Sarah W. Woodson, Ph.D. Professor Department of Biophysics Professor Department of Biology CMDB Graduate Program Faculty B.S. Kalamazoo College Ph.D. Yale University

[Research Interests] [Representative Publications]

RESEARCH INTERESTS

RNA molecules play a role in nearly every aspect of gene expression, including transcription, splicing, protein synthesis, and translational control. In order to perform these diverse functions, RNAs must fold into intricate three-dimensional structures and complex with specific proteins. How the components of large RNA-protein complexes assemble remains a challenging problem with applications to human genetics, cancer and virology.

We are using biochemical and physical methods to understand the folding mechanism of large RNAs, the assembly of the ribosome, and interactions between small anti-sense regulatory RNAs with their mRNA targets. Important questions that remain to be addressed are how intracellular conditions influence the folding pattern of new transcripts, how proteins facilitate the assembly of very large RNA complexes such as the ribosome, and how incorrectly folded RNAs are recognized and targeted for degradation.

In collaboration with Michael Brenowitz and Mark Chance at Albert Einstein Center for Synchrotron Biosciences, we have developed a synchrotron "X-ray footprinting" method to probe the tertiary structure of RNA with millisecond time resolution, yielding “snapshots” of the RNA structure as it forms. This method is being used to probe the kinetic folding pathway of ribozymes and assembly of the 30S ribosome.

Stopped-flow fluorescence spectroscopy, small angle X-ray scattering, and neutron diffraction provide a global picture of RNA dynamics. Biochemical experiments and fluorescence are also providing insights into how the RNA chaperone Hfq faciliates the annealing and exchange of RNA double helices. Finally, simple expression assays in bacteria or yeast are used to probe the function of the RNA in cells and to screen for proteins that “chaperone” RNA folding.

REPRESENTATIVE PUBLICATIONS

Chauhan, S. and Woodson, S. A. 2008. Tertiary interactions determine the accuracy of RNA folding.  J. Amer. Chem. Soc.,130, 1296-1303.

Adilakshmi T., Lease, R. A., Heilman-Miller S. L. and Woodson, S. A. 2007. Communication between RNA folding domains revealed by folding of circularly permuted ribozymes.  J. Mol. Biol. 373, 197-210.

Jackson, S. A., Koduvayur, S. and Woodson, S. A. 2006. Self-splicing of a group I intron reveals partitioning of native and misfolded RNA populations in yeast.  RNA 12, 2149-2159.

Adilakshmi T., Lease, R. A. and Woodson, S. A. 2006. Hydroxyl radical footprinting in vivo: mapping macromolecular structures with synchrotron radiation.  Nucl. Acids Res. 34, e64.

Hopkins, J. F. and Woodson, S. A. 2005. Molecular beacons as probes of RNA unfolding under native conditions.  Nucl. Acids. Res. 33, 5763-5770.

Woodson, S. A. 2005. Metal ions and RNA folding:  a highly charged topic with a dynamic future.  Curr. Opin. Chem. Biol. 9, 104-109.

Lease, R. A. and Woodson, S. A. 2004. Cycling of the Sm-like protein Hfq on the DsrA small regulatory RNA.  J. Mol. Biol. 344, 1211-1123 (cover).

Lab Members

 
Postdoctoral Fellows:
Joon Hoh Roh
 
Graduate Students:
Reza Behrouzi
Seema Chauhan
Sarah Clatterbuck Soper
Toby Soper