MRC Respiratory Development and Disease Consortium Dr Matt Hind and Dr Charlotte Dean National Heart and Lung Institute, Imperial College and MRC Harwell

Background Respiratory disease is common and increasing in prevalence WHO predicts COPD rise from 5th to 3rd commonest cause of death by 2020 COPD costs NHS in excess of £1bn annually Lung cancer common, highest mortality Mismatch between funding available and prevalence of disease Few effective treatments for chronic respiratory disease

Consortium members National Consortium across UK (IC, UCL, Cambridge, Southampton, Nottingham, Newcastle and Sheffield (28 PIs) International expertise in mouse lung phenotyping and disease modelling Strong link between bench and clinic

Translational pipeline Mutant studies Disease Modelling Human tissue studies (primary cell culture, tissue modelling and ex vivo models) with mission of first into man studies Link with existing NIHR funded Respiratory BRU and BRC’s with mission of first into man studies

Strategic aims To prioritize target genes identified from investigator led research Secondary phenotyping of selected mutants eg asthma; flexivent lung function, immunological profiling, epithelial barrier integrity gene function from development through to adulthood and the role in established disease models develop high throughput phenotype screening (WBP)

Research Aims models of bronchopulmonary dysplasia or prematurity models of asthma models of COPD/emphysema models of lung cancer models of acute lung injury models of fibrosis models of lung regeneration

Plan of action Investigator led phenotyping tailored to research interest but overlap between groups and outside consortium both airway and parenchymal specific cre drivers use of conditional and inducable conditional tissue (CCSP-cre, SPC-cre) specific and other suitable drivers eg myeloid specific To maintain MRC lung database for consortium members to upload info

Delivery of strategic aims Prority of initial genes where facilities (funding and space) exists to take mice currently Selection of candidate genes based on consensus and equity across disease areas Provision of mutants Feedback of metrics

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