We have identified multiple new "drug targets" within the structure of bacterial RNA polymerase, the enzyme that mediates bacterial gene expression. Each of these new targets can serve as a binding site for compounds that inhibit bacterial gene expression and thereby kill bacteria. For each of these new targets, we have identified at least one "lead compound" that binds to the new target and have characterized the activity of the lead compound. Several of the lead compounds exhibit exceptionally high promise, exhibiting potent activity against a broad spectrum of priority public-health bacterial pathogens and priority biodefense bacterial pathogens (including the pathogens responsible for tuberculosis, staph infections, strep infections, anthrax, and plague), and exhibiting no cross resistance with current antibiotics.
Undergraduate projects will focus on (1) identification and characterization of new targets, (2) identification and characterization of new lead compounds, and/or (3) synthesis and characterization of optimized lead compounds.
GPA >=3.7 required.
Major in chemistry or molecular biology required.
Prior research experience in synthetic organic chemistry or molecular biology desirable.
Applications through Aresty Research Program preferred.
Publications with Undergraduate Co-authors
Niu, W., Kim, Y., Tau, G., Heyduk, and Ebright, R. (1996) Transcription activation at Class II CAP dependent promoters: two interactions between CAP and RNA polymerase. Cell 87, 1123 1134.
Parkinson, G., Wilson, C., Gunasekera, A., Ebright, Y., Ebright, R. and Berman, H. (1996) Structure of the CAP-DNA complex at 2.5 Å resolution: a complete picture of the protein-DNA interface. J. Mol. Biol. 260, 395-408.
Bayro, M., Mukhopadhyay, J., Swapna, G.V.T., Huang, J., Ma, L.-C., Sineva, E., Dawson, P., Montelione, G., and Ebright, R. (2003) Structure of antibacterial peptide microcin J25: a 21-residue lariat protoknot. J. Amer. Chem. Soc. 125, 12382 12383.