Glacios cryo-electron microscope for single particle analysis and electron tomography of proteins, complexes and fibrillar assemblies

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Electron microscopy has been used for decades to provide details of cell and tissue structures and to image particles that could not be seen by light microscopes, such as viruses. However, in recent years electron microscopy has undergone a "Resolution Revolution" with a combination of improvements in freezing samples (cryoEM) along with software and hardware advances. The details that can now be observed from cryoEM data include the structure of proteins to atomic resolution, the level where all atoms in the molecule can be seen. The "Resolution Revolution" has led to many new structures being determined in recent years and was acknowledged in the award of the 2017 Nobel Prize in Chemistry for these developments. Importantly, proteins that were previously too difficult to determine their atomic resolution structure are now being imaged for the first time using cryoEM data.At the University of Manchester, we have many projects supported by BBSRC funding that require access to cryoEM. However, our current microscope, the Polara, is out-dated and no longer supported by the manufacturer. Therefore, this application is to provide a state-of-the-art Glacios cryo-electron microscope to support the research of a very productive team of scientists at the University of Manchester. The Glacios cryoEM is a step-change in microscope technology which would allow us to collect data at a much faster rate, due to advances in automation, which means more images can be collected each day. The Glacios is also much more stable which will allow us to collect higher resolution images. In addition, the Glacios has compatible cryoEM sample handling with other instruments, including those in the national electron bioimaging centre, which means samples can be transferred between microscopes for data collection.The research at Manchester that needs access to a new cryoEM covers a broad range of science that is in alignment with BBSRC's strategic priorities. Projects include the analysis of extracellular matrix proteins involved in cell signalling, tissue strength and inflammation; determining the structures of membrane proteins responsible for multidrug resistance and kidney function; investigation of enzyme mechanism for biological catalysis; understanding the processes involved in synthesising proteins, and analysing virus-like particles in the development of new vaccines. These studies will benefit enormously from a new cryoEM and the University of Manchester recognises this by offering major financial support including 35% of the cost of the Glacios, plus a purpose-built room in our Electron Microscopy Facility and an expert experimental officer who will operate the microscope and train new users.