Cryo Electron Tomography (CryoET) is used to resolve biomolecules within their cellular environment down to an unprecedented resolution below 1 nm. In this way, individual proteins can be recognized by their shape alone, without any labelling. Even different conformations can be distinguished, opening a window to truly understanding molecular sociology.
By opening up new approaches to understanding spatial protein structures and interactions, CryoET imaging helps to decode cellular mechanisms and translate these insights. For example, they may help to find effective treatments for many diseases.
But imaging at subnanometer resolution comes with major challenges: it is cost intensive, has a high training effort, involves many instruments steps and mostly the structures of interest cannot be selectively visualized in the electron microscope (EM). To secure a high success rate, the target volume for the EM imaging therefore needs to be identified and located with the highest possible resolution during the light microscopy (