Zhixin Lyu, Ph.D.
Professional Experience
- Staff Scientist, NIDDK, NIH, 2023-present
- Research Associate, Johns Hopkins School of Medicine, 2021-2023
- Postdoctoral Fellow, Johns Hopkins School of Medicine, 2015-2021
- Ph.D., Peking University, China, 2014
- B.S., Wuhan University, China, 2009
Current Research
Gram-negative bacteria possess an outer membrane that serves as both a protective barrier and the first point of contact with the host. Embedded within this membrane are β-barrel outer membrane proteins (OMPs), which perform essential functions such as nutrient uptake, antibiotic efflux, and host–pathogen interactions. OMPs are synthesized in the cytoplasm, translocated across the inner membrane, and delivered to the periplasm, where chaperones including SurA and Skp prevent aggregation and misfolding. They are subsequently targeted to the β-barrel assembly machinery (BAM) complex, which catalyzes their folding and insertion into the outer membrane. Recent cryo-electron microscopy (cryo-EM) studies have captured multiple conformations of the OMP–BAM complex, providing a structural framework for BAM-mediated folding. However, these snapshots do not reveal the dynamic mechanism by which OMPs fold and assemble.
To overcome this limitation, we employ single-molecule Förster resonance energy transfer (smFRET), which monitors conformational changes by measuring distance variations between fluorophores, together with the anti-Brownian electrokinetic (ABEL) trap, which enables extended observation of individual molecules in solution without immobilization. By integrating these approaches, we aim to capture the earliest interactions between OMPs and the BAM complex and to map their folding trajectories in real time. This strategy will provide critical insights into the dynamic mechanism of OMP biogenesis, a process fundamental to bacterial physiology and an attractive target for the development of novel antibiotics.
Select Publications
- FtsZ-mediated spatial-temporal control over septal cell wall synthesis.
- Hu L, Perez AJ, Nesterova T, Lyu Z, Yahashiri A, Weiss DS, Xiao J, Liu J.
- Proc Natl Acad Sci U S A (2025 Jul 8) 122:e2426431122. Abstract/Full Text
- Third track model for coordination of septal peptidoglycan synthesis and degradation by FtsN in Escherichia coli.
- Lyu Z, Yang X, Yahashiri A, Ha S, McCausland JW, Chen X, Britton BM, Weiss DS, Xiao J.
- Nat Microbiol (2025 Jun) 10:1521-1534. Abstract/Full Text
Research in Plain Language
Outer membrane proteins (OMPs) are very important for Gram-negative bacteria, which have an extra protective layer around them. These proteins act like gatekeepers: they strengthen the outer membrane and control what goes in and out. In harmful bacteria, OMPs can even help them hide from the immune system and cause infections.
Learning how OMPs are built, a process called biogenesis, is important because it could lead to new ways to fight bacterial infections, especially since many bacteria are becoming resistant to antibiotics. With advanced tools like cryo-electron microscopy, scientists have been able to take snapshots of OMPs working with a helper machine called the BAM complex. But these snapshots do not explain how BAM actually helps OMPs fold and settle into the outer membrane. To answer this, we use special techniques such as smFRET and the ABEL-trap, which let us watch these proteins move and interact in real time. This research not only helps us better understand how bacteria build their protective shields but may also lead to new ways to combat infections.
Research Images
