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SYNBIO.ECM: Designer extracellular matrices to program healthy and diseased cardiac morphogenesis

Project description

A novel computer-aided design platform for cardiac tissues fills in the gaps

The billions of cells in our body rely not only on their intracellular components to carry out their myriad intricate functions but also on the extracellular matrix (ECM). The ECM provides physical scaffolding for the cells and participates to the chemical and mechanical signaling among cells to orchestrate tissue development in homeostasis and disease. Yet, despite tremendous progress in cell engineering, we continue to engineer synthetic tissues and organs by trial-and-error, without an actionable, quantitative understanding of ECM-cell interactions. The EU-funded project SYNBIO.ECM plans to fill this important gap in cardiac tissue engineering. Bottom-up experiments will inform models leading to a computer-aided design and manufacturing (CAD/M) platform for creating replicas of healthy and diseased human hearts and heart parts.

Objective

To meet medical needs worldwide, tissue engineering must move from successful pre/clinical products towards an effective process to meet Worldwide medical needs, but this is challenging since a quantitative design framework has not emerged, yet. Synthetic biology (SYNBIO) was the solution that genetic engineers found to the same problem: “Despite tremendous individual successes in genetic engineering and biotechnology […], why is the engineering of useful synthetic biological systems still an expensive, unreliable and ad hoc research process?” asked Dr. Endy in a 2005 letter to Nature. The SYNBIO solution included: i) libraries of DNA parts with well-characterized effect on cells; ii) tools to computationally design system-level assemblies, or designer-DNA; and, iii) bottom-up engineering of cell functions using progressively more complex designer-DNA. Effectively, SYNBIO introduced a computer-aided design and manufacturing (CAD/M) platform that transformed the process of engineering cells. However, since inputs from the extracellular matrix (ECM) have largely been ignored, progress towards programmable tissue-level behavior have been more modest.

Here, we will build on my experience with computational and experimental models in cardiac tissue engineering to develop a CAD/M framework for engineering cardiac tissues with computationally predictable properties, or designer-ECM. To characterize ECM-cell interactions, we will use traction force and super-resolution microscopy with fluorescence in-situ sequencing. To model multiscale ECM-cell interactions, we will use ordinary differential equations and subcellular element models. Finally, we will leverage ECM parts and human induced pluripotent stem cells to bioprint designer-ECM that recapitulate three phases of heart development: trabeculation, compaction, and maturation.

With synthetic matrix biology (SYNBIO.ECM) we will develop a CAD/M-based process and a new class of products for cardiac
tissue engineering.

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Topic(s)

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Funding Scheme

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2019-STG

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Host institution

UNIVERSITA DEGLI STUDI DI PAVIA
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.

€ 1 999 375,00
Address
STRADA NUOVA 65
27100 Pavia
Italy

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Region
Nord-Ovest Lombardia Pavia
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.

€ 1 999 375,00

Beneficiaries (1)

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