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Developing a new model of the human air-blood barrier to study immune cell translocation and to test new therapies against viral lung infection
Supervisors: Dr Claire Smith and Professor Rosalind Smyth
We are looking for a PhD student to join the group of Dr Claire Smith. The post-holder will work on a project funded by a grant from Animal Free Research UK which brings together world-leaders in the fields of respiratory virology and cell biology. This project will develop a 3D human air-blood barrier model to closely mimic the influx of immune cells into the infant lung during respiratory virus infection.
To do this we will grow lung epithelial cells, in combination with an endothelial cell layer, and will reproduce the blood microcirculation using a microfluidic system. The movement of immune cells (neutrophils) across the endothelial-epithelial cell barrier will be quantified using time-lapse fluorescence microscopy, similar to intravital microscopy in animals.
We will study the host immune response at the single-cell and population level using flow cytometry (to measure cellular markers) and RNAseq to examine the immune cell signalling pathways. This will help us identify baseline measurements of our model and also possible novel host factors that support viral clearance and minimise airway damage and inflammation. The result of our experiments, where we test new RSV drugs in our model, will not only support the replacement of animals for human anti-viral testing, but also will further our understanding of this condition in this important area of drug discovery.
References:
1. Deng Y, Herbert JA, Robinson E, Ren, L, Smyth RL. Smith CM. Neutrophil: Airway Epithelial Interactions Result in Increased Epithelial Damage and Viral Clearance during RSV Infection. Journal of Virology (2020)
2. Herbert JA, Deng Y, Hardelid P, Robinson E, Ren, L, Moulding D, Smyth RL. Smith CM. β2 integrin LFA1 mediates airway damage following neutrophil trans-epithelial migration during RSV infection. European Respiratory Journal. (2020); doi:10.1183/13993003.02216-2019
3. Deng Y, Herbert JA, Smith CM, Smyth RL. An in vitro transepithelial migration assay to evaluate the role of neutrophils in Respiratory Syncytial Virus (RSV) induced epithelial damage. Nature Scientific Reports (2018), volume 8, Article number: 6777 DOI: 10.1038/s41598-018-25167-4