Nils G. Walter, Ph.D.

Professor, Chemistry
Professor, Biological Chemistry

2405 Chemistry

930 N. University Ave.

Ann Arbor, MI  48109-1055

 

(734) 615-2060

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.

Research Areas

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

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

Fellowships

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

Other Positions

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

Published Articles or Reviews

Recent Publications

Local-to-global signal transduction at the core of a Mn2+ sensing riboswitch.
Suddala KC, Price IR, Dandpat SS, Janeček M, Kührová P, Šponer J, Banáš P, Ke A, Walter NG.
Nat Commun. 2019; 10: 4304.

Versatile transcription control based on reversible dCas9 binding.
Widom JR, Rai V, Rohlman CE, Walter NG.
RNA. 2019, in press.

Biological Pathway Specificity in the Cell-Does Molecular Diversity Matter?
Walter NG.
Bioessays. 2019; 41: e1800244.

Probing RNA structure and interaction dynamics at the single molecule level.
Chauvier A, Cabello-Villegas J, Walter NG.
Methods. 2019; 162-163: 3-11.

Dynamic Recruitment of Single RNAs to Processing Bodies Depends on RNA Functionality.
Pitchiaya S, Mourao MDA, Jalihal AP, Xiao L, Jiang X, Chinnaiyan AM, Schnell S, Walter NG.
Mol Cell. 2019; 74: 521-33.

Coming Together: RNAs and Proteins Assemble under the Single-Molecule Fluorescence Microscope.
Jalihal AP, Lund PE, Walter NG.
Cold Spring Harb Perspect Biol. 2019; 11: a032441.

Quantitative Mapping of Endosomal DNA Processing by Single Molecule Counting.
Prakash V, Tsekouras K, Venkatachalapathy M, Heinicke L, Pressé S, Walter NG, Krishnan Y.
Angew Chem Int Ed Engl. 2019; 58: 3073-76.

Single-Molecule Kinetic Fingerprinting for the Ultrasensitive Detection of Small Molecules with Aptasensors.
Weng R, Lou S, Li L, Zhang Y, Qiu J, Su X, Qian Y, Walter NG.
Anal Chem. 2019; 91: 1424-31.

For a list of publications from PubMed, click HERE

Web Sites