Most diseases are caused by proteins that do not function correctly. With electron cryo-microscopy, the three-dimensional structure of interacting proteins can be determined at near-atomic resolution. This precise atomic arrangement is crucial to understand how a protein functions or dysfunctions, but for electron cryo-microscopy, the protein needs to be contained precisely in a very thin slice that is cut out of the cell. Finding the relevant proteins within the cell is like finding a needle in a haystack. The research team will build a novel microscope in which a target protein (the needle) lights up after which the rest of the cell (the haystack) can be effectively trimmed away. The resulting slice containing the target protein(s) can then be transferred to a high-resolution cryo-electron microscope.