Biomechanical forces and cellular responses in platyhelminths and host cells

Parasitic trematodes such as Schistosoma mansoni and Fasciola hepatica are major causative agents of neglected tropical diseases, affecting over one billion people worldwide. Despite research on their molecular biology and immunology, the role of biomechanical forces in parasite–host interactions remains poorly understood. Yet, throughout their life cycles, these parasites encounter and actively generate mechanical forces that are critical for host invasion, migration, and persistence within diverse tissue environments. This project aims to elucidate how parasite-derived mechanical cues influence host-cell behavior at molecular, structural, and functional levels. To achieve this, we will first establish physiologically relevant hydrogel-based culture systems that mimic tissue mechanics and support relevant host-cell types, including endothelial, hepatic, and biliary cells. Using these platforms, we will quantify parasite-generated forces via traction force microscopy, enabling dynamic mapping of mechanical interactions during parasite attachment. To link mechanical stimulation to cellular signaling, we will investigate mechanosensitive calcium responses, focusing on PIEZO1-dependent pathways using live-cell imaging and controlled mechanical perturbations. Finally, we will assess downstream effects on host-cell gene expression, signaling, and morphology using transwell co-culture systems and advanced worm-on-chip platforms under physiologically relevant flow conditions. By integrating biomaterial engineering, force measurements, live-cell imaging, and transcriptomic analyses, this project will provide a comprehensive mechanobiological framework for understanding parasite–host interactions.

PhD start: 12/01/2025