造成破坏性影响。一旦眼睛或耳朵的成熟感觉细胞丢失，它们就不会被替换，因此这些损失是永久性的。通过研究视网膜和内耳感觉细胞发育的遗传控制，该中心的科学家将确定利用前体细胞进行治疗的最佳方法，这些前体细胞可以发育成替代细胞并恢复功能。