The Zhuang research lab uses advanced optical imaging techniques to study the behavior of individual biological molecules and complexes in vitro and in live cells. Our current research is focused on the following three major directions.

 

Super-resolution optical imaging. We have developed a new form of high resolution light microscopy, stochastic optical reconstruction microscopy (STORM). Using STORM, we have achieved three-dimensional, multicolor fluorescence imaging of molecular complexes, cells and tissues with ~20 nm lateral and ~50 nm axial resolutions. We hope to advance STORM capabilities to ultimately enable real-time imaging of cells and tissues with resolution at the true molecular length scale.

 

Virus-cell interactions. We have developed real-time imaging methods to track individual virus particles in live cells. This approach allows us to follow the fate of individual viruses, to dissect the infection pathways into microscopic steps, and to determine the molecular mechanism of each step. Using this approach, we are investigating the entry and assembly mechanisms of influenza virus and poliovirus, as well as related cellular trafficking pathways.

 

Nucleic acid – protein interaction. We use single-molecule approaches to study nucleic acid-protein complexes. These experiments allow us to directly probe dynamic interactions between DNA, RNA and proteins within these complexes and thus to provide mechanistic understandings of these biomolecular processes. Specific systems being investigated include telomerase, HIV reverse transcriptase and chromatin remodeling enzymes.