Wimberly, B. T. | Search bioRxiv

bioRxiv2022

Improved methods for the large-scale cultivation of Giardia lamblia trophozoites in the academic laboratory

The parasitic protist Giardia lamblia causes giardiasis, one of the leading diarrheal diseases worldwide. As a phylogenetically divergent eukaryote, Giardia is also an emerging model organism for exploring the diversity of core eukaryotic metabolic pathways and important molecular structures. To date, methods for the cultivation of large numbers (>109) of Giardia trophozoites have been either expensive or cumbersome, hampering structural and biochemical studies. Here, we present two improved strategies for the laboratory-scale growth of billions of adherent trophozoites, with suggestions for the optimization of media components, media preparation, and harvesting methods.

microbiology↗

bioRxiv2020

The Giardia lamblia ribosome structure reveals divergence in translation and quality control pathways

Giardia lamblia is a human pathogen of worldwide importance with limited treatment options. Its unusual molecular biology presents targets for new therapies and the opportunity to explore the fundamental features of important biological mechanisms. We determined the structure of the G. lamblia 80S ribosome by cryoelectron microscopy, revealing how it combines eukaryotic and bacterial features. The structure reveals regions that are rapidly evolving, including depletion of A and U bases from its rRNA. Specific features of the G. lamblia ribosome suggest it is less prone to stall on problematic peptide sequences, and that the organism uses altered ribosome quality control pathways compared to other eukaryotes. Examination of translation initiation factor binding sites suggests these interactions are conserved despite a divergent initiation mechanism. This work defines key new questions regarding ribosome-centric biological pathways in G. lamblia and motivates new experiments to explore potential targetable mechanisms.

molecular biology↗