Areas of Interest
At the interface of Biology and Chemistry, a revolution has recently taken place that has uncovered a plethora of small non-coding (nc)RNAs in our bodies, which outnumber protein-coding genes by several-fold, dominate the expression patterns of all genes in all cells, and have inspired entirely new therapeutic disease intervention approaches. Our group's goal is to understand the mechanistic structure-function relationships in these ncRNAs using single molecule tools and then utilize them for biomedical, bioanalytical and nanotechnological applications. The ncRNAs we study range from small RNA enzymes, 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 RNA interference machinery involved in gene regulation and virus suppression. In particular, we employ fluorescence techniques to study in real-time the kinetic mechanisms of these ncRNAs, in bulk solution, in live cells, and at the single-molecule level. Applications include the identification and optimization of ncRNAs for gene therapy and as novel biosensors and biomarkers, 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 biochemical, molecular biological, and biophysical approaches. An outline of several exciting current projects is given below.
1. Dissecting pre-mRNA splicing by fluorophore labeling individual RNA or protein components and following their fluorescence fluctuations during splicing in cell extracts by single molecule fluorescence microscopy.
2. Using single molecule fluorescence techniques to observe in unprecedented detail fluctuations of single ncRNA molecules between functionally active and inactive conformations.
3. Utilizing single molecule fluorescence imaging to follow movement of the ribosome on a secondary structured mRNA, including riboswitch motifs that utilize an aptamer domain to recognize a specific ligand and effect downstream gene expression.
4. Developing a model system for understanding gene silencing by directly observing, using fluorescence techniques, the action of small interfering (si)RNAs and micro (mi)RNAs on pathogenic mRNAs in cell extracts and live cells.
5. Utilizing super-resolution fluorescence imaging techniques in nanotechnology to follow and optimize autonomously moving engineered "molecular spiders" and the functionality of other RNA and DNA nanodevices.
Analytical Chemistry • Bioanalytical Chemistry • Bioinorganic Chemistry • Biophysical Chemistry • Chemical Biology • Energy Science • Nano Chemistry • Optics and Imaging • Organic Chemistry • Physical Chemistry • RNA Biochemistry • Sensor Science • Surface Chemistry • Sustainable Chemistry • Ultrafast Dynamics
Other Research Interests
- Single Molecule Fluorescence Spectroscopy and Microscopy
- Folding and Function of Non-Coding RNA
- Live-Cell Imaging
- Biophysical Chemistry of Nucleic Acids
Honors & Awards
2017 Francis S. Collins Collegiate Professor, University of Michigan
2017 Mid-Career Award, RNA Society
2015 Jean Dreyfus Boissevain Lecturer, Trinity University, San Antonio, TX
2015 Harold R. Johnson Diversity Service Award, University of Michigan
2013 Faculty Recognition Award, University of Michigan
2013 Imes and Moore Faculty Award, University of Michigan
2006 Alumnus of the Year Award, Sherbrooke RiboClub
2004 Camille Dreyfus Teacher-Scholar Award
1995 Otto-Hahn Award for Outstanding Researchers of the Max-Planck Society
1992 Anton Keller Prize for best Chemistry Diploma of the Year, Technical University of Darmstadt
2011 AAAS Fellow
2006 JILA Distinguished Visitor Fellowship (David Nesbitt group)
Feodor-Lynen Postdoctoral Research Fellowship, Alexander von Humboldt Foundation
Kekule Ph.D. Scholarship from the Stiftung Stipendienfonds des Verbandes der Chemischen Industrie
Study Scholarship from the Studienstiftung des Deutschen Volkes
2012 Visiting Scholar, Alexander von Humboldt Foundation
2011 ADVANCE Program for Executive Leadership, University of Michigan
2011 Buchanan Lecturer, Bowling Green State University
2009-13 MSFB Study Section Member, National Institutes of Health
2006 Visiting Scholar, Harvard University (Sunney Xie group)
2002 Dow Corning Assistant Professorship, University of Michigan
A guide to nucleic acid detection by single-molecule kinetic fingerprinting.
Johnson-Buck A, Li J, Tewari M, Walter NG.
Methods. 2019; 153: 3-12.
Ligand Modulates Cross-Coupling between Riboswitch Folding and Transcriptional Pausing.
Widom JR, Nedialkov YA, Rai V, Hayes RL, Brooks CL 3rd, Artsimovitch I, Walter NG.
Mol Cell. 2018; 72: 541-52.
Kinetics coming into focus: single-molecule microscopy of riboswitch dynamics.
Ray S, Chauvier A, Walter NG.
RNA Biol. 2018 Oct 17. [Epub ahead of print]
Ultraspecific and Amplification-Free Quantification of Mutant DNA by Single-Molecule Kinetic Fingerprinting.
Hayward SL, Lund PE, Kang Q, Johnson-Buck A, Tewari M, Walter NG.
J Am Chem Soc. 2018; 140: 11755-62.
Hierarchical mechanism of amino acid sensing by the T-box riboswitch.
Suddala KC, Cabello-Villegas J, Michnicka M, Marshall C, Nikonowicz EP, Walter NG.
Nat Commun. 2018; 9: 1896.
Exploring the speed limit of toehold exchange with a cartwheeling DNA acrobat.
Li J, Johnson-Buck A, Yang YR, Shih WM, Yan H, Walter NG.
Nat Nanotechnol. 2018; 13: 723-29.
Introduction-RNA: From Single Molecules to Medicine.
Walter NG, Maquat LE.
Chem Rev. 2018; 118: 4117-19.
For a list of publications from PubMed, click HERE