Recent advances in cryoelectron tomography and applications to parasitology

Cryo-electron tomography (cryo-ET) has emerged as a transformative technique for visualizing the native ultrastructure of eukaryotic parasites, from proteins to cellular architecture. Recent technical advances in sample preparation, data collection, and computational analysis have enabled unprecedented insights into structural cell biology of medically important pathogens including Toxoplasma gondii, Plasmodium falciparum, Trypanosoma brucei and Trypanosoma cruzi, Cryptosporidium parvum, and Microsporidia. This review highlights the range of resolutions and cellular structures accessible by cryo-ET, and the kinds of biological insights that may be obtained, using eukaryotic parasites as case studies. Lower-resolution data (20-30 Å) provide structural information on organelles, whole-cells, and cell-cell interactions, while at the higher-resolution end, near-atomic structures can be resolved in situ using subtomogram averaging, typically for large, abundant particles such as ribosomes. Combined with orthogonal techniques, cryo-ET is a powerful tool for studying the structural cell biology of parasites.