Jun Liu, Ph.D.
1998, Chinese Academy of Sciences
The University of Texas Health Science Center at Houston
Medical School
Department of Pathology and Laboratory Medicine
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Jun Liu, Ph.D. 1998, Chinese Academy of Sciences The University of Texas Health Science Center at Houston |
Research Interests:
Infectious diseases continue to adversely effect human health, and despite significant advances in medical science, they remain the leading cause of death. Our long-term goal is to open the venue to the understanding the molecular basis of infectious diseases by studying the three-dimensional structural organization of living pathogens (including bacteria and viruses).
Cryo-electron tomography (Cryo-ET) has recently emerged as a 3-D imaging technique to bridge the information gap between X-ray crystallographic and optical microscopic methods to describe cellular and subcellular structures and their organization which orchestrate cellular life. Cryo-ET has become even more informative by supplementing this technology with 3-D averaging and classification, which significantly enhance the resolution and consequently our understanding of cellular processes. Recently we have utilized this methodology to determine the structural and conformational changes that occur upon the binding of the envelope glycoprotein (Env) of Human Immunodeficiency virus (HIV) to its cell surface receptor (CD4) [Liu et al. 2008 Nature]. The binding of Env to CD4 results in a major reorganization of the Env trimer and a closer contact between the virus and target cell and its co-receptor. This result will enhance the development of new strategies to combat HIV/AIDS.
My laboratory has also focused on Borrelia burgdorferi and its periplasmic flagella as a model system to study the flagellar structure and motility in situ. B. burgdorferi belongs to a group of bacteria, called spirochetes, which are related to major diseases in humans: syphilis (Treponema pallidum), Lyme disease (Borrelia burgdorferi), and leptospirosis (Leptospira interrogans). Motility is an essential component of the pathogenesis of these and other bacteria and the motor is considered to be a proficient biological machine for this purpose. We propose to determine the structures of the motor assembly associated with intact, functioning bacteria in situ by applying high-throughput cryo-ET and the most sophisticated image analysis available. Moreover, by complementing the structural work with genetic and functional analyses, we will be able to better understand the molecular basis of flagellar motility of B. burgdorferi. And the synergism provided by the methods is expected to establish the foundation for the design of future innovative drug strategies.
Most importantly, the novel techniques and practical training utilized in this project will foster an in-depth understanding of a variety of human pathogens (for example, HIV & TB) and offer a wide spectrum of important biomedical information at molecular resolution in living cell.
Depending on the student’s interests, a tutorial in my laboratory would provide experience with high throughput cryo-electron tomography, image processing and other interdisciplinary techniques in virology, molecular biology and structural biology.
Selected Publications:
Liu J, Bartesaghi A, Borgnia M, Sapiro G, Subramaniam S: Structure of native HIV-1 gp120 trimers in unliganded and CD4-liganded states. Nature, 2008 Jul 30. [Epub ahead of print]
Liu J, McBride MJ, Subramaniam S (2007) Cell-surface filaments of the gliding bacterium Flavobacterium johnsoniae revealed by cryo-electron tomography. J Bacteriol. 189:7503-7506.
Liu J, Taylor DW, Krementsova EB, Trybus KM, Taylor KA (2006) Three-dimensional structure of the myosin V inhibited state by cryoelectron tomography. Nature. 442:208-211.
Liu J, Wu S, Reedy MC, Winkler H, Lucaveche C, Cheng Y, Reedy MK, Taylor KA (2006) Electron tomography of swollen rigor fibers of insect flight muscle reveals a short and variably angled S2 domain. J Mol Biol. 362:844-860.
Program Affiliation:
Program in Molecular Pathology