个人简介

Dr. Weiss received his B.S. from Stanford University and his Ph.D. from the University of Washington.

研究领域

Biochemistry/Metabolism/Aging and Development/Chemical Biology/Systems Biology and Biological Regulation

Metabolic Compartmentation in Neurospora Our major focus is to understand the role of compartmentation of enzymes and metabolites in biological regulation. The organellar localization of metabolic pathways requires considerable expenditure of metabolic energy for protein targeting, organelle assembly, and movement of substrates and products across intracellular membranes. Such expenditures must result in biological efficiencies commensurate with the investment of biological resources. However, it is not always clear what advantages are conferred by such compartmentation. We have focused our attention on arginine metabolism in Neurospora crassa because it encompasses many of the compartmental features characteristic of eukaryotic cells. Biosynthesis of arginine originates in the mitochondria but culminates in the cytosol. Intermediates and arginine cross both mitochondrial membranes. More than 95% of the intramycelial pool of arginine is sequestered in the vacuoles. Our hypothesis is that these compartmentation features play a significant role in the biology of the organism. We have investigated the metabolic consequences of relocating the arginine biosynthetic enzymes from the mitochondrial matrix to the cytosol. In addition, we have examined how variations in cytosolic arginine concentrations are communicated across the mitochondrial membranes to coordinately inhibit two enzymes of arginine biosynthesis. Molecular techniques are being used to construct mutants defective in the movement of metabolites across intracellular membranes. Control of arginine degradation is being examined by characterizing the expression, structure and properties of arginase, the initial catabolic enzyme. The results of these experiments will provide insight into the function of enzyme and amino acid compartmentation in eukaryotic cells.

近期论文

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Dunlap Jay C, Borkovich Katherine A, Henn Matthew R, Turner Gloria E, Sachs Matthew S, Glass N Louise, McCluskey Kevin, Plamann Michael, Galagan James E, Birren Bruce W, Weiss Richard L, Townsend Jeffrey P, Loros Jennifer J, Nelson Mary Anne, Lambreghts Randy, Colot Hildur V, Park Gyungsoon, Collopy Patrick, Ringelberg Carol, Crew Christopher, Litvinkova Liubov, DeCaprio Dave, Hood Heather M, Curilla Susan, Shi Mi, Crawford Matthew, Koerhsen Michael, Montgomery Phil, Larson Lisa, Pearson Matthew, Kasuga Takao, Tian Chaoguang, Basturkmen Meray, Altamirano Lorena, Xu Junhuan Enabling a community to dissect an organism: overview of the Neurospora functional genomics project. Adv. Genet., 2007; 57(2): 49-96. Colot Hildur V, Park Gyungsoon, Turner Gloria E, Ringelberg Carol, Crew Christopher M, Litvinkova Liubov, Weiss Richard L, Borkovich Katherine A, Dunlap Jay C A high-throughput gene knockout procedure for Neurospora reveals functions for multiple transcription factors. Proc. Natl. Acad. Sci. U.S.A., 2006; 103(27): 10352-7. Turner Gloria Ellen, Weiss Richard L Developmental expression of two forms of arginase in Neurospora crassa. Biochim. Biophys. Acta, 2006; 1760(6): 848-57. Borkovich Katherine A, Alex Lisa A, Yarden Oded, Freitag Michael, Turner Gloria E, Read Nick D, Seiler Stephan, Bell-Pedersen Deborah, Paietta John, Plesofsky Nora, Plamann Michael, Goodrich-Tanrikulu Marta, Schulte Ulrich, Mannhaupt Gertrud, Nargang Frank E, Radford Alan, Selitrennikoff Claude, Galagan James E, Dunlap Jay C, Loros Jennifer J, Catcheside David, Inoue Hirokazu, Aramayo Rodolfo, Polymenis Michael, Selker Eric U, Sachs Matthew S, Marzluf George A, Paulsen Ian, Davis Rowland, Ebbole Daniel J, Zelter Alex, Kalkman Eric R, O'Rourke Rebecca, Bowring Frederick, Yeadon Jane, Ishii Chizu, Suzuki Keiichiro, Sakai Wataru, Pratt Robert Lessons from the genome sequence of Neurospora crassa: tracing the path from genomic blueprint to multicellular organism. Microbiol. Mol. Biol. Rev., 2004; 68(1): 1-108. Marathe S, Yu Y G, Turner G E, Palmier C, Weiss R L Multiple forms of arginase are differentially expressed from a single locus in Neurospora crassa. J. Biol. Chem., 1998; 273(45): 29776-85.