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Unveiling lung resilience mechanisms: a ground-breaking way to cope with air pollution

Project description

Lung resilience mechanisms in particularly polluted environments

Air pollution, intensified by heatwaves and wildfires, primarily affects the lungs, sometimes causing life-threatening damage that is resistant to standard treatments. The ERC-funded KINTSUGI project will explore the body’s natural lung resilience to better understand how respiratory health is maintained. Focusing on human adaptation to particulate pollution and resilience seen in smokers, the project will examine the role of the airway submucosal gland (SMG), essential for mucus secretion and antimicrobial defence. Researchers will analyse clinical samples and develop 3D in vitro models to study lung responses to pollutants. Mathematical modelling will further explore the complex interactions within the SMG, aiming to reveal how the lungs withstand environmental stressors and maintain function.

Objective

"Air pollution, exacerbated by heatwaves and wildfires, affects primarily the lungs, leading to potentially life-threatening effects eluding conventional treatments. In response, KINTSUGI adopts a new perspective by exploring lung resilience mechanisms, to understand how respiratory health is maintained in most individuals: drawing on evidence from both a broad evolutionary standpoint, where humans have evolved in environments exposed to particles and proofs of lung resilience observed particularly in smokers, it seeks to redefine the paradigm of investigating lung response to particulate pollution.
For that, KINTSUGI focuses on the airway submucosal gland (SMG), an ectodermal appendage lining the airways, renowned for its unique properties in mucus secretion, antimicrobial activity and a potential niche for proximal airway stem cells. The hypothesis posits the airway SMG as a crucial signalling hub, orchestrating responses to external perturbations to ensure proximal lung resilience. Using dissected clinical samples of SMG, it aims to unravel cell interactions intricacies within this niche, ultimately generating a ""SMG-related resilience signature"". Additionally, 3D in vitro models replicating the in vivo architecture and function of airway SMGs will be established for the study of mucociliary clearance, antimicrobial activity, and regeneration studies under both homeostatic conditions and particles exposure. KINTSUGI further integrates probabilistic mathematical modelling, considering microscopic interaction rules within the SMG, to elucidate macroscopic behaviours underlying lung resilience at different time scales.
KINTSUGI anticipates impacting broader scientific communities, as such health, biology, and evolution, by uncovering fundamental insights into the mechanisms governing resilience. The impact on health and its potential to resonate across diverse scientific disciplines positions KINTSUGI as a ground-breaking initiative with far-reaching implications."

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2024-COG

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Host institution

UNIVERSITE DE BORDEAUX
Net EU contribution
€ 1 978 475,00
Address
PLACE PEY BERLAND 35
33000 Bordeaux
France
Region
Nouvelle-Aquitaine Aquitaine Gironde
Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 1 999 905,00

Beneficiaries (2)