Developing a lung organoid signalome for real-time analysis of senescence-associated cellular cross talk

Why did we fund this project

This award aims to develop an in vitro system for real time visualisation of senescence-associated cell signalling in the lung to replace some mouse models of ageing.

Repeated exposure to inhaled agents including tobacco smoke, allergens and pollution damages the lungs over time. Accumulated damage and ageing reduce the ability of cells to respond to challenges, until they become senescent. Senescent cells are unable to divide, repair themselves or die. They induce neighbouring cells to become senescent and their accumulation is linked to diseases of ageing, including chronic lung disease. Research in this area predominantly uses transgenic mice and involves procedures to induce lung injury such as smoke inhalation. Dr Alison John aims to replace these animal models with a “signalome” of 3D lung organoids containing multiple cell types which are individually fluorescently barcoded. The signalome cell signalling can be visualised in real time to investigate the pathways which lead to senescence, how senescent cells alter neighbouring cells and induce pathological changes which lead to disease. This research could help to identify novel targets for senotherapeutic drugs to treat age-related diseases.

This award was made as part of the BBSRC/NC3Rs joint call for the development of next generation non-animal technologies (NATs).