Assistant Professor of Biochemistry, Biophysics and Structural Biology*
*and of Chemistry
The long-term goals of the Hammond group are to investigate the molecular basis of function for naturally-occurring regulatory RNAs and to learn how to adapt these RNAs for new applications inside cells, including molecular sensing and gene control. We employ biochemistry, genetics, organic synthesis, and bioinformatics to study small molecule-RNA and protein-RNA interactions that are involved in gene regulation in bacteria and plants. Our research aims to provide new insights into the regulation of gene expression in these organisms, and furthermore has applications toward engineering bacteria and plants for biofuel production and other biotechnology projects.
Beyond the messenger
Riboswitches are RNA structures found primarily within the untranslated region of mRNAs in bacteria that form precise receptors for small molecules and regulate gene expression in response to ligand binding. Each riboswitch is naturally evolved to function robustly inside cells. To do so, it must fold properly, bind its ligand specifically in the presence of other metabolites, and affect gene expression. Recent studies have hinted at the potential of riboswitches as robust platforms upon which to evolve new in vivo functions, but this approach remains under-developed. We use chemical biology approaches to study and manipulate riboswitches in projects that relate to molecular sensing inside cells and other cellular applications.
Most genetic engineering efforts to improve plant characteristics involve constant expression of gene or knock-out of genes. However, these strategies may lead to detrimental effects on plant growth and development in addition to the desired beneficial effect. We seek to develop an RNA-based technology to control the expression of introduced genes that can be used in a variety of biofuel crops and can be readily combined with other regulatory mechanisms that function at the DNA level.
Projects in the lab pursue the following:
- Reengineering functional RNAs
- Elucidating mechanisms of RNA-based gene regulation
- Targeting RNAs with small molecules
Hickey, S. F., Sridhar, M., Westermann, A. J., Qin, Q., Vijayendra, P. Liou, G., Hammond, M. C. "Transgene regulation in plants by alternative splicing of a suicide exon" Nucleic Acids Res (2012), 40, 4701-10.
Hammond, M. C. "A tale of two riboswitches" Nat Chem Biol (2011), 7, 342-3.
Meyer, M. M., Hammond, M. C., Salinas, Y., Roth, A., Sudarsan, N., Breaker, R. R. "Challenges of ligand identification for riboswitch candidates" RNA Biol (2011), 8, 5-10.
Block, K. F., Hammond, M. C., Breaker, R.R. “Evidence for widespread gene control function by the ydaO riboswitch candidate” J Bacteriol (2010), 192, 3983-9.
Hammond, M. C., Wachter, A., Breaker, R. R. “A plant 5S rRNA mimic regulates alternative splicing of transcription factor IIIA pre-mRNAs” Nat Struct and Mol Biol (2009), 16, 541-9.
Weinberg, Z., Regulski, E. E., Hammond, M. C., Barrick, J. E., Yao, Z., Ruzzo, W. L., Breaker, R. R. “The aptamer core of SAM-IV riboswitches mimics the ligand-binding site of SAM-I riboswitches” RNA (2008), 14, 822-8.
Hammond, M. C., Bartlett, P. A. “Synthesis of amino acid-derived cyclic acyl amidines for use in beta-strand peptidomimetics” J Org Chem (2007), 72, 3104-07.
Hammond, M. C., Harris, B. Z.; Lim, W. A., Bartlett, P. A. “Beta-strand peptidomimetics as potent PDZ ligands” Chem Biol (2006), 13, 1247-51.
Sudarsan, N.*, Hammond, M. C.*, Block, K. F., Welz, R., Barrick, J. E., Roth, A., Breaker, R. R. “Tandem riboswitch architectures exhibit complex gene control functions” Science (2006), 314, 300-304.
Last Updated 2012-08-17