Joined the Department in 2015
- B.S., 2002 College of Life Sciences, Inner Mongolia University, China, Microbiology
- Ph.D., 2007 College of Life Sciences, Peking University, China, Biochemistry and Molecular Biology.
- Postdoctoral research, University of California, Berkeley
Editor of Research in Microbiology & Frontiers in Microbiology
Member of the American Society of Microbiology
How does a cell establish its shape? While spheres are favored by physical laws, cells are rarely spherical. Instead, many cells employ intricate molecular machineries and complex regulatory networks to build and maintain various shapes for diverse biological functions. Morphogenesis (the ability to build defined cell shapes) is especially important for bacteria, because bacterial cell shapes are usually defined by the peptidoglycan (PG) cell wall, an exoskeleton also essential for their survival. Since the machineries for PG synthesis constitute the best targets for antibiotics, understanding bacterial morphogenesis will provide critical information for the control of infectious diseases. To understand morphogenesis, we are investigating how bacteria form rods, the simplest non-spherical shapes.
- An exceptional model organism. When induced by chemicals, rod-shaped vegetative cells of the Gram-negative bacterium Myxococcus xanthus thoroughly degrade their cell wall and shrink into spherical spores. As these spores germinate, rod- shaped cells rebuild cell wall without preexisting templates, which provides a rare opportunity to visualize de novo cell wall synthesis and bacterial morphogenesis. Using M. xanthus as the model organism, we visualize cell wall synthesis using fluorescent dyes, label key components in the cell wall synthesis machinery with fluorescent tags, and investigate how spherical spores build rod- shaped cell wall through germination.
- A powerful technique. Because of the diffraction limit of visible light, the resolution limit for con- ventional light microscopy is 200-250 nm. For this reason, the localization and dynamics of single molecules cannot be resolved in bacterial cells. To solve this problem, we have built a super-resolu- tion microscope for single-particle tracking pho- toactivatable localization microscopy (sptPALM) and stochastic optical reconstruction microscopy (STORM). Most importantly, we are able to track single-particle dynamics in live cells at 10-ms inter- vals (100 frames/second).
The Innovations and Discoveries
- We found that germinating spores first synthesize cell wall on spherical surfaces in an isotropic manner, then elongate into rods by growing cell wall at nonpolar regions. Spores establish different shapes by altering the distribution pattern of their cell wall synthesis machineries, which in turn, alters the growth pattern of cell wall.
- Special protein regulators survey the status of cell wall synthesis in germinating spores and trigger the switch of growth pattern through a system including a cytoskeleton and molecular motor.
- We are now able to weaken bacterial cell walls and generate different cell shapes by manipulating the above system, which could usher in novel methods for the control of bacterial infection.
- Zhang, H, Venkatesan, S, Nan, B. Myxococcus xanthus as a Model Organism for Peptidoglycan Assembly and Bacterial Morphogenesis. Microorganisms. 2021;9 (5):. doi: 10.3390/microorganisms9050916. PubMed PMID:33923279 PubMed Central PMC8144978.
- Wong, GCL, Antani, JD, Lele, PP, Chen, J, Nan, B, Kühn, MJ et al.. Roadmap on emerging concepts in the physical biology of bacterial biofilms: from surface sensing to community formation. Phys Biol. 2021;18 (5):. doi: 10.1088/1478-3975/abdc0e. PubMed PMID:33462162 PubMed Central PMC8506656.
- Zhang, H, Mulholland, GA, Seef, S, Zhu, S, Liu, J, Mignot, T et al.. Establishing rod shape from spherical, peptidoglycan-deficient bacterial spores. Proc Natl Acad Sci U S A. 2020;117 (25):14444-14452. doi: 10.1073/pnas.2001384117. PubMed PMID:32513721 PubMed Central PMC7321990.
- Iadarola, DM, Basu Ball, W, Trivedi, PP, Fu, G, Nan, B, Gohil, VM et al.. Vps39 is required for ethanolamine-stimulated elevation in mitochondrial phosphatidylethanolamine. Biochim Biophys Acta Mol Cell Biol Lipids. 2020;1865 (6):158655. doi: 10.1016/j.bbalip.2020.158655. PubMed PMID:32058032 PubMed Central PMC7209980.
- Tchoufag, J, Ghosh, P, Pogue, CB, Nan, B, Mandadapu, KK. Mechanisms for bacterial gliding motility on soft substrates. Proc Natl Acad Sci U S A. 2019;116 (50):25087-25096. doi: 10.1073/pnas.1914678116. PubMed PMID:31767758 PubMed Central PMC6911197.
- Wright, TA, Jiang, L, Park, JJ, Anderson, WA, Chen, G, Hallberg, ZF et al.. Second messengers and divergent HD-GYP phosphodiesterases regulate 3',3'-cGAMP signaling. Mol Microbiol. 2020;113 (1):222-236. doi: 10.1111/mmi.14412. PubMed PMID:31665539 PubMed Central PMC7209772.
- Fang, Y, Lian, X, Huang, Y, Fu, G, Xiao, Z, Wang, Q et al.. Investigating Subcellular Compartment Targeting Effect of Porous Coordination Cages for Enhancing Cancer Nanotherapy. Small. 2018;14 (47):e1802709. doi: 10.1002/smll.201802709. PubMed PMID:30222252 PubMed Central PMC6563816.
- Fu, G, Bandaria, JN, Le Gall, AV, Fan, X, Yildiz, A, Mignot, T et al.. MotAB-like machinery drives the movement of MreB filaments during bacterial gliding motility. Proc Natl Acad Sci U S A. 2018;115 (10):2484-2489. doi: 10.1073/pnas.1716441115. PubMed PMID:29463706 PubMed Central PMC5877941.
- Pogue, CB, Zhou, T, Nan, B. PlpA, a PilZ-like protein, regulates directed motility of the bacterium Myxococcus xanthus. Mol Microbiol. 2018;107 (2):214-228. doi: 10.1111/mmi.13878. PubMed PMID:29127741 .
- Nan, B. Bacterial Gliding Motility: Rolling Out a Consensus Model. Curr Biol. 2017;27 (4):R154-R156. doi: 10.1016/j.cub.2016.12.035. PubMed PMID:28222296 .