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
FlyTomo: a streamlined software for on-the-fly cryo-ET data processing and diagnosis
Nature Communications, 2026
✨ Key findings:
Cryo-ET combined with subtomogram averaging (STA) enables the structural elucidation of macromolecular assemblies in native environments. However, their widespread adoption has been limited by the labor-intensive, expertise-dependent data processing workflow. Here we present FlyTomo, a software that streamlines data processing from frame alignment to STA with high-throughput for authentic cryo-ET scenarios. During data acquisition, FlyTomo performs real-time diagnosis, enabling prompt feedback on sample quality, microscope performance and structural features. After acquisition, it aggregates diagnostic metrics into an overview, guiding users through data review and refinement. FlyTomo also curates raw and processed data into directories to simplify data management and archiving. We validate FlyTomo across a diverse set of authentic cryo-ET samples, including purified enveloped viruses and cryo-lamellae, on multiple microscopes and cameras, achieving structures at resolutions of 3.4 to 7.3 Å. Collectively, by integrating accuracy, scalability and usability, FlyTomo reduces the technical barrier for in situ structural biology using cryo-ET.