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Infectious respiratory diseases pose serious threats to human and animal health due to their high mortality and morbidity rates. Lung structure and composition varies between species. However, large animal models, particularly ruminants, are especially useful models for studying host-pathogen interactions and the pathophysiology of both animal and human diseases(1).
Microfluidic organoid or ‘organs-on-a-chip’ platforms are a promising new group of micro-engineered models that recapitulate 3D tissue structure and physiology(2). Precision-cut lung slices are another widely used ex vivo model for visualizing the relationship between lung structure and function(3). A particular strength of 3D cell culture techniques is that they provide highly tractable experimental platforms. However, significant limitations of currently available systems include cell differentiation and their short lifespan in ex vivo culture.
The proposed research project aims to develop and optimize a functional, stable and reproducible 3D bovine cell culture model of the lung to study respiratory infectious diseases. Specifically, the student will develop and compare two different 3D culture systems for the future purpose of studying epithelial-immune cell interactions in response to infection: organoids employing a novel Organ-on-Chip technology and precision-cut lung slices using fresh tissue obtained from the Vet School’s post-mortem facility and on-site abattoir.
Both 3D culture systems will be monitored for 30 days using a range of lab techniques to evaluate cell maturation, differentiation, function and survival, including the development and/or maintenance of key innate immune system components. Finally cultures will be tested establishing an in vitro infection.
This project will be based in Bristol Veterinary School.
Please contact [Email Address Removed] for further details on how to apply.
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