Timothy J. Larson
Ph.D., Biochemistry, University of Texas Graduate School of Biomedical Sciences at Houston, 1978
B.S., Chemistry and Biology, Texas Lutheran University, 1973
1996 – present: Professor, Department of Biochemistry, Virginia Tech
1993 – 1994: Visiting Professor, Center for Molecular Biology, University of Heidelberg, Germany
1990-1996: Associate Professor, Department of Biochemistry, Virginia Tech
1986-1990: Assistant Professor, Department of Biochemistry, Virginia Tech
1983-1986: Assistant Professor, Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine, Grand Forks
1980-1982: Postdoctoral Research Associate, Department of Biology, University of Konstanz, Germany
1978-1979 & 1982-1983: Postdoctoral Research Associate, Department of Biochemistry, Duke University Medical Center, Durham NC
Selected Major Awards
1980 – 1981: Alexander von Humboldt Postdoctoral Fellow
1996 – 2000: National Institutes of Health Physiological Chemistry Study Section
BCHM 4124 – Laboratory Problems in Biochemistry and Molecular
BCHM 5984 – Prokaryotic and Eukaryotic Gene Regulation
BCHM 5054 – Prokaryotic Gene Regulation
Other Teaching and Advising
I have served (with David Bevan) as an undergraduate program director. We participate in coordinating summer orientation, registration of new biochemistry majors, screening of scholarship applications, visitation programs for students who have been offered admission, and college open house weekends.
I have served as Academic Advisor for one-half or one-third of the biochemistry majors in the classes of 1994, 1999, 2004, 2010, 2014 and 2016.
Genetic and biochemical approaches are being used to establish metabolic pathways involving sulfur metabolism in bacteria. Current focus is on the nitrogen fixing, obligate aerobe, Azotobacter vinelandii, whose natural habitat is the soil. Several different metabolic pathways are under investigation:
1. Biosynthesis of the thiazole ring of vitamin B1 (thiamin). One of the key enzymes for this pathway (encoded by thiF of most organisms) is not present among the proteins predicted by the genome sequence of A. vinelandii. We are testing the hypothesis that a protein similar in amino acid sequence to ThiF (MoeB1) participates in a similar enzymatic step for both the molybdopterin and thiamin biosynthetic pathways.
2. Proposed sulfur detoxification pathway. A. vinelandii has three genes predicted to encode sulfur dioxygenase. Two of these genes encode active sulfur dioxygenases, but the function of the third remains to be established. One of the genes is present in an operon predicted to encode two other genes involved in sulfur trafficking (sulfate or thiosulfate transporter, and rhodanese, a sulfurtransferase). Mutant strains deficient in each of these genes will be constructed, and phenotypes will be assessed.
3. Trafficking of sulfur by sulfurtransferases (rhodaneses). The genome sequences of most Eubacteria predict the presence of multiple proteins with a rhodanese domain. A. vinelandii is no exception, where 12 rhodanese-containing proteins are predicted. Two of these proteins are predicted to function in sulfur and selenium modification of tRNAs, but the physiological roles of the other ten are largely unknown. Further work on purification and characterization of these proteins is needed, along with characterization of mutant strains deficient in the respective genes.
Dahl, J. U., A. Urban, A. Bolte, P. Sirabhaya, J. L. Donahue, M. Nimtz, T. J. Larson, and S. Leimkuhler. 2011. The Identification of a novel protein involved in molybdenum cofactor biosynthesis in Escherichia coli. J. Biol. Chem. 286:35801-35812.
Riboldi, G. P., T. J. Larson, and J. Frazzon. 2011. Enterococcus faecalis sufCDSUB complements Escherichia coli sufABCDSE. FEMS Microbiol. Lett. 320:15-24.
Setubal, J. C., P. Dos Santos, B. S. Goldman, H. Ertesvag, G. Espin, L. M. Rubio, S. Valla, N. F. Almeida, D. Balasubramanian, L. Cromes, L. Curatti, Z. Du, E. Godsy, B. Goodner, K. Hellner-Burris, J. A. Hernandez, K. Houmiel, J. Imperial, C. Kennedy, T. J. Larson, P. Latreille, L. S. Ligon, J. Lu, M. Maerk, N. M. Miller, S. Norton, I. P. O'Carroll, I. Paulsen, E. C. Raulfs, R. Roemer, J. Rosser, D. Segura, S. Slater, S. L. Stricklin, D. J. Studholme, J. Sun, C. J. Viana, E. Wallin, B. Wang, C. Wheeler, H. Zhu, D. R. Dean, R. Dixon, and D. Wood. 2009. The genome sequence of Azotobacter vinelandii, an obligate aerobe specialized to support diverse anaerobic metabolic processes. J. Bacteriol. 191:4534-4545.
Cheng, H., J. Donahue, S. Battle, W. K. Ray and T. J. Larson. 2008. Biochemical and genetic characterization of PspE and GlpE, two single-domain sulfurtransferases of Escherichia coli. The Open Microbiol. J. 2:18-28.
Wolfe,M. D., F. Ahmed, G. M. Lacourciere, T. C. Stadtman, C. T. Lauhon and T. J. Larson. 2004. Functional diversity of the rhodanese homology domain: the Escherichia coli ybbB gene encodes a selenophosphate-dependent tRNA 2-selenouridine synthase. J. Biol. Chem. 279:1801-1809.
Spallarossa, A., J. L. Donahue, T. J. Larson, M. Bolognesi and D. Bordo. 2001. Escherichia coli GlpE is a prototype sulfurtransferase for the single-domain rhodanese homology superfamily. Structure 9:1117-1125.
Ray, W. K., G. Zeng, M. B. Potters, A. M. Mansuri and T. J. Larson. 2000. Characterization of a 12-kilodalton rhodanese encoded by glpE of Escherichia coli and its interaction with thioredoxin. J. Bacteriol. 182:2277-2284.
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