Nils G. Walter, Ph.D.

At the interface of Biology and Chemistry, a revolution has recently taken place that has uncovered a plethora of small non-coding RNAs (ncRNAs) 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