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  • Chunyan Wang, PhD

    In the Liu lab, I am utilizing single particle cryo-EM analysis and cryo-electron tomography to study the conformational changes of ejection proteins during genome ejection in phages T7 and P22. By combining these state-of-the-art techniques with extensive knowledge from biochemical and genetic studies, we aim to reveal the molecular mechanisms of ejection protein remodeling during genome ejection. Our findings provide detailed structural and functional insights into phage infection.

    Efficient genome ejection is a critical yet little understood step in phage infection and requires large conformational changes in the mature tail machine. Specifically, podophages possess short tails that cannot span the Gram-negative cell envelope to allow direct genome ejection into the cell cytoplasm. These phages contain ejection proteins present in the mature capsid, possibly in complex with the genomic dsDNA. As the tail machine changes conformation after productive adsorption, these ejection proteins relocate inside the host bacteria, where they spontaneously assemble, forming a conduit for DNA translocation across the entire cell envelope. By contrast, the ejection proteins of podophages T7 and P22 have different conformations inside mature phages, both assembling a trans-envelope channel during genome ejection (Hu et al, 2013; Wang et al, 2019) using distinct mechanisms.

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  • Shoichi Tachiyama, PhD

    The cytoplasmic domain of MxiG interacts with MxiK and directs assembly of the sorting platform in the Shigella type III secretion system.

    Shoichi Tachiyama‡, Yunjie Chang§,¶, Meenakumari Muthuramalingam , Bo Hu**, Michael L. Barta 1, Wendy L. Picking‡‡, Jun Liu§,¶2 and William D. Picking‡,‡‡3

    From Fig 6: Surface rendering images of Shigella T3SS. Left) The overall architecture of T3SS is described by four main components; the cytoplasmic sorting platform (cytoplasmic side), basal body (between bacterial inner membrane, IM, and outer membrane, OM), needle (extended from the basal body), and tip complex (end of the needle). Right) Cryo-ET provided a view from IM side of T3SS. The cytoplasmic sorting platform and basal body form different numbers of symmetrical rings .

  • Wangbiao (Seven) Guo, PhD

    The flagellar motor is a powerful biological nanomachine that drives motility, and thus infectivity and survival, in bacteria. It is the only known molecular machine that can rotate bidirectionally – in both clockwise (CW) and counterclockwise (CCW) senses. Motor rotation relies on the passage of ions through inner membrane-embedded stator units to power the cytoplasmic switch complex (C-ring), thus generating torque. Despite decades of intensive research, the detailed mechanisms that underlie torque generation and directional switching are unclear. I joined the Liu lab to use cryo-electron tomography (cryo-ET) to study this sophisticated mechanism in the model system of the Lyme disease-causing spirochete Borrelia burgdorferi. Our high-resolution analysis of dynamic stator-C-ring interactions will reveal molecular mechanisms responsible for torque generation and rotational switching in the bacterial flagellar motor. In addition, I currently oversee the operation of our state-of-the-art cryo-focused ion beam (FIB) microscope, Aquilos2, which enables extraordinary high-throughput imaging to address diverse biological questions.

    Figure: Cryo-FIB milling of the Gram-negative bacterium Proteus in swarming conditions reveals the in-situ structure of the flagellar motor. (Left) Top view of scanning electron microscopy (SEM) image of Proteus swarming. (Right top) Side view of scanning electron microscopy (SEM) image of Proteus swarming. (Right bottom) Final lamella with 4o tilt.

    • Huaxin Yu, PhD

      Virus attachment and genome entry play a pivotal role in bacteriophage infection. I using cryo-ET to investigate how phage P22 initiates infection of Salmonella enterica. The high-resolution structure of the tail machine, including the icosahedral capsid, tail spike, membrane-spanning protein, and channel structure, have provided valuable insights into the phage P22 infection. Understanding the molecular mechanisms underlying this process is crucial to advance knowledge of bacteriophage-host interactions.

      Image (Huaxin Yu): Bacteriophage P22 capsid and tail spike infecting Salmonella enterica, visualized using cryo-ET.
    • Jian Yue, PhD

      The pathogenic bacterium Legionella pneumophila causes Legionnaires' disease by injecting a diverse array of proteins into host cells through the Dot/Icm type IV secretion system (T4SS). This elaborate nanomachine transports over 300 distinct protein effectors or toxins into eukaryotic host cells. My research focuses on utilizing high-throughput cryo-electron tomography (cryo-ET) in combination with other cutting-edge approaches to visualize and determine high-resolution 3D structures of this intricate nanomachine to reveal its transport mechanisms. This work holds great promise in advancing our understanding of T4SS macromolecular machines and their vital roles in various biological processes. Furthermore, knowledge gained from this study will open new avenues for the development of drugs and therapies combatting a wide range of infectious diseases.

      Image (Jian Yue, PhD): Construction of the structural model of the Legionella pneumophila Dot/Icm T4SS, including outer membrane-associated core complex (OMCC), plug, and inner membrane-associated complex (IMC)

    • Jack Botting, MS

      Flagellar motility is a crucial virulence factor in many disease-causing bacteria. Understanding the molecular mechanisms of flagellar motility is therefore vital to combatting microbial pathogenesis. While the flagellar motors of model organisms E. coli and S. enterica have been well characterized, more complex motors in H. pylori, B. burgdorferi, and V. cholerae, possess accessory structures that help such bacteria navigate challenging environments. Using cryo-ET, protein structure prediction, and molecular modeling, we can piece together the complex networks of proteins that make bacterial motility possible.

