Advancements in Cryo-Electron Microscopy at Shanghai Institute of Organic Chemistry’s Research Center

Chinese scientists have achieved a breakthrough in structural biology by using cryo-electron microscopy (cryo-EM) to map biofilm-associated extracellular filaments at near-atomic resolution, offering new insights into bacterial communities and their resistance mechanisms. The research, published in Nature on April 28, 2026, was conducted at the Interdisciplinary Research Center on Biology and Chemistry (IRCBC) within the Shanghai Institute of Organic Chemistry (SIOC), part of the Chinese Academy of Sciences (CAS).

Atomic-Level Imaging of Biofilm Structures

The study provides the first ultrastructural and atomic characterization of extracellular filaments—long, thread-like proteins—produced by bacteria within biofilms. Biofilms are dense, surface-attached communities of microorganisms encased in a self-produced matrix, which protect bacteria from antibiotics, immune responses, and environmental stresses. These structures are a major factor in chronic infections, medical device contamination, and industrial biofouling.

Using cryo-EM, a technique that flash-freezes samples to preserve their native structure, the research team captured high-resolution images of the filaments, revealing their molecular architecture. The findings identify key protein subunits and their spatial arrangement, which may explain how biofilms maintain structural integrity and resist external threats. The study also highlights potential binding sites for therapeutic agents, suggesting new avenues for disrupting biofilm formation.

Collaborative Research and Technological Advancements

The project was led by researchers at the IRCBC, a joint initiative between SIOC and other CAS-affiliated institutions. The team collaborated with the Shanghai Advanced Research Institute’s National Facility for Protein Science, which houses state-of-the-art cryo-EM equipment. Earlier this year, the facility was recognized for its role in advancing structural biology research, including studies on protein misfolding and amyloid fibrils—abnormal protein aggregates linked to neurodegenerative diseases such as Parkinson’s and Alzheimer’s.

In January 2026, Mabwell, a Shanghai-based biopharmaceutical company, announced a partnership with SIOC and Shanghai Jiao Tong University to apply cryo-electron tomography (cryo-ET) in drug development. Cryo-ET, a related technique, allows scientists to visualize cellular structures in three dimensions at near-atomic resolution. The collaboration aims to accelerate the design of antibodies targeting misfolded proteins, building on the structural insights gained from cryo-EM studies.

Implications for Medicine and Industry

The Nature study’s findings could have significant implications for public health and biotechnology. Biofilms are responsible for an estimated 65% of microbial infections in humans, according to the U.S. National Institutes of Health, and are notoriously difficult to treat due to their resistance to conventional antibiotics. By mapping the extracellular filaments at atomic resolution, the research provides a foundation for developing targeted therapies that could weaken or dissolve biofilms without harming human cells.

In industrial settings, biofilms contribute to corrosion, clogging, and contamination in pipelines, water treatment systems, and food processing equipment. The study’s insights may inform the design of antimicrobial coatings or enzymatic treatments to prevent biofilm formation in these environments.

Broader Context in Structural Biology

The research aligns with China’s growing investment in structural biology and cryo-EM technology. In recent years, Chinese institutions have established multiple cryo-EM centers, including the National Facility for Protein Science in Shanghai and the Center for Excellence in Molecular Cell Science. These facilities have contributed to high-impact studies, such as the characterization of polymorphic amyloid fibrils associated with Parkinson’s disease, published in Proceedings of the National Academy of Sciences (PNAS).

The Shanghai Institute of Organic Chemistry has been at the forefront of interdisciplinary research, bridging chemistry and biology to address challenges in drug discovery, protein engineering, and disease mechanisms. The institute’s work on protein misfolding and amyloid fibrils has been cited in studies exploring the molecular basis of neurodegenerative disorders, further underscoring the importance of structural biology in understanding complex diseases.

Next Steps and Future Research

The researchers emphasized that while the study provides a detailed structural model of biofilm-associated filaments, further work is needed to validate potential drug targets. Future experiments may involve screening chemical compounds for their ability to disrupt filament assembly or testing the efficacy of biofilm-disrupting agents in animal models of infection.

The team also plans to explore the structural diversity of filaments across different bacterial species, as variations in protein composition could influence biofilm resilience and therapeutic responses. Such research could lead to species-specific treatments, reducing the risk of broad-spectrum antibiotic resistance.

As structural biology continues to advance, techniques like cryo-EM and cryo-ET are expected to play a pivotal role in unraveling the molecular mechanisms of disease and developing precision therapies. The latest findings from the Shanghai Institute of Organic Chemistry represent a critical step toward understanding—and ultimately combating—one of microbiology’s most persistent challenges.