UM Biophysics Faculty | Nils G Walter

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Nils G Walter

Folding and Function of Catalytic RNA; Biophysical Chemistry of Nucleic Acids

Nils at his birthday party

Dow Corning Assistant Professor of Chemistry

Ph.D., Max-Planck Institute, Technical University of Darmstadt

Dept: Chemistry

Office Address: 4821 Chemistry Building

Phone: (734) 615-2060

Email: nwalter@umich.edu

Group Home Page

Our highly interdisciplinary group studies the folding of catalytic non-coding RNAs (ribozymes) with fluorescence techniques of sensitivities up to the single-molecule level. We are fascinated by how RNA is able to catalyze and facilitate complex chemical reactions, dismantling the dogma that protein enzymes are the sole biological carriers of catalytic activity. Ribozyme structures are extremely dynamic over time scales of microseconds to hours. The major goal of our group is to understand these dynamics by the combined use of state-of-the-art biophysical and biochemical approaches, spanning both experiment and theory (advanced molecular dynamics simulations). We aim to identify and optimize ribozymes for gene therapy applications within cells and explore their use as single-molecule biosensors.

The systems we study range from pathogenic RNAs, such as that of the human hepatitis delta virus, to large cellular machines that process genetic information, such as the ribosome and the RNA-induced silencing complex (RISC). Steady-state and time-resolved fluorescence measurements as well as molecular dynamics (MD) simulations allow us to ask questions such as: How does an RNA fold into a functional structure? Are there conformationally distinct RNA molecules present? Do multiple folding pathways exist that lead to identical catalytic structures? What influence do cofactors and sequence modifications have? Particularly our single-molecule fluorescence microscopy enables us to solve these exciting problems by directly monitoring individual RNA molecules as they fold and unfold.

For more information, please see our group webpage listed above.

Awards:
Camille Dreyfus Teacher-Scholar Award 2004
Dow Corning Assistant Professorship 2003 of the University of Michigan
Otto-Hahn medal 1995 for Outstanding Researchers of the Max-Planck Society
Feodor-Lynen Postdoctoral Research Fellowship from the Alexander von Humboldt Foundation
Kekule Ph.D.Scholarship from the Stiftung Stipendienfonds des Verbandes der Chemischen Industrie
Anton Keller Prize for best Chemistry Diploma of the Year at the Technical University of Darmstadt
Study Scholarship from the Studienstiftung des Deutschen Volkes

Representative Publications

NG Walter, DA Harris, MJB Pereira, D. Rueda. In the fluorescent spotlight: global and local conformational changes of small catalytic RNAs. Biopolymers 2002, 61, 224.

X Zhuang, H Kim, MJB Pereira, HP Babcock, NG Walter, S Chu. Coupling of structural dynamics and function in single ribozyme molecules. Science 2002, 296, 1473.

NG Walter, D Engelke. Ribozymes: Catalytic RNAs that cut things, make things, and do odd and useful jobs. The Biologist 2002, 49, 199.

PT Sekella, D Rueda, NG Walter. A biosensor for theophylline based on fluorescence detection of ligand-induced hammerhead ribozyme cleavage. RNA 2002, 8, 1242.

G Bokinsky, D Rueda, VK Misra, A Gordus, MM Rhodes, HP abcock, NG Walter, X Zhuang. Single-molecule transition-state analysis of RNA folding. Proc. Natl. Acad. Sci. USA 2003, 100, 9302.

K Wick, SE McDowell, NG Walter. Diffusely bound Mg²⁺ Ions Orient Stems I and II of the Hammerhead Ribozyme to Increase the Probability for Formation of the Catalytic Core. Biochemistry 2003, 42, 9924.

RA Tinsley, DA Harris, and NG Walter. Magnesium dependence of the amplified conformational switch in the trans-acting hepatitis delta virus ribozyme. Biochemistry 2004, 43, 8935-8945.

D Rueda, G Bokinsky, MM Rhodes, MJ Rust, X Zhuang, and NG Walter. Single-molecule enzymology of RNA: Essential functional groups impact catalysis from a distance. Proc. Natl. Acad. Sci. USA 2004, 101, 10066-10071.

MV Krasovska, J Sefcikova, N Špacková, J Šponer, and NG Walter. Structural dynamics of precursor and product of the RNA enzyme from the hepatitis delta virus as revealed by molecular dynamics simulations. J. Mol. Biol. 2005, 351, 731-748.

D Rueda, J Hsieh, JJ Day-Storms, CA Fierke, and NG Walter. The 5' leader of precursor tRNAAsp bound to the Bacillus subtilis RNase P holoenzyme has an extended conformation. Biochemistry 2005, 44, 16130-16139.

D. Rueda and NG Walter. Single molecule fluorescence control for nanotechnology. J. Nanosci. Nanotechnol. 2005, 5, 1990-2000.

NG Walter. Michaelis-Menten is dead, long live Michaelis-Menten! Nature Chem. Biol. 2006, 2, 66-67.

MN Lambert, E Vöcker, S Blumberg, S Redemann, A Gajraj, JC Meiners and NG Walter. Mg²⁺-Induced compaction of single RNA molecules monitored by tethered particle microscopy. Biophys. J. 2006, 90, 3672-3685.

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Biophysics Research Division University of Michigan 4028 Chemistry Building 930 North University Avenue Ann Arbor, MI 48109-1055 UMsitemaker	Phone: (734) 763-6722 Fax: (734) 764-3323 E-mail: biophysics@umich.edu Last Updated: 5/4/2006 © Copyright 2006 University of Michigan