Targeting, Localisation and Identification in Cryo-ET

One of the main benefits of cryo-electron tomography (ET) is direct visualisation of the sample itself, without the need for stains or fixation. A consequence of this direct imaging is that every molecule in the sample contributes to the resulting tomogram, and for complex specimens such as cells or viruses, it can be challenging to identify a specific feature of interest. This chapter discusses two approaches to help guide collection and interpretation of data from cryo-ET: correlative light and electron microscopy (CLEM) and molecular tagging. These methods can be used independently or together and help cryo-ET practitioners identify areas for data collection and localise or identify specific molecules in their reconstructed tomograms.