College of Computer, Mathematical, and Natural Sciences

Wade C. Winkler

Winkler

Associate Professor

Contact

Office Phone: 301.405.7780
Lab Phone: 301.405.9937
Lab: 3112 Bioscience Research Building
Office Address: 3115 Bioscience Research Building

Graduate Program Affiliations

  • BISI - BISI-Molecular & Cellular Biology (MOCB)

Research Interests


The regulation of transcription initiation by DNA-binding transcription factors has long been presumed to be the primary mode of genetic regulation in bacteria. Indeed, most bacteria encode for ~100-300 transcription factors. However, initiation is only the first step; many downstream events are also critically important in establishing mRNA and protein levels. In fact, it has become increasingly obvious in the past decade that post-initiation regulatory mechanisms are much more common that previously realized. These post-initiation regulatory strategies can exert their influence over several processes, including transcription elongation, translation efficiency, and mRNA stability. The specific goal of the Winkler laboratory is to discover the molecular mechanisms, overall usage and synthetic applications of post-initiation regulatory strategies in bacteria. Our long-term goal in elucidating these regulatory circuits is to uncover fundamentally important regulatory features in pathogenic microbes and to uncover new potential targets for development of antimicrobial compounds. 

Education

Ph.D. The Ohio State University, 2002
Postdoctoral Training, Yale University 2004 

Recent Publications

DebRoy S^, Gebbie M^, Ramesh A, Goodson JR, Cruz MR, van Hoof A, Winkler WC*, Garsin DA*. 2014. A riboswitch-containing sRNA controls gene expression by sequestration of a response regulator. Science. In Press (^ = equal contribution; * = corresponding authors).

Shin JH, Wakeman CA, Goodson JR, Rodionov DA, Freedman BG, Senger RS, Winkler WC. 2014. Transport of magnesium by a bacterial Nramp-related gene. PLoS Genetics 10:e1004429. (http://www.ncbi.nlm.nih.gov/pubmed/24968120) 

Wakeman CA, Goodson JR, Zacharia VM, Winkler WC. 2014. An Assessment of the requirements for magnesium tranpsorters in Bacillus subtilis. J Bacteriol 196:1206-14. (http://www.ncbi.nlm.nih.gov/pubmed/24415722)

Dambach M, Irnov I, Winkler WC. 2013. Association of RNAs with Bacillus subtilis Hfq. PLoS ONE 8:e55156. (http://www.ncbi.nlm.nih.gov/pubmed/23457461)

Ramesh A, DebRoy S, Goodson JR, Fox KA, FazH, Garsin DA, Winkler WC. 2012. The mechanism for RNA recognition by ANTAR regulators of gene expression. PLoS Genetics 8:e1002666. (http://www.ncbi.nlm.nih.gov/pubmed/22685413)   

Ferré-D’Amare AR, Winkler WC. 2011. The roles of metal ions in regulation by riboswitches. Met Ions Life Sci 9:141-73. (http://www.ncbi.nlm.nih.gov/pubmed/22010271)

Ramesh A, Wakeman CA, Winkler WC. 2011. Insights into metalloregulation by M-box riboswitch RNAs via structural analysis of manganese-bound complexes. J Mol Biol 407:556-70. (http://www.ncbi.nlm.nih.gov/pubmed/21315082)

Irnov I, Sharma CM, Vogel, J, Winkler WC. 2010. Identification of regulatory RNAs in Bacillus subtilis. Nucleic Acids Research 38:6637-51. (http://www.ncbi.nlm.nih.gov/pubmed/20525796)

Irnov I, Winkler WC. 2010. A regulatory RNA required for antitermination of biofilm and capsular polysaccharide operons in Bacillales. Mol Microbiol 75:559-75. (http://www.ncbi.nlm.nih.gov/pubmed/20374491)

Wakeman CA, Ramesh A, Winkler WC. 2009. Multiple metal binding cores are required for metalloregulation by M box riboswitch RNAs. J Mol Biol 392:723-35. (http://www.ncbi.nlm.nih.gov/pubmed/19619558)

Ramesh A, Winkler WC. 2010. Magnesium-sensing riboswitches in bacteria. RNA Biol 7:Epub ahead of print. (http://www.ncbi.nlm.nih.gov/pubmed/20023416)

Fox KA*, Ramesh A*, Stearns JE, Bourgogne A, Reyes A, Winkler WC*, Garsin DA*. 2008. Multiple posttranscriptional regulatory mechanisms partner to control ethanolamine utilization in Enterococcus faecalis. Proc Natl Acad Sci 106:4435-4440. (*equal contribution). (http://www.ncbi.nlm.nih.gov/pubmed/19246383) 

Wakeman CA, Winkler WC. 2009. Analysis of the RNA backbone: Structural analysis of riboswitches by in-line probing and selective 2'-hydroxyl acylation and primer extension (SHAPE). Methods Mol Biol 540:173-191.(http://www.ncbi.nlm.nih.gov/pubmed/19381560)

Brautigam CA, Wakeman CA, Winkler WC. 2009. Methods for analysis of ligand-induced RNA conformational changes. Methods Mol Biol 540:77-95. (http://www.ncbi.nlm.nih.gov/pubmed/19381554)

Wakeman CA, Winkler WC. 2009. Structural probing techniques for natural aptamers. Methods Mol Biol 535:115-133. (http://www.ncbi.nlm.nih.gov/pubmed/19377977)

