Richard L. Weiss, Ph.D.

Work Address:
Young Hall 5072A
Mail Code: 156905

Affiliations
Affiliations
Lab Director, R. Weiss Lab
Professor, Chemistry and Biochemistry, Biochemistry, Molecular Biology
Member, Graduate Program in Biochemistry, Molecular and Structural Biology, Molecular Biology Institute
Researcher, Biochemistry, Chemical Biology
Research Interests
The major focus of our laboratory 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 are investigating the metabolic consequences of relocating the arginine biosynthetic enzymes from the mitochondrial matrix to the cytosol: structural genes are being altered so that their products are no longer translocated into the mitochondria; the physiological consequences of such enzyme mislocation is being examined. We are also examining how variations in cytosolic arginine concentrations are communicated across the mitochondrial membranes to coordinately inhibit two enzymes of arginine biosynthesis: cell biology techniques are being used to identify and characterize transport systems in intracellular (organellar) membranes and 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. Initial results suggest the existence of multiple promoters and products from a single gene which are expressed under different conditions. The results of these research projects will provide insight into the function of enzyme and amino acid compartmentation in eukaryotic cells.
Biography:

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

Publications
Barbieri John S, Weiss Richard L Collapse of aortic tube graft during systole. Echocardiography (Mount Kisco, N.Y.). 2013; 30(4): E108-9.
Ferrari Giovanni, Sainger Rachana, Beckmann Erik, Keller Gianluca, Yu Pey-Jen, Monti Maria Cristina, Galloway Aubrey C, Weiss Richard L, Vernick William, Grau Juan B Validation of plasma biomarkers in degenerative calcific aortic stenosis. The Journal of surgical research. 2010; 163(1): 12-7.
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.
Parra-Gessert L, Koo K, Fajardo J, Weiss R L Processing and function of a polyprotein precursor of two mitochondrial proteins in neurospora crassa. J. Biol. Chem. 1998; 273(14): 7972-80.
Keenan K A, Weiss R L Characterization of vacuolar arginine uptake and amino acid efflux in Neurospora crassa using cupric ion to permeabilize the plasma membrane. Fungal Genet. Biol. 1997; 22(3): 177-90.
Yu Y G, Turner G E, Weiss R L Acetylglutamate synthase from Neurospora crassa: structure and regulation of expression. Mol. Microbiol. 1996; 22(3): 545-54.
Kim, J. H. and Weiss, R. L. Genetic Analysis of Interactions between arg-14 and arg-6 Gene Products in Neurospora crassa. Mol. Cells. 1995; 5: 461-466.
Gessert S F, Kim J H, Nargang F E, Weiss R L A polyprotein precursor of two mitochondrial enzymes in Neurospora crassa. Gene structure and precursor processing. J. Biol. Chem. 1994; 269(11): 8189-203.
Yu Y G, Weiss R L Arginine transport in mitochondria of Neurospora crassa. J. Biol. Chem. 1992; 267(22): 15491-5.
Kanamori K, Weiss R L, Roberts J D Efficiency factors and ATP/ADP ratios in nitrogen-fixing Bacillus polymyxa and Bacillus azotofixans. J. Bacteriol. 1990; 172(4): 1962-8.
Kanamori K, Weiss R L, Roberts J D Ammonia assimilation pathways in nitrogen-fixing Clostridium kluyverii and Clostridium butyricum. J. Bacteriol. 1989; 171(4): 2148-54.
Paek Y L, Weiss R L Identification of an arginine carrier in the vacuolar membrane of Neurospora crassa. J. Biol. Chem. 1989; 264(13): 7285-90.
Davis R H, Weiss R L Novel mechanisms controlling arginine metabolism in Neurospora. Trends Biochem. Sci. 1988; 13(3): 101-4.