Microcrystal electron diffraction (MicroED, also known as 3D ED) and Serial Electron Crystallography emerged as promising methods for macromolecular crystal structure determination. Since the first protein structure was determined by MicroED in 2013, the method has been evolving rapidly. Several protein structures were determined and various studies show that MicroED is capable of 1) revealing atomic structures with charges, 2) solving new protein structures by molecular replacement, 3) visualising ligand binding interactions, and 4) determining membrane protein structures from microcrystals embedded in lipidic mesophases. However, cryo-EM specimen preparation of thin, undamaged and hydrated submicron-sized protein crystals remains as the main bottleneck in electron crystallography. In this project, a sample preparation protocol for electron crystallography will be developed, which includes protein crystallization, cryo-EM specimen preparation of micro-crystals, and cryo-EM screening. The student will have the opportunity to learn protein crystallization, work with cryo-TEMs, and gain experiences in multidisciplinary method development. 

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