Discovering the cellular landscape of the airways and the lung

Objective

Lung diseases are a leading cause of death, with increasing incidence and lack of curative interventions. The development of novel therapeutic interventions is hampered by our incomplete knowledge of the cellular complexity of the lung, as evidenced by the recent identification of the CFTR-expressing ionocyte. To overcome this limitation, we urgently need to acquire detailed knowledge of the cells of the lung, their fixed and variable molecular features, their interactions and their organization into macroscopic tissue architecture in health and disease. To achieve this, discovAIR aims to establish the first draft of the Human Lung Cell Atlas. Herein, discovAIR will combine multimodal molecular profiling of lung tissue cells with a detailed spatial mapping of the identified cell states, 3D reconstruction of lung tissue architecture, and in-depth molecular phenotyping of local cellular neighbourhoods. We will develop novel computational approaches to integrate the multilevel data of the spatial and the cellular branches of discovAIR. To identify the molecular phenotypes of cells in disease, discovAIR will include lung tissue from patients with asthma, COPD and IPF in the molecular profiling and spatial mapping effort. Moreover, discovAIR will chart cell state transitions from health to disease in a novel experimental approach, the lung cell perturbation map. The discovAIR results will be shared with the basic, translational and clinical scientific community as well as diagnostic and pharmaceutical industry through and open-access data visualization and exploration platform. For sustainability, this platform will be embedded in the Human Cell Atlas infrastructure. The discovAIR results will facilitate progress in regenerative and precision medicine and identify novel candidates for precision diagnostics and curative interventions in lung disease, thereby contributing to healthy ageing and active living in Europe.