Northern Eye - A Cryo-Electron Microscopy Resource in the North East

This application represents a joint bid from Newcastle, Northumbria, and Durham Universities to acquire a state-of-the-art cryogenic transmission electron microscope.

Cryo-electron microscopy (cryo-EM) is a powerful imaging method that has revolutionised structural biology, with rapid technology development over the last decade enabling the visualisation of dynamic and flexible biomacromolecules and assemblies.

Currently, there is no cryo-EM instrumentation in the North East of England, despite the region having research strengths and expertise in structural biology across the lead institutions. Our vision is to future-proof these North East institutions in next-generation cryo-EM. This proposal will equip the region with an indispensable tool to study dynamic macromolecular complexes that are not readily amenable to X-ray crystallography.

The proposed instrument is a new class of cryo-electron microscope that:

enables timely and efficient sample optimisation through real-time screening and preliminary analysis, thereby addressing a key bottleneck in the cryo-EM workflow;
is a user-friendly instrument for training structural biologists in cryo-EM, a highly valued skill set in academic and industrial careers;
is a cost-effective platform for building cryo-EM capability and expertise at the institution level.
The instrument will be housed within the Newcastle University Structural Biology Facility, that is already equipped with a suite of X-ray crystallography and IT resources. This Facility will therefore become a hub for North East researchers to pursue and collaborate on biomacromolecular structure determination for both fundamental and translational research. The instrument will be managed through an organisational structure of operational, strategic, and user groups, with representation from all three institutions, to ensure effective day-to-day operation and decision making.

The instrument user-base composes some 30 research groups from the three lead institutions, with a strong track record in studying diverse biomacromolecules across the kingdoms of life. The team of applicants also includes technology specialists with expertise in different applications of electron microscopy, as well as early-career researchers building their structural biology research portfolios. The instrument will enable research to advance the frontiers of molecular biosciences across the BBSRC strategic challenges of sustainable agriculture and food, renewable resources, and integrated understanding of human health.

We therefore request funds for the purchase of a 100 kV cryo-EM instrument with direct electron detector. While we will conduct a WTO compliant tender process, a microscope in this class is currently only available from ThermoFisher Scientific. We have engaged with them to test the microscope with our samples, undertaken site survey to develop a delivery and installation plan, and have secured a highly favourable discount and service package.

The cross-institution partnership makes a clear commitment to build complementary strengths in bioscience, biomedicine, and biotechnology; to attract researchers and resources to the North East; and to place the institutions at the forefront of structural biology. As endorsement of this commitment, the three institutions have committed to provide matched contribution totalling 30% of the equipment cost, as joint capital investment.