Dambach M, Winkler WC. 2009. Expanding roles for metabolite-sensing RNAs. Curr Opin Microbiol 12:161-169. (http://www.ncbi.nlm.nih.gov/pubmed/19250859)

Attia AS, Sedillo JL, Wang W, Liu W, Brautigam CA, Winkler WC, Hansen EJ. 2008. Moraxella catarrhalis expresses an unusual Hfq protein. Infect Immun 76:2520-2530

Collins JA, Irnov I, Baker SC, Winkler WC. 2007. Mechanism of mRNA destabilization by the glmS ribozyme. Genes & Dev 21:3356-3368. (http://www.ncbi.nlm.nih.gov/pubmed/18079181)

Dann CE*, Wakeman CA*, Sieling CL, Baker SC, Irnov I, Winkler WC. 2007. Structure and mechanism of a metal-sensing regulatory RNA. Cell 130:878-892. (*equal contribution). (http://www.ncbi.nlm.nih.gov/pubmed/17803910)

Wakeman CA, Winkler WC, Dann CE. 2007. Structural features of metabolite-sensing riboswitches. Trends Biochem Sci 32:415-424. (http://www.ncbi.nlm.nih.gov/pubmed/17764952)

Roth A, Winkler WC, Regulski EE, Lee BW, Lim J, Jona I, Barrick JE, Ritwick A, Kim JN, Welz R, Iwata-Reuyl D, Breaker RR. 2007. A riboswitch selective for the queuosine precursor preQ(1) contains an unusually small aptamer. Nat Struct Mol Biol 14:308-317

Irnov, Kertsburg A, Winkler WC. 2006. Genetic control by cis-acting regulatory RNAs in Bacillus subtilis: General principles and prospects for discovery. Cold Spring Harb Quant Biol 71:239-249.(http://www.ncbi.nlm.nih.gov/pubmed/17381303)

Winkler WC, Dann CE. 2006. RNA allostery glimpsed. Nat Struct Mol Biol 13:569-571

Winkler WC. 2005. Riboswitches and the role of noncoding RNAs in bacterial metabolic control. Curr Opin Chem Biol 9:594-602

Winkler WC, Breaker RR. 2005. Regulation of bacterial gene expression by riboswitches. Ann Rev Microbiol 59:487-517

Wickiser JK, Winkler WC, Breaker RR, Crothers D. 2005. The speed of RNA transcription and metabolite binding kinetics operate an FMN riboswitch. Molecular Cell 18:49-60

Lim J, Winkler WC, Nakamura S, Scott V, Breaker RR. 2005. Molecular-recognition characteristics of SAM-binding riboswitches. Agnew Chem Int Ed Engl 34:964-968

Winkler WC. 2005. Metabolic monitoring by bacterial mRNAs. Archives in Microbiol 183:151-159

Barrick JE, Corbino KA, Winkler WC, Nahvi A, Mandal M, Collins J, Lee M, Roth A, Sudarsan N, Jona I, Wickiser JK, Breaker RR. 2004. RNA motifs suggest an expanded scope for riboswitches in bacterial genetic control. Proc Natl Acad Sci 101:6421-6426

Winkler WC*, Nahvi A*, Roth A*, Collins JA*, Breaker RR. 2004. Control of bacterial gene expression by a natural metabolite-responsive ribozyme. Nature. 428:281-286

Winkler WC, Nahvi A, Sudarsan N, Barrick JE, Breaker RR. 2003. An mRNA structure that controls gene expression by binding S-adenosylmethionine. Nat Struct Biol 10:701-707

Mandal M, Boese B, Barrick JE, Winkler WC, Breaker RR. 2003. Metabolite-sensing riboswitches control fundamental biochemical pathways, in bacteria. Cell 113:577-586

Winkler WC, Breaker RR. 2003. Genetic control by metabolite-binding riboswitches. ChemBioChem 4:1024-1032

Winkler WC, Cohen-Chalamish S, Breaker RR. 2002. An mRNA structure that controls gene expression by binding FMN. Proc Natl Acad Sci 99:15908-15913

Winkler W, Nahvi A, Breaker RR. 2002. Thiamine derivatives bind messenger RNAs directly to regulate bacterial gene expression. Nature 419:952-956

Grundy FJ, Winkler WC, Henkin TM. 2002. tRNA-mediated transcription antitermination in vitro: Codon-anticodon pairing independent of the ribosome. Proc Natl Acad Sci 99:11121-11126

Winkler WC, Grundy FJ, Murphy BA, Henkin TM. 2001. The GA motif: An RNA element common to bacterial antitermination systems, rRNA, and eukaryotic RNAs. RNA 7:1165-1172

Curnow AW, Hong K, Yuan R, Kim S, Martins O, Winkler W, Henkin TM, Soll D. 1997. Glu-tRNAGln amidotransferase: A novel heterotrimeric enzyme required for correct decoding of glutamine codons during translation. Proc Natl Acad Sci 94:11819-11826

Winkler WC, Gonzalez G, Wittenberg JB, Hille R, Dakappagari N, Jacob A, Gonzalez LA, Gilles-Gonzalez MA. 1996. Nonsteric factors dominate binding of nitric oxide, azide, imidazole, cyanide, and fluoride to the Rhizobial heme-based oxygen sensor FixL. Chem and Biol 3:841-850

Education

Ph.D. The Ohio State University, 2002
Postdoctoral Training, Yale University 2004