Robert L Switzer
318D Roger Adams Lab
Office: (217) 333-3940
Lab: (217) 333-7098
Fax: (217) 244-5858
Mail to: Department of Biochemistry
419 Roger Adams Lab B-4
600 S Mathews Ave
Urbana, IL 61801
Professor Emeritus of Biochemistry
B.S. 1961 Univ. of Illinois, U-C
Ph.D. 1966 Univ. of California, Berkeley
Postdoc. 1966-68 Lab. of Biochemistry, Nat'l. Heart Institute, Nat'l. Institutes of Health
Regulation of bacterial gene expression by transcriptional attenuation
Our research program studies the regulation of metabolism as exemplified by the control of biosynthetic enzymes during bacterial growth and differentiation. A second research theme is the study of the active sites, mechanism of catalysis and of allosteric regulation of enzymes of nucleotide biosynthesis. A current focal point is the regulation of transcription of the ten-cistron pyrimidine biosynthetic (pyr) operon in Bacillus subtilis, which we have shown to be governed by the protein, called PyrR, encoded by the first gene of the operon. This protein, which also catalyzes uracil phosphoribosyltransferase activity, promotes transcriptional termination at three attenuation sites in the pyr operon. PyrR acts by binding in a uridine nucleotide dependent manner to specific sites on pyr mRNA and altering its conformation, so that a transcription terminator is formed. The PyrR protein has been purified to homogeneity and its 3D structure has been determined. Our current objectives are to characterize the PyrR protein, the RNA to which it binds, and the PyrR-RNA interaction at high resolution. The regulatory activities of PyrR are being examined by physical, biochemical and genetic methods. We are examining regulation of pyr genes by PyrR in other bacteria, including clinically important pathogens.
Our laboratory also studies the regulation by transcriptional antitermination of the B. subtilis pyrG gene, which encodes CTP synthase. This gene is regulated independently of the pyr operon by a highly novel mechanism, which involves reiterative transcription or "transcriptional slippage" and no regulatory protein. We are extending our understanding of this mechanism by genetic and biochemical approaches.
Prof. Switzer no longer accepts research associates or students because his laboratory was closed in 2008.
Jørgensen. C. M., Fields, C. J., Chander, P., Watt, D., Burgner, J. W., II, Smith, J. L., and Switzer, R. L. (2008) "pyr RNA Binding to the Bacillus caldolyticus PyrR Attenuation Protein: Characterization and Regulation by Uridine and Guanosine Nucleotides." FEBS Journal, 275, 655-670.
Turnbough, C. L., Jr., and Switzer, R. L. (2008) "Regulation of Pyrimidine Biosynthetic Gene Expression in Bacteria: Repression without Repressors, "Microbiol. Molec. Biol. Rev. 72, 266-300
Switzer, R. L. (2009) "Discoveries in Bacterial Nucleotide Metabolism," J. Biol. Chem. 284, 6585-6594
Elsholz, A.K.W., Jørgensen, C.M., and Switzer, R.L. 2007. The number of G residues in the Bacillus subtilis pyrG initially transcribed region governs reiterative transcription-mediated regulation. J. Bacteriol., 189:2176–80. [Abstract]
Jensen-McAllister, I.E., Meng, Q., and Switzer, R.L. 2007. Regulation of pyrG expression in Bacillus subtilis: CTP-regulated antitermination and reiterative transcription with pyrG templates in vitro. Molec. Microbiol., 63:1440–52. [Abstract]
Fields, C.J. and Switzer, R.L. 2007. Regulation of pyr gene expression in Mycobacterium smegmatis by pyrR-dependent translational repression. J. Bacteriol., 189: 6236-6245. [Abstract]
Gerth, U., Kock, H., Küsters, I., Michalik, S., Switzer, R.L., and Hecker, M. 2008. Clp dependent proteolysis down-regulates central metabolic pathways in glucose-starved Bacillus subtilis. J. Bacteriol., 190, 321-331.
Chander, P., Halbig, K.M., Miller, J.K., Fields, C.J., Bonner, H.K.S., Grabner, G.K., Switzer, R.L., and Smith, J.L. 2005. Structure of the nucleotide complex of pyrR, the pyr attenuation protein from Bacillus caldolyticus suggests dual regulation by pyrimidine and purine nucleotides. J. Bacteriol., 187:1773–82. [Abstract]
Meng, Q., Turnbough, C.L., Jr., and Switzer, R.L. 2004. Attenuation control of pyrG expression in Bacillus subtilis is mediated by CTP-sensitive reiterative transcription. Proc. Natl. Acad. Sci. U.S.A., 101:10943–8. [Abstract]
Grabner, G.K. and Switzer, R.L. 2003. Kinetic studies of the uracil phosphoribosyltransferase reaction catalyzed by the Bacillus subtilis pyrimidine attenuation regulatory protein pyrR. J. Biol. Chem., 278:6921–7. [Abstract]
Zhang, H. and Switzer, R.L. 2003. Transcriptional pausing in the Bacillus subtilis pyr operon: a role in regulation of expression? J. Bacteriol., 185:4764–71. [Abstract]
Meng, Q. and Switzer, R.L. 2002. "The cis-acting sequences of Bacillus subtilis pyrG mRNA essential for regulation by antitermination. J. Bacteriol., 184:6734–8. [Abstract]
Savacool, H.K. and Switzer, R.L. 2002. Characterization of the interaction of Bacillus subtilis pyrR with pyr mRNA by site-directed mutagenesis of the protein. J. Bacteriol., 184:2521–8. [Abstract]