      Image (Jack Botting): A part of the flagellar motor required for motility in B. burgdorferi. Model generated from cryo-ET data and Alphafold-predicted protein structures using ChimeraX.
    • Samira Heydari

      I am investigating host-microbe interactions mediated by bacterial secretion systems, specifically type IV (T4SS), to determine their in-situ structure and dynamics. Secretion systems play a crucial role in pathogens by translocating virulence factors from the bacterial cytoplasm to the host cell. I am now using cryo-electron microscopy and microbiology techniques to solve how these specialized nanomachines are activated to inject molecular effectors and toxins into target cells.

      Image (Samira Heydari): Three-dimensional surface rendering of the outer membrane core complex (OMCC) of Cag T4SS in H.pylori, achieved using cryo-ET and subtomogram averaging.

    • Rajeev Kumar

      My research focuses on the molecular mechanisms underlying host-pathogen interactions. Motor proteins play a crucial role in the assembly and function of bacterial secretion machinery and are highly conserved in various secretion systems, including type III (T3SS) and type IV (T4SS). Specifically, I am investigating the ATPase complex, a key motor protein in T3SS. My research aims to reveal the structure and exact function of this dynamic protein complex, providing valuable insights for the development of novel antibiotics.

      Image (Rajeev Kumar): Cryo-ET vsualization of type IV pili (T4P) in Pseudomonas aeruginosa.

    Lab Alumni

    Erin McCrum, UT Houston Medical School, Postgraduate Fellow 2008

    Sherille Bradley, Texas State University, Visiting Undergraduate in Research 2009

    Xiaofeng Fu, Postdoctoral Fellow, 2010

    Gianmarco Raddi, Rice University, Visiting Undergraduate in Research 2010

    Charles Chen, Duke University, Visiting Undergraduate in Research 2010

    Yesha Zheng, Postdoctoral Fellow, 2011

    Dustin Morado, Georgia Tech, Visiting Undergraduate in Research 2010, 2011

    Sam Ruder, Rice University, Visiting Undergraduate in Research 2012

    Martin Chien, China Medical University, Taiwan, Visitor in Research 2012

    Sang (Michael) Xie, Clements High School, Student in Research 2012

    Hongyi Shi, Los Altos High School, Student in Research 2012

    Brian A. Tong, Bellaire High School, Student in Research 2010, 2011, 2012

    Alan Pan, Northwestern University, Summer intern 2012, 2013

    Xiaomin Li, Visiting Student, 2013

    Jonas Actor, University of Chicago, Summer intern 2014

    Qiang Chen, Visiting Student, 2014

    Jiagang Tu, Postdoctoral Fellow, 2012-2015

    Xiaowei Zhao, Postdoctoral Fellow, 2010-2015

    Wei-Ting Lin, Fu Jen Catholic University, Summer intern 2015

    Madeline Farley, Postdoctoral Fellow, 2015-2016

    Wendy Wang, Research Assistant, 2016-2017

    Dustin Morado, Research Assistant, 2010, 2011, 2014-2017

    Xiangan Liu, Research Assistant Professor 2015-2017

    David Burton, University of Montana, Visiting Undergraduate in Research 2017

    Jeffery Yang, Emory University, Visiting Undergraduate in Research 2017

    Bo Hu, Postdoctoral Fellow 2010-2016; Assistant Professor 2016-2017

    Tatsuro Nishikino, Nagoya University, Visitor in Research 2018

    Benjamin Crair, Guilford High School, Student in Research 2018, 2019

    Zhuan Qin, Postdoctoral Associate 2015-2019

    Meijing Li, Tshinghua University, Visiting Postgraduate Fellow 2018

    Wenwei Li, Postdoctoral Associate, 2017-2019

    Shiwei Zhu, Postdoctoral Associate, 2016-2019

    Pei Wang, Institute of Biophysics (Beijing), Visitor in Research, 2019

    Katherine Haney Gibson, University of Georgia, Visiting Undergraduate in Research, 2019

    Liuqi Zhu, Nantong University, Postgraduate Fellow, 2019

    Kevin Zhao, UCLA, Visiting Undergraduate in Research, 2019

    Xinrui Huang, Peking University, Visiting Associate Professor, 2018-2020

    Ze Li, Fudan University, Visiting Associate Professor, 2018-2020

    Wangbiao Guo, Zhejiang University, Postgraduate Fellow, 2019-2020

    Brittany Carroll, McGill University, Postdoctoral Associate, 2019-2021

    Meng Shao, Lab Assistant 2, 2019-2021

    Yunjie Chang, Postdoctoral Associate, 2017-2021

    Yue Lin (Cedric) Hu, Visiting Undergraduate in Research 2019, Postgraduate Associate 2021-2022

    Donghyun (Raphael) Park, Graduate Student 2017-2022

    Shuaiqi (Phil) Guo, Postdoctoral Associate/Associate Research Scientist, 2020 – 2023

    Liang Chen, Postgraduate Fellow, 2022 – 2023

    Chunyan Wang, Postdoctoral Associate/Associate Research Scientist, 2015 – 2024

    Ana Afonso, Postgraduate Fellow, 2023 – 2024