Technologies for an in-vitro carbon copy of lung disease

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Our proposed work focuses on the lung, addressing physical aspects of how it maintains a physiological balance of mucus production and clearance, which is the first barrier to any airborne infection. Chronic lung disease can lead to development of a common condition known as chronic obstructive pulmonary disease (COPD) and, as reported widely in 2020, can result from the severe inflammatory processes triggered as the body responds to viruses such as SARS-Cov-2. There are also a number of prevalent genetic conditions that affect the lung. Cystic Fibrosis (CF), for example, manifests fundamentally as problem of impaired muco-ciliary clearance with patients developing airway obstruction, chronic infection, and subsequent inflammatory lung damage. Ciliopathies are genetic conditions that affect the motile cilia organelles themselves. In all these diseases, there is interplay between the specific cause of disease, and the health and function of the lung organ more broadly, and there is extremely large and poorly understood patient-to-patient variability. Clinical practice could be vastly more effective if there was a way to promptly and reliably create a model system that represented the particular patient, with their state of disease, and on which to rapidly test therapies. This means using the patient's primary cells from lungs, their resident macrophages, and any other relevant infection/co-infection/microbiota. A high fidelity disease model can then be built, together with scaffolds that can represent the extracellular matrix of interest, and any vasculature and geometric/structural boundaries. It is clearly time for life-sciences to move on from studying pathogens, hosts, stem cells, etc. each in isolation from each other. What we propose here are a series of technological steps in the direction of being able to rapidly and reliably, and without intensive labour, create a carbon copy of a certain organ (we will focus on lung) at the moment of serious disease, for the purpose of optimising treatment. This dovetails very well with increasing common pipelines of sequencing, with high throughput facilities in some hospital able to sequence samples down to single cell resolution. Our carbon copy platforms will recreate the relevant organ phenotypes, and enable physiological and physical readouts as well as molecular. We pay particular attention to the sustainability (scale and cost) of the technologies that we will propose to develop.