An Airway-On-Chip model to investigate age-dependent epithelial-derived immunity following respiratory infection in humans
Supervisors:
Caroline Weight, Biomedical and Life Sciences, Lancaster University
Alexandre Benedetto, Biomedical and Life Sciences, Lancaster University
Ultan Power, Wellcome Wolfson Institute for Experimental Medicine
Summary:
The epithelium maintains a healthy breathing milieu, clearing pollutants and pathogens. In younger (<5yrs) and older (>65yrs) individuals, respectively, immature immunity and chronic inflammation impair its function, increasing susceptibility to infections. Current in vivo and in vitro models of respiratory infection are either impractical or lacking, to gain a complete understanding of airway bacterial and viral infections. To develop a powerful, convenient, and versatile study model, this project will exploit Airway-On-Chip (AoC) technology that recapitulates the mechanics of human breathing on a microchip.
Nose epithelium derived from people of different ages will be grown in this system and exposed to a common bacterial pathogen (Streptococcus pneumoniae) that kills over a million older adults and young children a year, often associated with respiratory syncytial virus (RSV) infection. These AoC cultures will be infected with S. pneumoniae and/or RSV to study host-pathogen-pathogen interactions and identify susceptibility mechanisms by comparing AoCs derived from susceptible (<5yrs, >65yrs) vs healthy (18-65yrs) people.
This investigation will involve primary cell-culture, microbiology, biochemistry, immunocytology, on-chip fluorescence microscopy, and image analysis techniques, as well as microfabrication/microfluidics and bioinformatics, thus providing diverse technical training in advanced biomedical technologies.