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PROTEINS OF ORGAN OF CORTI AND SURROUNDING FLUIDS

PROTEINS OF ORGAN OF CORTI AND SURROUNDING FLUIDS
柯蒂氏器官和周围液体的蛋白质
批准号:
3218095
负责人:
RUEDIGER R THALMANN
金额:
$32.34万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
1992
资助国家:
美国
项目状态:
已结题
起止时间:
1992-09-01 至 1995-08-31

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中文摘要
翻译
耳朵将声脉冲转换成高等可解释的信号 中锋。精致的声乐乐器,科尔蒂(0C)的管风琴 由具有所有敏感性的活细胞组成。大多数功能障碍 是由化学物质介导的,出于医学原因,它 迫切需要阐明这些生物化学之谜。这项建议 考虑两种蛋白质(OCPI)的生物化学和分子生物学 和OCP2)存在于极高的0C中的未知功能 浓度。数量庞大,表现局限于内心 耳朵,并在耳蜗开始表达的时候显著增加 功能暗示在试听中起着重要的作用。这规定了一个 积极的跨学科方法来阐明它们的功能。我们 将应用蛋白质化学的标准技术,以适应微观 水平。初级氨基酸序列的分析将利用最近的 技术进步。细胞和亚细胞定位通过 免疫组织化学技术将提供有关 它们的功能。标准克隆技术将提供基本的 对OCP的结构和功能的洞察。更重要的是, 拟议的mRNA表达实验使用OCP作为工具来获得 关于内耳发育的重要信息。克隆人0CP 基因为它们提供了内耳疾病的候选基因。大号 关于这些项目的大量初步信息使他们很高 优先、低风险。可以说,OC驻留在组织培养中, 被完全不同的化学成分的液体包围着 电极化。对……构成的准确定义 这些液体至关重要。我们设计了复杂的 化学物质测定中避免伪影的技术 外淋巴的成分。我们将确定有效的浓度 大量的小分子,并建立全面的蛋白质图谱。 大多数伪影是由于脑脊液(CSF)的流入 耳囊是穿孔的,用于标本取样或 电极的插入。脑脊液的流入可能会损害0C,因为它 导致氨基酸水平非常低,蛋白质含量低,以及其他 潜在的后遗症。这种情况也存在于外淋巴瘘中, 并可能导致听力障碍。我们的研究也是 致力于外淋巴或疾病特异性蛋白的研究,并将 批判性评价鼓阶外淋巴来源于 从脑脊液中大量提取。
英文摘要
The ear converts acoustic impulses into signals interpretable by higher centers. The delicate acoustic instrument, the organ of Corti (0C) is made of living cells with all their susceptibilities. Most dysfunctions of the ear are mediated chemically, and for medical reasons, it is Imperative that these biochemical mysteries be elucidated. This proposal considers the biochemistry and molecular biology of two proteins (OCPI and OCP2) of unknown function present in the 0C at exceedingly high concentrations. The large amounts, expression restricted to the inner ear, and major increase in expression at the time the cochlea begins to function imply an important role in audition. This dictates an aggressive interdisciplinary approach to elucidate their function. We will apply standard techniques of protein chemistry adapted to the micro level. Analysis of primary amino acid sequence will exploit recent technological advances. Cellular and subcellular localization by immunohistochemical techniques will provide indirect information about their function. Standard cloning techniques will provide fundamental insights into structure and function of the OCPs. More importantly, the proposed mRNA expression experiments use OCPs as a tool to obtain important information about inner ear development. Cloning human 0CP genes provides them as candidate genes for inner ear disease. A large body of preliminary information on these projects makes them high priority and low risk. The 0C resides in tissue culture, as it were, surrounded by fluids of fundamentally different chemical makeup and electrical polarization. A precise definition of the composition of these fluids is of paramount importance. We have designed sophisticated techniques to avoid artifacts in the determination of the chemical composition of perilymph. We will determine valid concentrations of numerous small molecules and establish comprehensive protein profiles. Most artifacts are due to influx of cerebrospinal fluid (CSF) whenever the otic capsule is perforated, either for the sampling of specimens or insertion of electrodes. The influx of CSF may damage the 0C, since it results in very low levels of amino acids, low protein, and other potential sequelae. This situation also exists in perilymph fistulae, and may contribute to the disturbance of hearing. Our studies are also geared to the study of perilymph- or disease-specific proteins, and will critically evaluate the claim that perilymph of scala tympani is derived in bulk from CSF.
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Molecular Characterization of Key Proteins Directing Otoconial Mineralization
  • 批准号:
    8460865
  • 项目类别:
  • 资助金额:
    $36.7万
  • 财政年份:
    2011
  • 负责人:
    RUEDIGER R THALMANN
  • 依托单位:
Molecular Characterization of Key Proteins Directing Otoconial Mineralization
  • 批准号:
    8263376
  • 项目类别:
  • 资助金额:
    $39.54万
  • 财政年份:
    2011
  • 负责人:
    RUEDIGER R THALMANN
  • 依托单位:
Molecular Characterization of Key Proteins Directing Otoconial Mineralization
  • 批准号:
    8086834
  • 项目类别:
  • 资助金额:
    $40.88万
  • 财政年份:
    2011
  • 负责人:
    RUEDIGER R THALMANN
  • 依托单位:
INTERPLAY OF BIOLOGICAL AND PHYSICAL PROCESSES IN OTOCONIAL MORPHOGENESIS
  • 批准号:
    7640829
  • 项目类别:
  • 资助金额:
    $19.0万
  • 财政年份:
    2008
  • 负责人:
    RUEDIGER R THALMANN
  • 依托单位:
海外基金