The role of airway shear stress in pathological processes in asthma

Applications are open for a PhD scholarship at the University of Newcastle. As the successful applicant you will undertake your doctoral studies in the Priority Research Centre for Healthy Lungs at the Hunter Medical Research Institute in Newcastle. The group you will be working with is composed of a dynamic and enthusiastic combination of clinical and laboratory based scientists each of who has an outstanding research track record and exceptional facilities available to them. The team consists of A/Prof Chris Grainge, Professor Darryl Knight and Dr Nathan Bartlett.

The project will investigate the role that mechanical forces, specifically airway shear stress, plays in the development and progression of lung disease, focusing specifically on asthma. Asthma is a chronic lung disease caused by airway narrowing, resulting in symptoms of shortness of breath and wheeze. Asthmatics who have lots of symptoms due to airway narrowing suffer more from viral lung infections, which further makes their disease worse. It is known that asthmatics have impaired anti-viral innate immunity, but the mechanism underlying this is unknown.

We hypothesise that sheer stress induced mechanical forces induced at the airway epithelium during airway narrowing in asthma lead to an alteration in epithelial cell function. We wish to answer the following questions;

1. How does the respiratory epithelium react to airflow generated shear stress; does the epithelium in asthmatics respond differently to shear stress than patients with no, or different lung disease?

2. What are the mechanisms underlying the responses to shear stress in the airway. Does shear stress induce a deficit in anti-viral immunity in asthma?

3. Does shear stress alter the epigenetic status of epithelial cells in asthma or health?

This project will offer key insights into mechanisms that may play in important role in asthma. While it is now known that bronchoconstriction is actually a cause for further progression of the disease rather than a symptom alone, a key question is how exactly bronchoconstriction can lead to chronic asthma. By using samples from healthy and asthmatic donors both exposed and not exposed to shear stress, you will be able to ascertain if there is a difference in the responses of epithelial and structural cells in health and disease. Techniques will include; primary epithelial cell culture from patients with asthma and other respiratory diseases. Virus culture, propagation and genetic manipulation including potentially fluorescent tagging of virus. Biomechanical engineering including the use of computer controlled models of airway shear stresses and microfluidic experimental systems. Analysis of samples using ELISA, Western blotting, qPCR, Nano string etc.