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Probing and controlling the three-dimensional organoid mechanobiology

Objective

Interaction between cells and their mechanical microenvironment plays a key role in the regulation of development, physiology and disease. Cell behaviour is also regulated by the dimensionality of the microenvironment: 2D cultures display
biological traits that generally differ from those of 3D tissues, thus limiting their potential in biomedical research. This
limitation has been addressed by the recent development of Organoids, which faithfully preserve a number of distinctive
tissue traits. Still, current biophysical tools and conceptual frameworks are not yet suitable to probe and understand the
mechanobiology of 3D organoid systems.

This project aims to study and manipulate the mechanobiology of normal gut and colorectal cancer organoids. We will
develop tools to quantify the 3D stresses applied by an organoid embedded in a gel. By measuring its 3D surface stresses
and Young’s modulus we will quantify its interstitial pressure and contractility, key parameters in organ growth and tumour
progression.

Pressure and contractility will be related with key biological parameters such as geometry, cell adhesion and proliferation.
We will fluorescently tag proteins in the organoids that will allow us to track individual cells, as well as monitoring their
polarization and adhesion. The relationship between mechanics, geometry, and cell function will be further assessed by
chemically reducing proliferation, mechanical stresses and adhesion.

We will also modify the mechanical state of the organoids through optogenetic means. We will express proteins in the cells
to control Rho-GTPases upon illumination, thereby steering the local stresses at will. We will modify organoid pressure,
contractility and geometry and study their influence on the phenotype.

As organoids emerge as novel tools in biomedical research, we expect that studying and manipulating their mechanobiology
will bring key insight into disease and development processes, and potential new therapeutic targets.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

MSCA-IF-EF-RI - RI – Reintegration panel

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) H2020-MSCA-IF-2017

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Coordinator

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
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.

€ 158 121,60
Address
CARRER BALDIRI REIXAC PLANTA 2A 10-12
08028 Barcelona
Spain

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Region
Este Cataluña Barcelona
Activity type
Research Organisations
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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.

€ 158 121,60
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