Welcome to the Sai Lab!
My lab focuses on cryo-electron tomography (cryo-ET) and its application in in-situ structural biology, especially in emerging enveloped viruses.
We aim at bridging dimensions between sub-nanometer resolution structures to micrometer scale in in-situ landscapes, a soaring demand in the field of structural biology. To achieve this, we are active in developing cryo-ET methods, including: 1) High throughput cryo-ET and subtomogram averaging at near-atomic resolution; 2) Focused-ion beam milling of cryo samples (cryo-FIB-SEM) and 3) Correlative light and electron microscopy (CLEM).
Among the vast applications, we primarily study the emerging enveloped viruses, which are the most threatening pathogens to the public health nowadays. Most enveloped viruses are pleomorphic and impose great challenge for structural biology, cryo-ET and subtomogram averaging are the primary methods in solving their native structures. We aim to shed light on: how are these viruses assembled, and how do they disassemble through membrane fusion, where are their weaknesses?
🔥 HIGHLIGHT · LATEST PUBLICATION
Cryo-ET of IgG bivalent binding on SARS-CoV-2 provides structural basis for antibody avidity
Nature Communications, April 11, 2026
✨ Key findings: The bivalent nature of IgG antibodies can enhance its neutralization potency against enveloped viruses; however, on-virion structural details of IgG bivalent binding with antigens remain elusive. Here we investigate how two potent IgGs P17 and S309 interact with S-trimers on the SARS-CoV-2 surface by cryo-ET. We find both IgGs exploit the mobility of S-trimers to form diverse configurations of S-IgG dimer-of-trimers, which oligomerize into higher-order patterns. Specifically, P17 stabilizes S-trimers into linear assemblies within minutes, whereas S309 primarily stabilizes S-trimer into circular assemblies that extend into lattice-like structures. Both assembly patterns effectively activate complement cascade. Additionally, both IgGs can facilitate inter-virion coupling through bivalent binding of opposing S-trimers, potentially enhancing immune recognition and clearance. These findings establish a structural framework for understanding IgG avidity in neutralizing enveloped viruses and offer valuable insights for antibody engineering and vaccine design.