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Intrinsic and extrinsic factors controlling the development of human lung macrophages

Project description

Insight into macrophage development in the human lung

Macrophages are key immune cells that take on specialised roles in different tissues, depending on the local environment. Tissue-resident macrophages appear early during human development and influence organ growth, homeostasis and repair. Despite their importance, it is unclear how macrophages develop in the human lung and what governs their identity. With the support of the Marie Skłodowska-Curie Actions programme, the LUNGMAC project will investigate how macrophages are specified early during lung development. Researchers will employ a multidisciplinary approach to define gene regulatory networks, map macrophage distribution and identify signalling interactions. Collectively, project findings will improve our understanding of foetal lung development and tissue-specific macrophage biology.

Objective

Human tissue-macrophages demonstrate diverse functions and distinct transcriptomic profiles across organs. They are imprinted by the local tissue environment and contribute to the tissue development, homeostasis, and regeneration. The embryonic macrophages begin to infiltrate the human lung as early as seven post conception weeks (pcw). However, the mechanisms that govern lung macrophage specification and their contribution to human lung development remain poorly understood. This project aims to dissect the cell-intrinsic gene regulatory networks (GRNs), spatial distribution patterns, and signaling pathways regulating the interactions of macrophages and the human developing lung (7–22 pcw). These aims will be achieved by combining single-cell multiomic analysis, high-resolution microscopy, and signaling perturbation using novel 3D tissue models. First, this project will determine the GRNs controlling the identity of fetal lung macrophages by employing multiomic analysis tools. Second, the spatial-temporal maps of macrophages in the fetal lung will be generated using high-resolution light sheet fluorescence microscopy to investigate the distribution patterns and specific cellular niche(s). Lastly, this study will establish novel complex lung tissue models to investigate the underlying mechanisms regulating lung-macrophage interactions. These complementary techniques will expand our knowledge of human tissue macrophage specification and functions, providing insights to the field of both lung and macrophage biology.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 260 347,92
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN CAMBRIDGE
United Kingdom

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Region
East of England East Anglia Cambridgeshire CC
Activity type
Higher or Secondary Education Establishments
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Total cost

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