A.B., 1981, Ph.D. 1987, Harvard Harvard Junior Fellow 1984-1987 Awards & Honors Searle Scholar Award, 1989 Johnson & Johnson Discovery Research Fellow, 1990 American Society for Biochemistry and Molecular Biology/Schering-Plough Research Achievement Award, 1995 Walter J. Johnson Prize, 1995 American Academy of Microbiology Fellow,1996 Howard Hughes Medical Institute Investigator, 1997 Rutgers University Board of Trustees Research Excellence Award, 1998 American Association for the Advancement of Science Fellow, 2004 Infectious Diseases Society of America Fellow, 2011 Theobald Smith Society Waksman Award, 2012

Biophysical Chemistry

Protein-DNA interaction, protein engineering, regulation of gene expression Transcription--the synthesis of an RNA copy of genetic information in DNA--is the first step in gene expression and is the step at which most regulation of gene expression occurs. Richard H. Ebright's laboratory seeks to understand structures, mechanisms, and regulation of bacterial transcription complexes and to identify, characterize, and develop small-molecule inhibitors of bacterial transcription for application as antituberculosis agents and broad-spectrum antibacterial agents.

Feklistov, A., Mekler, V., Jiang, Q., Westblade, L., Irschik, H., Jansen, R., Mustaev, A., Darst, S., and Ebright, R.H. (2008) Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center. Proc. Natl. Acad. Sci. USA 105, 14820-14825. Mukhopadhyay, J., Das, K., Ismail, S., Koppstein, D., Jang, M., Hudson, B., Sarafianos, S., Tuske, S., Patel, J., Jansen, R., Irschik, H., Arnold, E., and Ebright, R. (2008) The RNA polymerase "switch region" is a target of inhibitors Cell 135, 295-307. Pavlova, O., Mukhopadhyay, J., Sineva, E., Ebright, R., and Severinov, K. (2008) Systematic structure-activity analysis of microcin J25 (MccJ25). J. Biol. Chem. 283, 25589-25595. Kim, Y., Ebright, Y., Goodman, A., Reinberg, D., and Ebright, R. (2008) Non-radioactive, ultrasensitive site-specific protein-protein photocrosslinking: interactions of a-helix 2 of TATA-binding protein with general transcription factor TFIIA and with transcriptional repressor NC2. Nucl. Acids Res. 36, 6143-6154. Naryshkin, N., Druzhinin S., Revyakin, A., Kim, Y., Mekler, V., and Ebright, R. (2009) Static and kinetic site-specific protein-DNA photocrosslinking: analysis of bacterial transcription initiation complexes. Meths. Mol. Biol. 543, 403-437. Popovych, N., Tzeng, S.-R., Tonelli, M., Ebright¬, R., and Kalodimos, C. (2009) Structural basis of cAMP-mediated allosteric control of the catabolite activator protein, Proc. Natl. Acad. Sci. USA 106, 6927-6932. Goldman, S., Ebright, R., and Nickels, B. (2009) Direct detection of abortive RNA transcripts in vivo. Science 324, 927-928. Hudson, B., Quispe, J., Lara, S., Kim, Y., Berman, H., Arnold, E., Ebright, R., and Lawson, C. (2009) Three-dimensional structure of an intact activator-dependent transcription initiation complex. Proc. Natl. Acad. Sci. USA 106, 19830-19835. Ho, M., Hudson, B., Das, K., Arnold, E., and Ebright, R. (2009) Structures of RNA polymerase-antibiotic complexes. Curr. Opin. Structl. Biol. 19, 715-723. Chakraborty, A., Wang, D., Ebright, Y., and Ebright, R. (2010) Azide-specific labelling of biomolecules by Staudinger-Bertozzi ligation: phosphine derivatives of fluorescent probes suitable for single-molecule fluorescence spectroscopy. Meths. Enzymol. 472, 19-30. Grohmann, D., Nagy, J., Chakraborty, A., Klose, D., Fielden, D., Ebright, R., Michaelis, J., and Werner, F. (2011) The initiation factor TFE and the elongation factor Spt4/5 compete for binding to the RNAP clamp during transcription initiation and elongation. Mol. Cell 43, 263-274. Xiao, Y., Wei, X., Ebright, R., and Wall, D. (2011) Antibiotic production by myxobacteria plays a role in predation. J. Bacteriol. 