Current projects

① High-resolution cryoEM Reconstruction of Large Complexes
              Project number: 5R01GM071940-15
We aim to develop methods to efficiently determine, at atomic-resolution, three-dimensional (3D) structures of large biological complexes through cryoEM. In recent years, we have witnessed a drastic transformation of the field of structural biology, popularly referred to as “the cryoEM revolution”. 

Our lab has developed novel imaging and processing methods and validated these methods by determining in situ structures of important—and sometimes fundamental—biological processes in large icosahedral and helical complexes, as well as atomic models of purified protein-nucleic acid complexes and membrane proteins that have been resistant to previous X-ray crystallography and NMR efforts. 

Moving forward, we will continue developing novel computational methods for sub-particle refinement and nucleic acid modeling, specifically cryoID, an integrative software package that allows near-atomic resolution cryoEM structures from many complexes in enriched cellular milieu to be determined, identified, and atomically modeled. Our lab’s aims moving forward with this research theme are the following: 
(Aim 1) sub-particle reconstructions and refinement for in situ atomic structures in large deformable or intrinsically structurally heterogeneous complexes such as those in large enveloped viruses and native cellular complexes (e.g., helical assemblies); 
(Aim 2) modeling genome structures in both RNA and DNA viruses, as well as cellular transcriptional/replicative complexes
(Aim 3) validating these new methods for atomic structure determination by application to red blood cell proteome, translocon bacteriocin nano-machines and membrane protein complexes,helical filamentous cellular (e.g., actin and axoneme) and viral assemblies
(Aim 4)genome structures inside a number of ssRNA, dsRNA and dsDNA viruses. 

A successful outcome of this renewal project will further advance cryoEM in structural studies of large complexes and will have a great impact on many areas of biomedical research.

Select publications:

Structural basis of HIV-1 Vif-mediated E3 ligase targeting of host APOBEC3H.
Ito, F., Alvarez-Cabrera, A. L., Kim, K., Zhou, Z. H. & Chen, X. S. (2023). Nature Communications
Structure of LARP7 Protein p65–telomerase RNA Complex in Telomerase Revealed by Cryo-EM and NMR.
Wang, Y., He, Y., Wang, Y., Yang, Y., Singh, M., Eichhorn, C. D., Cheng, X., Jiang, Y. X., Zhou, Z. H. & Feigon, J. (2023). Journal of Molecular Biology
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
Resolving the Preferred Orientation Problem in CryoEM Reconstruction with Self-Supervised Deep Learning.
Liu, Y.-T., Hu, J. & Zhou, Z. H. (2023). Microscopy and Microanalysis

Research & Facilities 

Zhou Lab
California Nanosystems Institute (CNSI)
University of California Los Angeles (UCLA)
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