Development, validation, and establishment of intestinal organoids to study host-parasite interactions in veterinary medicine

Background

At my home lab I developed an air-liquid-interface in-vitro model of the red fox (Vulpes vulpes) respiratory tract to study host-parasite interactions in canids. This model is crucial for understanding the pathogenesis and immune responses in canid lungworm infections and can be extended to study further infectious pathogens, given that foxes are reservoirs for many infective agents. Our model is used for studies on the tissue-specific response to lungworm infections using transcriptomic and proteomic approaches. The acquisition of cutting-edge intestinal organoid techniques from the host lab will open numerous avenues for future research covering broad-spectrum parasite research. This includes using intestinal organoids to understand host-specificity mechanisms and parasite-immune-interactions in gastrointestinal parasites within a veterinary and One health context. Integrating intestinal organoids from different host species will considerably enhance our current research capabilities, contribute to biobank development, and comparative studies of host-parasite interactions across various parasites, organ systems, and host species.

Aim

University of Zurich -> University of Glasgow, Scotland

I aim to acquire the necessary skills and knowledge to develop, refine, and apply intestinal organoid technology particularly for studying host-parasite interactions. This advanced in vitro-system involves three-dimensional structures derived from primary stem cells mimicking the in-vivo situation in the corresponding donor. These organoids provide a physiologically relevant model to study various aspects of host-parasite interactions as well as of gastrointestinal biology and pathology. Due to the ability of organoid systems such as intestinal organoids to closely mimic the in vivo situation and their robust and versatile nature, these approaches have emerged as a powerful tool in biomedical research and expanded in various research areas such as developmental biology, disease modelling, regenerative medicine, drug testing and technology as well as infectious disease research. Intestinal organoids are particularly valuable because of their physiological relevance, i.e. they maintain structural and functional complexity of the original in vivo environment while remaining simple enough to allow for solid inference to be drawn. Moreover, they allow for detailed studies of fundamental biological pathways and speciesspecific insights into the various biological processes relevant for a broad field of trans- and interdisciplinary research. In specific regard to my own research at my home institution, these technologies represent cutting-edge, physiologically relevant, and ethically favourable systems that are ideally suited to advance our understanding of host-parasite interaction. Acquiring the methodology of intestinal organoid development and maintenance will considerable strengthen my personal as well as our institutional portfolio and complement ongoing work.