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.
