Cellular and Molecular Studies of Renal Transport

肾脏运输的细胞和分子研究

• 批准号: 8328730
• 负责人: Michael J. Caplan
• 金额: $ 111.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-12-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8328730
• 关键词: Address; American Heart Association; Animals; Award; Biological Assay; Biophysics; Books; Boron; Carrier Proteins; Cell Culture Techniques; Cell membrane; Cells; Clinical; Collaborations; Commit; Computer software; Confocal Microscopy; Core Facility; Coupled; Development Plans; Disease; Distal; Electrolytes; Energy Metabolism; Epithelial; Equipment; Faculty; Fostering; Funding; Gene Targeting; Generations; Genetic; Goals; Health; Homeostasis; Hypertension; Image; Immune; In Vitro; Individual; Institute of Medicine (U.S.); International; Ions; Joints; Kidney; Laboratories; Leadership; Light; Liquid substance; Mammalian Cell; Medical; Medicine; Methods; Micropuncture; Microscope; Microscopy; Molecular; Molecular Cloning; Mus; Mutagenesis; Operative Surgical Procedures; Organ; Oryctolagus cuniculus; Paraffin; Patch-Clamp Techniques; Pathogenesis; Pathway interactions; Perfusion; Phosphopeptides; Phosphorylation Site; Physiological; Physiology; Play; Positioning Attribute; Preparation; Problem Solving; Process; Productivity; Program Research Project Grants; Proteins; Publishing; Rattus; Recording of previous events; Regulation; Relative (related person); Renal function; Renal tubule structure; Research; Research Personnel; Research Project Grants; Role; Scientist; Secure; Services; Sodium Chloride; System; Techniques; Textbooks; Tissue Fixation; Tissue Stains; Transgenic Mice; United States National Academy of Sciences; Universities; Update; Vesicle; Work; Xenopus oocyte; base; cDNA Expression; cytochemistry; experience; fluorescence imaging; genetic regulatory protein; gratitude; in vivo; insight; interest; kidney cell; medical schools; member; mouse development; patch clamp; professor; programs; protein transport; solute; tissue culture; tool

DESCRIPTION, OVERALL (provided by applicant): The overall goal of this Program Project is to understand the mechanisms underlying renal fluid and electrolyte homeostasis and renal epithelial function in health and the processes that modulate these mechanisms in disease. A broad spectrum of techniques will be used 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 the intact tubule, the organ, and the whole animal. Our strategy to pursue these themes successfully will include close collaboration on interrelated research projects; sharing of expertise, concepts and techniques by Directors of the five individual Projects and the four research Cores; joint use of the research core facilities and single administrative core. The research projects comprise a broad range of experimental preparations including ion/solute transport proteins, transport regulatory proteins, transfected mammalian cells in tissue culture, isolated cell membrane vesicles, Xenopus oocyte expression system, isolated kidney cells and tubules, and whole kidney in vivo. We shall use a wide range of methods including molecular cloning and mutagenesis, functional cDNA expression, generation and use of transgenic mice, immune-cytochemistry, phosphopeptide enrichment coupled to mass spectral identification of phosphorylation sites, confocal microscopy, fluorometric assays of cell ion activities, whole cell clamp and patch- and giant patch-clamp techniques, in vivo and in vitro perfusion of defined tubule segments, and clearance studies. Each of the projects and cores is concerned with the central themes of the Program: to provide important new insights into individual transport proteins that play a role in renal electrolyte homeostasis, to elucidate the regulation of these transport-related proteins, to elucidate the cellular pathways involved in epithelial polarity that is an absolute prerequisite for vectorial solute and fluid transport, and to assess the relative contributions of these proteins to tubule and organ function under conditions of normal and deranged electrolyte and energy metabolism. Our strategy to pursue these themes successfully will include close collaboration on interrelated research projects; sharing of expertise, concepts and techniques by Program investigators; and joint use of core facilities.

总体描述（由申请人提供）：