Cryogenic Electron Tomography (CryoET)

Cryogenic electron tomography (cryoET) is a specialized form of electron microscopy which allows us visualize three-dimensional structures of biological specimens cryogenically preserved in their native state. Frozen-hydrated samples are loaded into a TEM and tilted through incremental stage movements, from -60° to +60° . A series of views is collected throughout this rotation and used to reconstruct a 3D map of the imaged area, termed a tomogram. 

In cryoEM, the orientation of the sample is invariant, and 2D projections of particles in different random orientations are used to compute a high-resolution average volume. CryoET allows us to directly visualise specimens in 3D from tomograms, making it uniquely suited for studying pleiomorphic biological structures such as viruses. However, TEM is limited to <500 nm sample thickness. Focused ion beam (FIB) milling technology allows us to carve out 100–250-nm-thin regions in vitrified cells and survey their architecture. 

CryoET is a powerful and emerging method wich our lab has an interest in developing, as well as applying to answer biological questions. Listed below are some of our works in this area.

Select publications:

Isotropic reconstruction for electron tomography with deep learning.
Liu, Y.-T., Zhang, H., Wang, H., Tao, C.-L., Bi, G.-Q. & Zhou, Z. H. (2022). Nature Communications
Atomic model of vesicular stomatitis virus and mechanism of assembly.
Zhou, K., Si, Z., Ge, P., Tsao, J., Luo, M. & Zhou, Z. H. (2022). Nature Communications
Mesophasic organization of GABAA receptors in hippocampal inhibitory synapses.
Liu, Y.-T., Tao, C.-L., Zhang, X., Xia, W., Shi, D.-Q., Qi, L., Xu, C., Sun, R., Li, X.-W., Lau, P.-M., Zhou, Z. H. & Bi, G.-Q. (2020). Nature Neuroscience
Structure of the trypanosome paraflagellar rod and insights into non-planar motility of eukaryotic cells.
Zhang, J., Wang, H., Imhof, S., Zhou, X., Liao, S., Atanasov, I., Hui, W. H., Hill, K. L. & Zhou, Z. H. (2021) Cell Discovery
Locations and in situ structure of the polymerase complex inside the virion of vesicular stomatitis virus.
Si, Z., Zhou, K., Tsao, J., Luo, M. & Zhou, Z. H. (2022). Proceedings of the National Academy of Sciences
FAP106 is an interaction hub for assembling microtubule inner proteins at the cilium inner junction.
Shimogawa, M. M., Wijono, A. S., Wang, H., Zhang, J., Sha, J., Szombathy, N., Vadakkan, S., Pelayo, P., Jonnalagadda, K., Wohlschlegel, J., Zhou, Z. H. & Hill, K. L. (2023). Nature Communications

Cellular Architecture of Treponema pallidum: Novel Flagellum, Periplasmic Cone, and Cell Envelope as Revealed by Cryo Electron Tomography.
Liu, J., Howell, J. K., Bradley, S. D., Zheng, Y., Zhou, Z. H. & Norris, S. J. (2010). Journal of Molecular Biology
Postsynaptic protein organization revealed by electron microscopy.
Liu, Y.-T., Tao, C.-L., Lau, P.-M., Zhou, Z. H. & Bi, G.-Q. (2019). Current Opinion in Structural Biology
Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity.
Tao, C.-L., Liu, Y.-T., Zhou, Z. H., Lau, P.-M. & Bi, G.-Q. (2018). Frontiers in Neuroanatomy

Research & Facilities 

Zhou Lab
California Nanosystems Institute (CNSI)
University of California Los Angeles (UCLA)
 Email    |      Twitter    |      Google Scholar

Website related enquiries