As the fundamental unit of life, a cell is comprised of numerous types of molecules that form intricate interaction networks. Dissecting the inner workings of a cell requires imaging with molecular-scale resolution such that molecular interactions can be directly visualized. However, the diffraction-limited resolution of light microscopy is substantially larger than molecular length scales in cells, making many sub-cellular structures difficult to visualize. Another major challenge in imaging is the low throughput in the number of molecular species that can be simultaneously imaged, while genomic-scale throughput (i.e. the ability to simultaneously image thousands of molecular species) is needed for addressing systems level questions. Here, I will describe two imaging methods that we developed to overcome these challenges, including STORM, a super-resolution imaging method that overcomes the diffraction limit and allows imaging of molecular structures in cells with nanometer-scale resolution, and MERFISH, an imaging method with genomic-scale throughput. I will also describe some recent biological discoveries enabled by these methods.
Prof. Xiaowei Zhuang is the David B. Arnold Professor of Science, Professor of Chemistry and Chemical Biology and Professor of Physics, Harvard University, Howard Hughes Medical Institute Investigator