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Immune-mediated control of epithelial integrity: Does the immune response to influenza infection cause long-term changes in lung function?

Project Description

Surviving influenza infection requires a careful balance between factors that promote immunity and eradicate the virus and factors that limit the immune response and minimise damage to the lung epithelium. One mechanism to limit damage is to drive an active process of epithelial repair and regeneration, essential to maintain barrier integrity in the lung and to enable gas exchange to continue. Evidence suggests that repaired epithelium is different to the original, and these changes may contribute to multiple pulmonary disorders including secondary infections, increased sensitisation to allergens, and long-term fibrosis. Our aim in this study is to investigate the role of regulatory cytokines in directing the process, and the long-term consequences, of epithelial repair during influenza infection.

The project will use in vitro and in vivo approaches involving both human cell culture and mouse models of infection. Our first aim is to determine how influenza infection affects the proliferation, activation and function of epithelial precursors in the lung, and for this we will use a murine infection model with Influenza A/PR8 virus, and a human cell culture of isolated precursors. Our second aim is to determine which cytokines regulate the proliferation and differentiation of epithelial cells during and after influenza infection, and whether different cytokines leave distinct footprints in the quality of the repaired lung epithelium. Our third aim is to identify the cell-cell interactions that direct the process of lung repair and lung alteration during influenza infection, asking whether cytokines act directly on epithelial cells or whether cooperation between different immune cells is involved.

A PhD candidate on this project is expected to become experienced in
o Mucosal and cellular immunology
o Respiratory airway biology
o Flow cytometry
o Animal handling and the use of transgenic mice, including cytokine-reporter strains
o In vivo models of influenza infection
o Cell culture and the in vitro differentiation of airway epithelial cells
o Transcriptomic analysis and large data interpretation

This project will be supervised by Dr Georgia Perona-Wright (Immunologist, University of Glasgow) and Dr Linda Yrlid (Immunologist and Epithelial Biologist, Astrazeneca). The student will be primarily based in Glasgow with regular visits to Astrazeneca (Gothenburg).

Please note, although the application system will request a research proposal, this is NOT required for this application.

Funding Notes

The studentship is funded by a BBSRC Collaborative Training Partnership (CTP) Award held between the university of Glasgow and Astrazeneca.

Full UK/EU tuition fees

Doctoral stipend matching UK Research Council National Minimum
Additional funding is available over the course of the programme and will cover costs such as research consumables and training.
Applicants should possess a minimum of an upper second class Honours degree, Master's degree or equivalent, in a relevant subject.
Applicants whose first language is not English are normally expected to meet the minimum University requirements (e.g. 6.5 IELTS)

How good is research at University of Glasgow in Clinical Medicine?

FTE Category A staff submitted: 177.40

Research output data provided by the Research Excellence Framework (REF)

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