Francis S Collins Collegiate Professor of Chemistry, Biophysics, and Biological Chemistry
About
RNA Biophysical Chemistry at the Single-Molecule Level
In the biosciences, recent discoveries have unveiled a vast and functionally diverse world of non-coding RNAs (ncRNAs), which far outnumber protein-coding genes and play a dominant role in gene regulation. These insights have not only transformed our understanding of cellular processes but have also inspired novel therapeutic strategies.
Our collaborative, welcoming research group at the interface of Chemistry, Biology and Physics seeks to uncover the mechanistic structure-function relationships of these ncRNAs using single-molecule fluorescence techniques. By investigating how RNA molecules dynamically interact and function, we aim to advance applications in biomedicine, bioanalytics, and nanotechnology. Our studies range from small gene regulatory RNA motifs called riboswitches with potential therapeutic relevance to large RNA-protein complexes such as the RNA interference (RNAi) machinery, which governs gene silencing and antiviral defense. We employ cutting-edge fluorescence microscopy to track RNA behavior in live cells and at the single-molecule level, offering unprecedented real-time insights into RNA function.
Our interdisciplinary approach integrates chemistry, molecular biology, and biophysics, engaging students from diverse backgrounds and equipping them with a broad scientific skill set. By studying RNA molecules that exhibit rapid conformational changes over time scales ranging from microseconds to hours, we develop new tools for RNA-based therapeutics, biosensors, and drug discovery.
Current Research Directions:
-
Chembio: RNA Conformational Dynamics
- Using single-molecule fluorescence microscopy to observe how RNA molecules fluctuate between active and inactive conformations, providing insight into their regulatory roles.
-
Chembio: Riboswitch Structural Transitions
- Employing single-molecule fluorescence imaging and cryo-electron miceroscopy structure determination to study ligand-induced conformational changes in bacterial riboswitches, for the design of novel antibiotics.
-
Chembio: Mechanisms of RNAi and Gene Silencing
- Directly tracking the action of small interfering RNAs (siRNAs) and microRNAs (miRNAs) on pathogenic mRNAs in live cells, with potential therapeutic applications.
-
Analytical Chem: Biomarker Detection and Clinical Translation
- Developing ultrasensitive single-molecule counting technologies for detecting biomarkers, leading to the formation of a startup company focused on clinical diagnostics.
-
Materials Chem: Nanotechnology and Super-Resolution Imaging
-
PChem: Artificial Intelligence and Molecule Dynamics Simulations
- Analyzing and simulating complex single molecule behaviors at multiple scales using AI Foundation Moodels and Amber & CHARMM-based atomic simulations based on single molecule fluorescence and cryo-electron microscopy data.
Through our work, we aim to push the boundaries of RNA biophysics and contribute to the growing field of RNA-based medicine. That entails having founded both the Single Molecule Analysis in Real-Time (SMART) Center and the Center for RNA Biomedicine.
Full List of Publications
https://www.ncbi.nlm.nih.gov/myncbi/nils.walter.1/bibliography/public/?sortby=pubDate&sdirection=descending
https://scholar.google.com/citations?hl=en&user=1IG1j9gAAAAJ
Research Areas(s)
- 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 RNA
- Live-Cell Imaging
- Biophysical Chemistry of Nucleic Acids
- DNA Nanotechnology and Smart Materials
