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Nils Walter

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Primary Appointment: LSA Chemistry
Primary PIBS Dept.: Biophysics
Other PIBS Depts.: Bioinformatics
PubMed Name: Walter NG
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 DESCRIPTION OF RESEARCH
  At the interface of Chemistry and Biology, a recent revolution has 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 intervention approaches. Our group's goal is to understand the structure-function relationships in these ncRNAs and then utilize them for biomedical, bioanalytical and nanotechnological applications. The ncRNAs 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 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 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 is given below.

1. 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.

2. Utilizing single molecule fluorescence imaging techniques to follow movement of the ribosome on a secondary structured mRNA.

3. Utilizing single molecule fluorescence imaging techniques in nanotechnology to follow autonomously moving engineered "molecular spiders."

4. 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.

5. Using single-molecule fluorescence techniques to observe in unprecedented detail fluctuations of single ribozyme molecules between catalytically active and inactive conformations.