Understanding the immunoepigenetics of asthma

Asthma is the world’s most common chronic lung disease. It is increasing rapidly in incidence, but it is not known why. It arises from the complex interplay of genetic predispositions and the influence of environmental factors early in life, particularly early life infections with bacteria like haemophilus influenzae and with viruses like respiratory syncytial virus (RSV), and this points strongly to epigenetic changes being induced in the airway epithelium. 

It has been previously hard to decipher these mechanisms, but that is now becoming possible due to the ability to obtain direct airway samples at bronchoscopy and via nasal brushings and importantly the advent of technologies allowing analysis of epigenetics on small tissue samples and even at a single cell level.

We have generated large epigenetic and immunological datasets of airway epithelium and bronchial biopsies at single cell resolution. We also have DNA methylation data from a large paediatric cohort with early life RSV. We have developed a murine model of long-term infection with haemophilus influenzae and so, for the first time, can model the interactions and consequences of early life bacterial / viral coinfection.

We aim to exploit these datasets and models to understand in detail the specific immunoepigenetic changes in asthma and early life infection in mice and humans with a view to developing targeted epigenetic therapies.