Unveiling the Microscopic World: Hong Zhou's Pioneering Research at UCLA

Introduction

At the University of California, Los Angeles (UCLA), a leading public university, Dr. Z. Hong Zhou leads a groundbreaking research lab that delves into the intricate world of biological complexes. By employing cutting-edge techniques such as cryogenic electron microscopy (cryoEM) and cryogenic electron tomography (cryoET), Dr. Zhou and his team are visualizing these complexes with unprecedented detail, furthering our understanding of their function and organization. Dr. Zhou's work combines structural biology, microbiology, computational biology, and bioinformatics to address fundamental questions in biology.

The Electron Imaging Center for NanoMachines (EICN)

Dr. Zhou is also the founding director of the Electron Imaging Center for NanoMachines (EICN) at the California Nanosystems Institute (CNSI). This center serves as a hub for advancing electron microscopy techniques and fostering interdisciplinary collaboration.

Cryo-Electron Microscopy: A Window into Biological Structures

CryoEM and cryoET are powerful tools that allow scientists to visualize biological samples in their native state, without the need for staining or fixation. This is achieved by rapidly freezing the samples at cryogenic temperatures and then imaging them with an electron microscope. The resulting images can then be processed using sophisticated computational methods to generate high-resolution three-dimensional models of the biological complexes.

The use of cryogenic electron microscopy (cryoEM) and cryogenic electron tomography (cryoET) to visualize biological complexes allows Dr. Zhou to gain unprecedented insight into the mechanisms of infection by creating some of the world’s most detailed 3-D models of viruses, bacteria, and other biological complexes.

Deciphering Viral Structures and Infection Mechanisms

Dr. Zhou's research has made significant contributions to our understanding of viral structures and infection mechanisms. His lab achieved the first atomic structural model of a herpesvirus capsid, the protein shell surrounding a virus's nucleic acid. This breakthrough has significant implications for the development of new therapies. The virus he modeled is ubiquitous, maintains long-term latency, and possesses great genetic capacity, leading researchers to believe it could be used for gene delivery, oncolytic vectors, and vaccinations against other herpesviruses and even HIV/AIDS. Dr. Zhou’s models will guide the design of these therapeutic possibilities.

Key Publications:

Gong D, Dai X, Jih J, Liu YT, Bi GQ, Sun R, Zhou ZH. (2019) DNA-Packing Portal and Capsid- Associated Tegument Complexes in the Tumor Herpesvirus KSHV. Cell. 178(6):1329-1343.e12. doi: 10.1016/j.cell.2019.07.035. This publication details the structure of the DNA-packing portal and capsid-associated tegument complexes in the Kaposi's sarcoma-associated herpesvirus (KSHV), a tumor herpesvirus.
Liu, W., Y. Cui, C. Wang, Z. Li, D. Gong, X. Dai, G. Q. Bi, R. Sun and ZH Zhou* (2020). Structures of capsid and capsid-associated tegument complex inside the Epstein-Barr virus. Nat Microbiol 5, 1285-1298, doi:10.1038/s41564-020-0758-1. This study presents the structures of the capsid and capsid-associated tegument complex inside the Epstein-Barr virus, providing insights into the virus's assembly and infection mechanisms.
Zhou K, Si Z, Tso J, Luo M, Zhou ZH* (2022) Atomic model of vesicular stomatitis virus and mechanism of assembly. Nat Commun.13(1):5980. doi: 10.1038/s41467-022-33664-4. This paper describes the atomic model of the vesicular stomatitis virus and elucidates the mechanism of its assembly.

Uncovering the Secrets of Ribosomes and Antibiotic Resistance

Dr. Zhou and his team have also made significant contributions to our understanding of ribosomes, the molecular machines responsible for protein synthesis. By comparing atomic resolution models of human ribosomes and parasite ribosomes, they revealed a parasite-specific structure that antibiotics target. This finding gave researchers a new structural basis for developing novel, and potentially more effective, antibiotics.

Elucidating the Telomerase Structure

The Zhou lab has also studied telomerase, an enzyme crucial for maintaining the integrity of chromosomes during cell division.

Key Publications:

He, Y., Y. Wang, B. Liu, C. Helmling, L. Susac, R. Cheng, Z.H. Zhou* and J. Feigon* (2021). Structures of telomerase at several steps of telomere repeat synthesis. Nature 593(7859): 454- 459. doi: 10.1038/s41586-021-03529-9. This publication details the structures of telomerase at several steps of telomere repeat synthesis, providing insights into the mechanism of telomere maintenance.

Splicing Mechanisms

Key Publications:

Li X, Liu S, Zhang L, Issaian A, Hill RC, Espinosa S, Shi S, Cui Y, Kappel K, Das R, Hansen KC, Zhou ZH, Zhao R. 2019. A unified mechanism for intron and exon definition and back-splicing. Nature 573, 375-380 doi:10.1038/s41586-019-1523-6. The study provides insights into the mechanisms of intron and exon definition and back-splicing.

A Personal Motivation

Dr. Zhou’s path to studying viruses was deeply personal. He was training in atomic physics when a virus took his mother’s life and inspired him to study-and fight-infection. This personal experience fuels his passion for research and his commitment to finding new ways to combat viral diseases.

Pushing the Boundaries of Scientific Exploration

Dr. Zhou believes we can push the limits of our measuring tools and techniques by combining cryo-electron microscopy, particle physics, and bioinformatics. He hopes cryo-electron microscopy leads to a future where we can study human cells in as much detail as we study virus cells.

The Ubiquity of Herpesviruses

"Why do I study herpes? We all have it; it is part of us, it has always been a part of us, and it will probably be part of us for years to come," says Dr. Zhou, highlighting the importance of understanding these ubiquitous viruses.

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