193, 4626-4633. Kuznedelov, K., Semenova, E., Knappe, T., Mukahmedjarov, D., Srivastava, A., Chatterjee, S., Ebright, R., Marahiel, M., and Severinov, K. (2011) The antibacterial threaded-lasso peptide capistruin inhibits bacterial RNA polymerase. J. Mol. Biol. 412, 842-848. Srivastava, A., Talaue, M., Liu, S., Degen, D., Ebright, R.Y., Sineva, E., Chakraborty, A., Druzhinin, S., Chatterjee, S., Mukhopadhyay, J., Ebright, Y., Zozula, A., Shen, J., Sengupta, S., Niedfeldt, R., Xin, C., Kaneko, T., Irschik, H., Jansen, R., Donadio, S., Connell, N., and Ebright, R. (2011) New target for inhibition of bacterial RNA polymerase: "switch region." Curr. Opin. Microbiol. 14, 532-543. Ebright, R. Switch region: target and method for inhibition of bacterial RNA polymerase. US Patent #8,114,583. Ebright, R. (2012) Target and method for inhibition of bacterial RNA polymerase. US Patent #8,198,021. Ebright, R. (2012) RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US Patent #8,206,898. Chakraborty, A., Wang, D., Ebright, Y., Korlann, Y., Kortkhonjia, E., Kim, T., Chowdhury, S., Wigneshweraraj, S., Irschik, H., Jansen, R., Nixon, B.T., Knight, J., Weiss, S., and Ebright, R. (2012) Opening and closing of the bacterial RNA polymerase clamp. Science 337, 591-595. Srivastava, A., Degen, D., Ebright, Y., and Ebright, R. (2012) Frequency, spectrum, and nonzero fitness costs of resistance to myxopyronin in Staphylococcus aureus. Antimicrob. Agents Chemother. 56, 6250-6255. Zhang, Y., Feng, Y., Chatterjee, S., Tuske, S., Ho, M., Arnold, E., and Ebright, R. (2012) Structural basis of transcription initiation. Science 338, 1076-1080. Seul, M. and Ebright, R. (2013) Color-encoding and in-situ interrogation of matrix-coupled chemical compounds. Canadian Patent CA2291853. Ebright, R., Mukhopadhyay, J., Severinov, K., and Semenova, E. (2013) Non-MccJ25-related lariat-peptide inhibitors of bacterial RNA polymerase. US Patent US8354246. Ebright, R. and Wang, D. (2013) Bipartite inhibitors of bacterial RNA polymerase. US Patent 8372839. Robb, N., Cordes, T., Hwang, L., Gryte, K., Duchi, D., Craggs, T., Santoso, Y., Weiss, S., Ebright, R., and Kapanidis, A. (2013) The transcription bubble of the RNA polymerase-promoter open complex exhibits conformational heterogeneity and millisecond-scale dynamics: implications for transcription start-site selection. J. Mol. Biol. 425, 875–885. Ebright, R. and Severinov, K., (2013) Nucleic acid sequences for biosynthesis of non-MccJ25-related lariat peptides. US Patent 8461314. Ebright, R. (2013) Target and method for inhibition of bacterial RNA polymerase. US Patent 8575306. Vorobiev, S., Kramer, Y., Vahedian-Movahed, H., Seetharaman, J., Sua, M., Huang., J., Xiao, R., Kornhaber, G., Montelione, G., Tong, L., Ebright, R., and Nickels, B. (2014) Structure of the DNA binding and RNA polymerase binding region of transcription antitermination factor Q. Structure 22, 488 495. Ebright, R. (2014) RNA exit channel: target and method for inhibition of bacterial RNA polymerase. US Patent 8697354. Zhang, Y., Degen, D., Ho, M., Sineva, E., Ebright, K., Ebright, Y., Mekler, V., Vahedian-Movahed, H., Feng, Y., Yin, R., Tuske, S., Irschik, H., Jansen, R., Maffioli, S., Donadio, S., Arnold, E., and Ebright, R. (2014) GE23077 binds to the RNA polymerase "i" and "i+1" sites and prevents the binding of initiating nucleotides. eLife, e02450. Degen, D., Feng, Y., Zhang, Y., Ebright, K., Ebright, Y., Gigliotti, M., Vahedian-Movahed, H., Mandal, S., Talaue, M., Connell, N., Arnold, E., Fenical, W., and Ebright, R. (2014) Transcription inhibition by the depsipeptide antibiotic salinamide A. eLife, e02451.