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Multiscale mechanobiological synergies in vascular homeostasis, ageing and rejuvenation

Project description

Multiscale digital twins support development of a vascular rejuvenation paradigm

The European aging population is growing, and aging is the most important risk factor for atherosclerosis. Also called hardening of the arteries, the condition’s build-up of fatty materials or plaques causes hardening and narrowing of vessels. Current treatments including drugs and stents are palliative. The ERC-funded JuvenTwin project aims to develop an unprecedented vascular rejuvenation paradigm based on small molecule inhibitors and cell mechanical stimulations. To simulate and screen rejuvenation treatments, JuvenTwin will leverage multiscale digital twins. These will integrate a 4D high-resolution strain mapper and a micromechanical computational model simulating the dynamical interactions of 100 000 vascular cells in patient-specific arteries.

Objective

Whilst 30% of EU citizens will be over 65 and 10% over 80 by 2050, the healthspan accounts for only 80% of the total life expectancy according to Eurostat, due to the high prevalence of disabling diseases related to the age-induced arterial stiffening. The current paradigm in medicine is to palliate these diseases with sophisticated devices. In JuvenTwin, I propose a complete shift of paradigm by combatting the mechanobiological effects of vascular ageing. Vascular rejuvenation faces many challenges that have only been explored by molecular biologists. My ambition is to address these challenges with a high-risk approach relying on multiscale digital twins and enabling to simulate and screen effective rejuvenation treatments. My hypothesis, already supported by preliminary results, is that this can be achieved by doping the synergistic effects of mechano-regulation in human arteries, which are gradually compromised with vascular ageing. JuvenTwin’s four specific objectives are: 1/ Decipher how ageing affects cell phenotypes and the signalling pathways of mechano-regulation, 2/ Assess the effects of ageing on the mechanical interactions between cells and their matrix, 3/ Simulate computationally the multiscale synergies participating to patient-specific vascular mechano-regulation and finally 4/ Take the control of mechanobiology in aged arteries using small molecule inhibitors and cell mechanical stimulations. With my team, we will reach these objectives by developing two completely novel methodologies: a 4D high-resolution strain mapper and a micromechanical computational model simulating the dynamical interactions of 100,000 vascular cells in patient-specific arteries. Our interdisciplinary approach combining digital spatial transcriptomics, laser interferometry and neural networks will be of very high-gain for discovering therapies against the adverse mechanobiological effects of vascular ageing, potentially reaching the pre-clinical stage at the horizon 2030.

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Topic(s)

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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-2023-ADG

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Host institution

INSTITUT MINES-TELECOM
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.

€ 2 435 688,00
Address
19 PLACE MARGUERITE PEREY
91120 Palaiseau
France

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Region
Ile-de-France Ile-de-France Essonne
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.

€ 2 435 688,00

Beneficiaries (2)

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