MECHANISMS OF INHERITED MEMBRANE TRANSPORT DISORDERS

该计划旨在阐明潜在的异常， 氨基酸和糖的无序转运， 胱氨酸尿症是典型的遗传性转运异常， 与几种遗传性代谢相关的范可尼综合征 疾病与其全球混乱的溶质运输系统， 未成熟氨基酸尿症的个体发生事件。 程序 将利用细胞和亚细胞系统以及完整的 动物模型来描述所涉及的基本分子事件， 将专注于尖端方法的应用，如 质谱、核磁共振和DNA技术， 运输事件。 该研究计划由六个项目组成， 它们的主题目标相互关联，工作人员相互联系， 技术和三个核心。 这些措施是： 项目1，胱氨酸尿症和肾脏胱氨酸-赖氨酸的性质 运输系统，西格尔博士，项目2的主要研究员， 范可尼综合征化学模型的~（15）N-GC-MS研究 和13 C-NMR，主要研究者，Nissim博士，项目3， 培养的肾上皮细胞作为肾脏转运的模型系统 机制，主要研究者，Dr. States，项目4，动物 运输障碍模型，首席研究员，Drs. Bovee 和Segal，项目5，人体肠道氨基酸的检查 运输系统，麦克纳马拉博士，项目6，个体发育和调节 肾膜转运，许博士，核心A，膜和 小管制备，McNamara博士，核心B分析 色谱法，Yandrasitz博士和核心C，行政， 西格尔

The program aims to elucidate the underlying abnormalities in deranged transport of amino acids and sugar with emphasis on cystinuria as the prototypic inherited transport abnormality, the Fanconi syndrome associated with several inherited metabolic diseases with its global disarray of solute transport systems and ontogenic events of the aminoaciduria of immaturity. The program will utilize cellular and subcellular systems as well as intact animal models to delineate the basic molecular events involved and will be focused on the application of cutting-edge methods such as mass spectrometry and NMR and DNA technology, to examine cellular transport events. The proposed research program consists of six projects all interrelated by their thematic aim, interlocking staff and shared techniques and three cores. These are: Project 1, Cystinuria and the Nature of the Renal Cystine-Lysine Transport System, Dr. Segal, Principal Investigator, Project 2, Chemical Models of the Fanconi Syndrome: Studies with 15N-GC-MS and 13C-NMR, Principal Investigator, Dr. Nissim, Project 3, Cultured Renal Epithelial Cells as Model Systems of Renal Transport Mechanisms, Principal Investigator, Dr. States, Project 4, Animal Models of Transport Disorders, Principal Investigator, Drs. Bovee and Segal, Project 5, Examination of Human Intestinal Amino Acid Transport Systems, Dr. McNamara, Project 6, Ontogeny and Regulation of Transport in Renal Membranes, Dr. Hsu, Core A, Membrane and Tubule Preparation, Dr. McNamara, Core B Analytical Chromatography., Dr. Yandrasitz, and Core C, Administrative, Dr. Segal.