Completed Cells, Biochemistry & Physiology Chemistry

An advanced cryoEM instrument for the University of Cambridge

In plain English

AI plain-English summary

A new electron microscope at the University of Cambridge will let researchers see the atomic-scale structure of large biological molecules that have resisted all other imaging methods. The problem is that many of the protein complexes central to human health—such as those involved in viral infection, DNA repair, or cell signalling—are too large or flexible to form the crystals needed for X-ray crystallography, the traditional workhorse of structural biology. Without atomic-level images of these assemblies, scientists cannot understand exactly how they work or how to design drugs that target them. The new microscope, called a cryo-electron microscope (cryo-EM), uses a beam of electrons to image flash-frozen molecules, and recent advances in detectors and software now routinely achieve sub-nanometer resolution—enough to see individual atoms in large complexes. If this facility succeeds, it will transform how Cambridge’s large structural biology community studies fundamental molecular processes. The immediate impact is on fundamental science: researchers will finally be able to map the shapes of molecules that have been invisible. Historically, such structural insights have underpinned the development of antiviral drugs, antibody therapies, and vaccines. This microscope does not itself deliver treatments, but it provides the atomic blueprints that make those treatments possible.

View original technical description
We seek support to consolidate an advanced electron cryo-microscopy (cryo-EM) facility dedicated to structural studies of biological macromolecular assemblies. The facility would provide a revolutionary new tool to the large structural biology community in the University that would enable acquisition of critical data in support of a wide and diverse range of projects tackling fundamental problems in molecular biology relevant to human health. Currently, the named applicants primarily use X-ray crystallography to study large assemblies, but many of these samples cannot be readily crystallised. The recent development of a new generation of direct electron detectors, together with sophisticated data-processing software, has dramatically improved cryo-EM analysis, which now achieves routinely sub-nanometer resolution. Until recently, researchers in the university did not have access to cryoEM, but this has changed with the recent Wellcome Trust award to purchase a cryo-EM instrument for sample screening and intermediate resolution structure determination. We are building on this support, to develop the second phase of our strategy and seek funding for an advanced microscope capable of high resolution structure determination to complement and extend our existing instrumentations.

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Researchers

Bonaventura LUISI (EPMC Awardee)

Related Research

Grants with similar aims, by meaning.

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Cryo-electron microscope for structural and cell biology
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Original classification

Cryo-Electron Microscopy Equipment grant

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