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Development of an Advanced Airway-On-A-Chip Model to Investigate Neuronal Hypersensitivity in Chronic Cough

Project description

New airway-on-a-chip model to decode chronic cough

Currently, there are only limited treatment options for people suffering from chronic cough. The ERC-funded REVEAL project thus aims to develop an airway-on-a-chip mimicking human biology more accurately than animal models. By integrating primary human cells and stem cell-derived neurons, researchers will recreate the respiratory tract including the intricate innervation and immune cells. With this approach, the scientists investigate how neuronal hypersensitivity triggers persistent coughing, providing a platform for personalised treatments and more effective drug screening. The tool could also revolutionise research in conditions such as asthma and obstructive pulmonary disease. Ultimately, this approach will support ethical research standards by reducing reliance on animal testing while accelerating the discovery of successful therapies.

Objective

Coughing is one of the most frequent reasons for physician appointments, and chronic coughing affects one in every 10 people in Europe. It has severe consequences on the patients’ quality of life. Treatment options are limited. Because animal models do not accurately replicate the human disease, the underlying mechanisms that trigger the onset of chronic coughing remain unclear and several promising drug candidates have failed in clinical testing. Human in vitro models could overcome these hurdles if all relevant cell types are integrated. In the REVEAL project, we will develop a comprehensive airway in vitro model to gain insight into the mechanisms underlying the onset and manifestation of neuronal hypersensitivity in chronic cough. We will develop a novel airway-on-a-chip that replicates the complex architecture of human airway tissue with innervation, immunocompetence, differentiated epithelium, and perfusable vascularization using primary cells and iPSC-derived neurons. The novel chip will facilitate high-throughput experiments. Disease models will be created using cells from chronic cough patients followed by the induction of inflammation. We will investigate neuroimmune interactions that trigger neuronal hypersensitivity and use the chip for drug screening. The REVEAL model will help to reduce the burden of chronic cough by offering a better understanding of neuronal hypersensitivity in the airways. It will facilitate the development and testing of new drugs, offer a tool for personalized medicine, and provide a new approach methodology for risk assessment and toxicity testing. This will support the 3R principles, replacing and reducing animal testing in basic and applied research. The anticipated outcome of this project will also have an impact on other highly prevalent chronic airway diseases by providing a platform technology to study conditions such as asthma and chronic obstructive pulmonary disease (COPD), achieving a positive impact for many patients.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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Host institution

UNIVERSITAETSKLINIKUM AACHEN
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.

€ 1 498 775,00
Address
Pauwelsstrasse 30
52074 Aachen
Germany

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Region
Nordrhein-Westfalen Köln Städteregion Aachen
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 1 498 775,00

Beneficiaries (1)

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