Rickgauer, J.P. et al. eLife 6, e25648 (2017).

The ability to see where proteins are located in a cell and how they are oriented would be highly useful to biologists. Toward this goal, Rickgauer et al. report a method to determine protein location and orientation in cryo-EM images. At high resolution, an electron wave passing through a sample is imprinted with projection patterns of phase shifts that are unique to each protein and each orientation. Rickgauer et al. describe an algorithm that simulates such projection patterns for varying orientations of a given protein and then scans the cryo-EM image for targets that match the patterns. Though the method has not yet been tested in biological slices, the data highlight the potential of the approach for detecting single proteins and their orientations in the crowded environment of the cell.