Mechanisms of steroid-resistant airways inflammation in asthma

Project Overview

A major immunological mechanism driving ‘Type 2 high’ asthma is the local production of type 2 cytokines acting on the airway epithelium to produce factors such as eotaxin to recruit eosinophils to the airways. Whilst many asthmatics respond well to inhaled corticosteroids, a significant proportion have inflammation which is resistant to steroids. The mechanism underlying this process is unknown, and better understanding of this pathway could lead to identification of novel drug targets for a disease which affects 350 million people worldwide.

We use in vitro culture of primary human airway epithelial cells obtained at bronchoscopy as well as nasal polyps and cell lines to investigate the airway epithelium. The primary aim of this project is to dissect the mechanisms of steroid resistance in response to bacterial infection, TLR agonists and alarmins by measuring IL-13-induced eotaxin release from these cells and RNA sequencing of the epithelial transcriptome. These studies will be supplemented by ex vivo analysis of bronchial epithelial samples from well-characterised asthmatics with steroid-responsive or steroid-resistant disease and by ex vivo analysis of ccsp/IL-13 bi-transgenic mice.

Training Opportunities

The Respiratory Medicine Unit laboratory is located at the John Radcliffe Hospital where we have resources and facilities to undertake cellular and molecular immunology techniques.  The skills utilised will be tissue culture, ELISA cytokine assay, multi-parameter flow cytometry, multiplex assays and RNA sequencing.  We have the ability to utilise proteomic techniques in collaboration with the Target Discovery Institute.   This project would enable students to do basic science experimental techniques as well as get involved with clinical research.  

Theme

Immunology & Infectious Disease

Admissions

Project reference number: 935

Funding and admissions information

Supervisors

Name Department Institution Country Email
Dr Timothy Hinks MRCP Experimental Medicine Division Oxford University, John Radcliffe Hospital GBR timothy.hinks@ndm.ox.ac.uk
Professor Ian Pavord FMedSci FRCP Experimental Medicine Division Oxford University, John Radcliffe Hospital GBR ian.pavord@ndm.ox.ac.uk

There are no publications listed for this DPhil project.