Cryogenic single-particle electron microscopy (Cryo-EM) has become the method of choice for determining the structures of large macromolecular complexes and membrane proteins – targets that have been challenging for X-ray crystallography. Exciting recent advances in cryo-EM now allow for structure determination at high resolution, of proteins in multiple states, of smaller proteins and of membrane proteins within a natural lipid environment. In this BAG, we will use the state-of-the-art cryo-EM facility at the ESRF to determine the structures of intricate protein machineries including large multi-subunit complexes, protein-nucleic acid complexes and membrane protein complexes. Our projects will contribute to a better understanding of essential cellular processes such as energy conversion and cellular respiration, nitrate and ammonium metabolism, ribosome and ribosome-associated functions, and DNA damage repair and maintenance mechanisms.