Parasitology meets cryo-electron tomography – exciting prospects await

Cryo-electron tomography (cryo-ET) is a cryo-electron microscopy (EM) approach that allows 3D imaging of cellular structures in near-native, frozen-hydrated conditions with molecular resolution. Continued development of technologies, including direct electron detectors, phase plates, and energy filters, has improved the information yield from cellular samples, which is further extended by newly developed workflows for data collection and analyses. Moreover, advanced sample-thinning techniques, such as cryogenic focused ion-beam (cryo-FIB) milling, provide access to parasitic events and structures that were previously inaccessible for cryo-ET. Cryo-ET has therefore become more versatile and capable of transforming our understanding of parasite biology, particularly that of apicomplexans. This review discusses cryo-ET’s implementation, its recent contributions, and how it can reveal pathogenesis mechanisms in the near future using apicomplexans as a case study.