Monocyte to Macrophage Trajectories After Lung Injury Spatio temporal investiga...
Monocyte to Macrophage Trajectories After Lung Injury Spatio temporal investigation molecular regulation functional implications for lung regeneration and immunity
The lung is particularly exposed to airborne and blood-borne insults. The mechanisms underlying lung tissue repair are therefore of fundamental biological importance and have critical implications for the prevention life-threateni...
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31/12/2029
ULIEGE
2M€
Presupuesto del proyecto: 2M€
Líder del proyecto
UNIVERSITE DE LIEGE
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Fecha límite participación
Sin fecha límite de participación.
Financiación
concedida
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el día 2024-06-20
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Información proyecto MoMacTrajectALI
Duración del proyecto: 66 meses
Fecha Inicio: 2024-06-20
Fecha Fin: 2029-12-31
Líder del proyecto
UNIVERSITE DE LIEGE
No se ha especificado una descripción o un objeto social para esta compañía.
TRL
4-5
Presupuesto del proyecto
2M€
Fecha límite de participación
Sin fecha límite de participación.
Descripción del proyecto
The lung is particularly exposed to airborne and blood-borne insults. The mechanisms underlying lung tissue repair are therefore of fundamental biological importance and have critical implications for the prevention life-threatening inflammatory and tissue-damaging responses. Lung-resident tissue macrophages and inflammatory monocyte-derived macrophages (InfMoMac) are key players in the maintenance of homeostasis, repair responses and disease pathogenesis. Yet, to date, the complexity of lung macrophage responses after injury is far from being resolved. Here, we propose to explore InfMoMac trajectories and functional diversity in an unprecedented manner. To this end, we will use mouse models of infectious and non-infectious lung injury combined with single cell and spatial analyses, robust fate-mapping models and gene targeting approaches to investigate the spatio-temporal regulation, the subtissular niches, the intrinsic molecular programs and the extrinsic stress-, inflammation- and niche-related signals imprinting the identities and functions of InfMoMac subpopulations, and the functional consequences of the maintenance of InfMoMac for lung immunity to a subsequent challenge. Finally, we will investigate the interactions of InfMoMac with niche cells in humans by analyzing the InfMoMac landscape in human injured lungs and by studying a novel human embryonic stem cell-derived lung organoid model in co-culture with monocyte-derived cells. Based on robust preliminary data, sophisticated models and cutting-edge technologies, this ambitious project will increase our understanding of the basic mechanisms underlying the fine-tuning of InfMoMac trajectories in response to lung injuries and will thus provide robust foundations to manipulate their fate in medically relevant conditions such as severe respiratory viral infections and acute respiratory distress syndrome.