Project description
Tissue imaging platform to protect aortic valve
Calcifying aortic valve disease (CAVD) alters the extracellular matrix of the aortic valve, leading to severe heart dysfunction. The molecular mechanisms behind this disease remain unclear and currently no drug therapies are available. Valve replacement is the only treatment option. The ERC-funded REVALVE project aims to address this knowledge gap and enhance imaging of biological matrix formation processes, ranging from the micron to nanometer scale, by creating a tissue imaging platform for CAVD. It will develop a human CAVD-on-a-chip that mimics the early stages of CAVD using mechanical and biochemical cues. It will also implement the collection of cryo-sections of the extracellular matrix, enabling their transfer to a transmission electron microscope for further analysis.
Objective
Calcifying Aortic Valve Disease (CAVD) is a cellular-driven disease that actively alters the structure and composition of the valve extracellular matrix, leading to severe disfunction of the heart. Because the molecular mechanisms underlying CAVD are still unknown, there are currently no drug-based therapies and valve replacement is the only available treatment.
Specifically, it is still unknown (1) how the disease modifies the extracellular matrix (ECM) to become susceptible for mineralization, (2) how cell differentiation and matrix modification lead to calcification, and (3) how the mineral develops within the matrix. We lack these answers mainly due to our inability to characterize matrix development with the required chemical and structural details during the CAVD process.
I aim to push our capability for in situ imaging of ongoing biological matrix formation processes from the micron to the nanometer scale by creating a designer tissue imaging platform for CAVD. This will be achieved by:
• creating a human CAVD-on-a-chip that allows the application of mechanical and (bio)chemical cues to accurately emulate the early stages of CAVD;
• designing the chip to accommodate a 3D correlative multiscale imaging and spectroscopy workflow to study matrix modification and mineralization in the native state from the micrometer to the nanometer scale;
• developing a method to (1) collect cryo-sections from the ECM created at precisely selected points in space and time, to (2) transfer these to a transmission electron microscope and (3) revive -inside the microscope- the biological processes that are ongoing in the at the moment of cryo-arrest. This will allow for the first-ever dynamic nanoscale imaging of ongoing ECM processes.
These new capabilities will allow breakthroughs in understanding the role of matrix interactions in aortic calcification, opening the way for future development of drug-based treatments for CAVD.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences physical sciences optics microscopy
- natural sciences physical sciences optics spectroscopy
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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Call for proposal
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(opens in new window) ERC-2023-ADG
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6525 GA NIJMEGEN
Netherlands
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