Revolutionising structural biology with cryoEM and cryoFIB-SEM
Cryogenic Electron Microscopy (cryoEM), a Nobel Prize-winning technique, has revolutionised our understanding of biological structures at the molecular level, facilitating critical insights into health, disease, and biotechnology. However, its application has traditionally been limited by the necessity for extremely thin samples, often less than 200 nm in thickness, which constrains the study of larger biological specimens.
The introduction of the cryoFIB-SEM addresses this limitation by enabling precise milling of biological samples at cryogenic temperatures, producing ultra-thin lamellae that preserve the native context of complex and unique biological structures. The integration of fluorescence modules furthermore allows for accurate targeting of specific regions within a sample by using fluorescence signals to guide the milling process. This approach significantly enhances the precision and efficiency of the technique, enabling scientists to avoid unnecessary milling and preserve critical areas for their research.
Taken together, these advancements allow researchers to achieve near-atomic resolution imaging of proteins and other macromolecules within whole cells, unlocking unprecedented insights into cellular processes and interactions.
Dr. Thom Sharp, Principal Investigator and Associate Professor at the University of Bristol leading the successful BBSRC bid, elaborated on the transformative potential of this technology: “The new cryoFIB-SEM is a game-changer. Alongside making projects that were previously impossible, possible, the equipment will allow us to think up projects that we haven’t even conceived of before. This opens up a whole new world of opportunities to understand biology at the nanoscale. More than 35 researchers from across the GW4 Alliance provided projects and ideas for this grant, highlighting just how important this new equipment will become. My research group are already preparing to image immune defence in action, to understand how our immune system coordinates proteins to protect us against infections, with far-reaching consequences for human health and new treatments.”
Enhancing GW4’s world-leading cryoEM infrastructure
The cryoFIB-SEM will be integrated into the GW4 Facility for High-Resolution Electron Cryo-Microscopy, based at the University of Bristol, further strengthening the facility's role as a hub for cutting-edge structural biology research in Southwest UK. Since its opening in 2017, the GW4 cryoEM facility has enabled the determination of dozens of molecular structures, advancing research in critical areas such as human health and disease.
Complementing this acquisition, the University of Exeter has secured £1.1 million from the BBSRC to replace its current cryoEM with the latest generation entry-level screening microscope. This upgrade will ensure the continued support of the GW4 cryoEM pipeline, allowing for increased throughput and enhanced research capabilities across the alliance.
Dr. Vicki Gold, Chair of the GW4 Cryo-EM Steering Group and Associate Professor in Biosciences at the University of Exeter, emphasized the importance of this development: “We are absolutely delighted with this new funding award, which brings together over 20 academics and technical staff from across the GW4 region. It will open up exciting opportunities for groundbreaking research and ensure we continue to support and enhance the activity at the GW4 Regional Facility for CryoEM.”
Expanding training and research opportunities
The introduction of the cryoFIB-SEM coincides with expanded training opportunities within the GW4 cryoEM facility. Existing hands-on workshops for cryoEM sample preparation will be extended to include training on the new cryoFIB-SEM, ensuring that researchers gain practical experience with the latest advancements in the field.
In addition, the facility’s LUCID scheme (Limited Use for Collection of Initial Data) will be expanded to include access to the cryoFIB-SEM, providing researchers with the opportunity to explore novel projects and accelerate their entry into cryoET (cryogenic electron tomography).
Invitation to collaborate
The GW4 cryoEM facility invites academics and researchers worldwide to collaborate and explore the transformative potential of the new cryoFIB-SEM. By integrating this state-of-the-art technology with ongoing research efforts, the GW4 facility is poised to remain at the cutting edge of in situ structural biology, driving forward a deeper understanding of health and disease.
For further information and collaboration opportunities, please visit the GW4 facility website or contact us directly.