Faculty

Newly discovered small non-coding (nc)RNAs, some of them catalytically capable ribozymes, play a universal role in the processing and regulation of genetic information. Our group's goal is to understand the structure-function relationships in these ncRNAs and ribozymes and then utilize them for biomedical, bioanalytical and nanotechnological applications. The enzymes we study range from small RNA catalysts, such as the hammerhead, hairpin and hepatitis delta virus ribozymes with potential use in human gene therapy and relevance to human disease, to large RNA-protein complexes, such as the ribosome, the cellular protein synthesis machinery. In particular, we employ flourescence techniques to study in real-time the enzymology of these ncRNAs, in bulk solution, in live cells and at the single-molecule level. Applications include the identification and optimization of ribozymes for gene therapy and as novel biosensors, as well as the characterization of antiviral and antibiotic drugs that target pathogenic RNA function.

Our research by its very nature is highly interdisciplinary, engaging students with a diverse background and providing a broad education. The molecules we study are extremely dynamic over time scales of microseconds to hours. To understand these dynamics we combine state-of-the-art chemical, molecular biological and biophysical approaches. An outline of several exciting current projects follows:

Developing a model system for understanding gene silencing by directly observing, using flourescence techniques, the degradation of small interfering (si)RNAs and micro (mi)RNAs in cell extracts and live cells.
Utilizing single molecule flourescence imaging techniques to follow movement of the ribosome on a secondary structured mRNA.
Utilizing single molecule flourescence imaging techniques in nanotechnology to follow autonomously moving engineered "molecular spiders."

Generating new biosensors for high-throughput screening of the broncho-dilator drug theophylline, by directly monitoring the cleavage activity of a theophylline controlled hammerhead ribozyme by FRET.

Awards

Visiting Scholar, Harvard University (Sunney Xie group), 2006
Alumnus of the Year Award, Sherbrooke RiboClub, 2006
JILA Distinguished Visitor Fellowship, 2006
Camille Dreyfus Teacher-Scholar Award, 2004
Dow Corning Assistant Professorship - University of Michigan, 2002
Otto-Hahn medal 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

1. Walter, N.G. and Al-Hashimi, H.M., "RNA dynamics: it is about time", Curr. Opin. Struct. Biol., 2008, 18, 321-329. Editorial can be found in Curr. Opin. Struct. Biol., 2009, 18, 279-281.

2. Walter, N.G., Huang, C.-Y., Manzo, A.J., and Sobhy, M.A., "Do-it-yourself guide: How to use the modern single-molecule toolkit", Nat. Methods, 2008, 5, 475-489. Editorial can be found in Nat. Methods, 2008, 5, 457.

3. Walter, N.G., "Ribozyme Catalysis revisited: Is water involved?", Mol.Cell., 2007, 28, 923-929.

4. Hoerter, J.A.H., Walter, N.G., "Chemical Modification Resolves the Asymmetry of siRNA Strand Degredation in Human Blood Serum", RNA, 2007, 13, 1887.

5. Sefcikova, J., Krasovska, M.V., Sponer, J., Walter, N.G., "The Genomic HDV Ribozyme Utilizes a Previously Unnoticed U-turn Motif to Accomplish Fast Site-Specific Catalysis", Nucleic Acids Res., 2007, 35, 1933.

6. Tinsley, R.A.,Furchak, J.R.W., Walter, N.G., "Trans-Acting glmS Catalytic Roboswitch:Locked and Loaded", RNA, 2007, 13, 468.

7. Rhodes, M.M., Reblova, K., Sponer, J., Walter, N.G., "Trapped Water Molecules are Essential to Structural Dynamics and Function of a Ribozyme", Proc. Natl. Acad. Sci. USA, 2006, 103, 13381.

Click here for a complete list of Dr. Walter's publications