Cellular and Molecular Studies of Renal Transport

描述（申请人提供）：体液的成分和体积由肾脏决定。因此，肾脏感知、响应和调节尿液成分的机制构成了身体控制其内部环境的主要途径。这些机制在人类健康中的核心重要性是恰当地说明了其扰动的病理生理后果。肾脏液体和电解质转运调节的障碍导致各种严重和常见的疾病。为了了解尿液的成分以及体液的成分是如何确定的，有必要对所有的 这些过程。确定转运蛋白和细胞旁途径性质的细胞和分子机制至关重要。此外，有必要阐明控制这些调节过程的细胞机制。 正如我们整个历史一样，本计划项目的总体目标是了解 肾液、电解质和大分子转运的潜在机制。为此，我们使用广泛的技术来解决一系列问题，从单个转运相关蛋白的分子特征到这些蛋白在单细胞、完整肾小管、肾脏和整个动物水平上对综合肾功能的贡献。这些项目的具体目标共同构成了一个协作和协同努力，以确定调节肾脏转运多个方面的机制。没有一段肾小管和它所介导的转运过程是孤立的。通过同时探索几个运输过程，并通过各种协作方法，我们将能够对这些复杂的相互关系产生新的见解。只有通过这种协调的努力，才能对肾功能有系统的了解。

DESCRIPTION (provided by applicant): The composition and volume of the body fluid are determined by the kidney. Thus, the mechanisms through which the kidney senses, responds to and adjusts the composition of the forming urine constitute the principal pathways through which the body controls its internal environment. The central importance of these mechanisms in human health is aptly illustrated by the pathophysiological consequences of their perturbation. Breakdowns in the regulation of renal fluid and electrolyte transport result in a wide variety of serious and common conditions. In order to understand how the composition of the urine, and thus of the body fluid is determined, it is necessary to develop a holistic understanding of all of these processes. It is critical to identify the cellular and molecular mechanisms through which the properties of transport proteins and of the paracellular pathway are determined. In addition, it is necessary to elucidate the cellular machinery that controls these regulatory processes. As has been true for our entire history, the overall goal of this Program Project is to understand the mechanisms underlying renal fluid, electrolyte and macromolecule transport. Towards this end, we use a broad spectrum of techniques to address a continuum of problems ranging from the molecular characterization of individual transport-related proteins to the contribution of these proteins to integrated renal function at the level of single cells, intact tubules, the kidney, andthe whole animal. The specific objectives of these projects together constitute a collaborative and synergistic effort to define the mechanisms that regulate multiple aspects of renal transport. No segment of the renal tubule and none of the transport processes that it mediates work in isolation. By exploring several transport processes simultaneously and through a variety of collaborative approaches, we will be able to generate new insights into these complex inter-relationships. It is only through such a coordinated effort that a systematic understanding of renal function can be generated.