Characterising pathogen interactions with the host at an atomic, molecular, and tissue level to tackle infection and antimicrobial resistance
This disease presents challenges in drug development due to Giardia’s unique endocytosis mechanism. Contrary to previous beliefs that Giardia lacks clathrin-coated vesicles for nutrient uptake, our high-resolution cryo-electron tomography (cryo-ET) revealed the presence of vesicles resembling those found in other eukaryotes. Further, using AlphaFold2, we identified proteins capable of forming vesicle coats, indicating a more conserved vesicular trafficking system in Giardia than previously thought. This project aims to elucidate Giardia’s endocytosis mechanism, determining the role and assembly of these vesicles and their coats. By integrating time-resolved cryo-ET, structural modelling, and CRISPR/Cas9 techniques, we plan to unlock novel therapeutic targets and strategies against Giardia, leveraging its unique endocytosis process.
Jan Kosinski (EMBL Hamburg)