Welcome to the Zhou Lab!
The Zhou Lab addresses fundamental, high-impact questions in cell biology and neuroscience by integrating mechanistic and functional studies with advanced structural approaches.
Our research focuses on protein–membrane assemblies in their native cellular environment, using cryo-electron tomography (cryo-ET). Cryo-ET enables high-resolution, three-dimensional visualization of macromolecular complexes and cellular ultrastructure directly within intact cells in a near-native state. Using this approach, we discovered that postsynaptic proteins are organized into PSD nanoblocks—modular subsynaptic units whose size, organization, and spatial distribution are dynamically regulated (JCB, 2025). These findings establish a new conceptual framework for understanding synaptic strength and plasticity.
In parallel, we develop protein-based tools for molecular-resolution cellular imaging through protein design and engineering. Our work advances labeling and imaging strategies for live-cell fluorescence microscopy and 3D cryo-ET, expanding the toolkit for visualizing and engineering cellular structures. We have developed a genetically encoded, EM-visible V-shaped tag (62 kDa) that enables single-molecule–resolution localization of proteins in cells using cryo-ET (bioRxiv, 2026).
Together, these efforts reflect our approach to identifying fundamental biological problems, developing cutting-edge structural methodologies, and translating molecular insights into conceptual and technological advances.
Current Research Directions
- Dual-visible EM/FM labeling technologies for time-resolved, single-molecule–resolution 3D cellular imaging
- Molecular mechanisms of synaptic transmission and neuronal plasticity in health and disease
- Cellular engineering and synthetic organelle design