Enhancing the cryo-electron microscopy capacity at Imperial College London for single particle and tomographic studies.

Electron microscopy (EM), especially cryo-EM single particle analysis technique, has become increasingly powerful in studying large macromolecular machines, due to the development in providing increasingly higher resolution structural information of large transient macromolecular complexes including the capability of capturing multiple functional states. The realization that many important macromolecular complexes are transient and intrinsically dynamic makes them not amenable to study by well-e stablished structural biology techniques such as X-ray crystallography. Cryo-EM, on the other hand, requires relatively small amount of samples and can capture transient and distinct functional and conformational states. With the development of algorithms that deal with heterogeneous populations within samples, cryo-EM single particle analysis becomes the ideal method for studying the complex dynamics of many key macromolecular machines. Furthermore, the ability to image organelles and sections of a cell at high resolution will enable the investigations of individual macromolecular complexes to be placed in a cellular environment, thus bridging structural molecular biology with cell biology and physiology. To achieve this, we need a modern high resolution and high sensitivity electron microscope that is capable of obtaining high quality data in an automated fashion.