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Epithelial-mesenchymal crosstalk in the pathology of influenza virus infection

Project description

Profiling the role of fibroblasts in influenza virus infection

Influenza virus infects the airway epithelium, triggering irreversible progression of chronic obstructive pulmonary disease (COPD). However, the mechanisms are not fully known. Fibroblasts produce the extracellular matrix (ECM) of the connective tissue beneath the airway epithelium. Fibroblast activation and excessive deposition of ECM are likely the key drivers of COPD progression. With the support of the Marie Skłodowska-Curie Actions programme, the EMC-FLU project will leverage an advanced co-culture model consisting of patient-derived airway epithelial cells and human lung fibroblasts. It will unravel the crosstalk between the airway epithelium and fibroblasts, and find a potential drug target that could prevent the progression of COPD.

Objective

Influenza virus infects the airway epithelium. The connective tissue underneath the epithelium consists of extracellular matrix (ECM) produced mainly by fibroblasts. Small airway fibrosis, characterized by fibroblast activation and excessive deposition of ECM, is emerging as the key driver of the progression of chronic obstructive pulmonary disease (COPD), a very common and life-threatening lung disease for which no cure exists. Irreversible progression of COPD is often triggered by influenza virus infection. However, causative mechanisms between influenza virus infection and small airway fibrosis have not been explored. In this project, the fellow will infect an advanced co-culture model of patient-derived airway epithelial cells and fibroblasts from the human lung to mimic the microenvironment of the airway. Cellular and molecular profiling of the fibroblasts will be performed by an unbiased approach using integrated and interdisciplinary methods. Especially, a unique mass spectrometry and bioinformatics workflow for deep molecular profiling of the ECM will be combined with state-of-the art single cell RNA-sequence analysis to discover profibrotic readouts. Then, she will use cells from COPD patients to translate the findings to the clinic. Finally, she will establish a host-gene specific knockdown co-culture model to elucidate the role of a specific protein that interacts with the ECM and assess the druggability of this potential target. The fellow is a pathologist from Japan with extensive experience in infection with animal models. Her expertise and knowledge in disease pathology will be integrated with the host's prestigious scientific environment. Establishment of international connections will facilitate her to become an academic leader with a unique and multidisciplinary profile to combat infectious diseases of the lung.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

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

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Call for proposal

(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Net EU contribution
€ 189 687,36
Address
INGOLSTADTER LANDSTRASSE 1
85764 Neuherberg
Germany
Region
Bayern Oberbayern München, Landkreis
Activity type
Research Organisations
Links
Total cost
No data