Understanding the mechanisms of cellular function and their dysfunction in disease requires a detailed picture of the molecular interactions in cells. In particular, we need imaging tools with single-molecule sensitivity, molecular-scale resolution, and dynamic imaging capability to allow direct visualization of molecular interactions in cells, as well as tools that can simultaneously image large numbers of genes, ideally at the genome scale, to probe how collective actions of these molecules give rise to cellular and tissue functions.

Research in the Zhuang lab is aimed at developing such imaging methods and applying them to problems of biomedical interest. Students and postdoctoral fellows in the Zhuang laboratory apply their diverse backgrounds in chemistry, physics, biology, and engineering to develop novel imaging methods, and to exploit these tools to study a variety of interesting biological problems, ranging from molecular structures in cells to cellular organization in tissues.

We have developed a super-resolution imaging method, stochastic optical reconstruction microscopy (STORM), and are apply this method to study sub-cellular structures in neurons and chromatin structures in the nucleus. For example, we discovered a periodic membrane skeleton in neurons made of actin, spectrin and associated molecules, and currently studying the structure, function and disease implication of this structure.

We have recently developed a single-cell transcriptome imaging method, multiplexed error-robust FISH (MERFISH) and are applying this method to study the spatial organization of cells in the brain, as well as gene regulation at the genomic scale.