A cryo-electron microscope for structural biology, including single-particle and tomography, at KCL.

The characterization of biomolecules, and proteins in particular, at the molecular level, is critical for the fundamental understanding of biological processes, as well as for new drug development. In particular, the capacity to determine the atomic details of how such proteins interact (between proteins, but also with DNA, lipids, sugars, drugs etc.), or how their architecture changes during their activity, is essential to decipher their function.
In recent years, Electron microscopy has become the main method to obtain such molecular information, as highlighted by the 2017 Nobel prize in Chemistry to the pioneers of the methodology.
We seek to acquire such an electron microscope, which will permit KCL to gain the capacity to make use of this emerging technology. This instrument will permit us to not only to develop our existing research at KCL, but will also be instrumental to develop new avenues of research, and for the training of the next generation of biomolecular scientists. In addition, a central aspect of the instrument we seek to purchase, is that it allows not only to gain molecular details of proteins in isolation, but also to observe them in the context of their biological function. This will permit us to bridge our studies across scales, from molecules to cells. In particular, we will use this equipment extensively in our research efforts to understand proteins involved in bacterial virulence and antibiotic resistance, viral pathogenesis (including SARS-CoV-2), cancer and tumour pathogenesis, and cardiovascular diseases.

Since the emergence of the Direct Electron Detector technology, cryo-Electron Microscopy (cryo-EM) has undergone a "resolution revolution", and is rapidly becoming the main method for protein structure determination. As part of the LonCEM consortium, we have access to a state-of-the-art microscope, dedicated to high-resolution, high-throughput data collection. We however lack an in-house instrument, that permits us to screen and optimize conditions for cryo-EM analysis, and for intermediate-resolution structure determination. The aim of this application is to obtain the funding for a 200kV TEM microscope, with autoloader and Direct electron detector, and capable to Tomography applications. This instrument will not only be a feeder microscope for the aforementioned LonCEM facility, but will also be employed for in-house data collection, for preliminary characterization of samples and/or for applications where high-resolution is not critical. This will allow us to massively broaden the access for this technology, by increasing our capacity for training of new users, and by providing access to non-expert users who will be able to use this instrument to address a wide range of questions, from basic science to drug development. In addition, this instrument will form a critical bridge to existing facilities to observe cells and tissue by electron microscopy, and to use cryo-electron tomography to determine protein structures in-situ.