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Inducing functionality in retinal organoids with electrical activities derived from developing retina

Project description

Advancing retinal organoids

Organoids are stem cell-derived tissue cultures that resemble the microanatomy of the native organ. However, the complexity of the retina in terms of neuronal connectivity and response to different light stimuli has not been fully recapitulated by organoids. The scope of the EU-funded NeuFRO project is to overcome current limitations in retinal organoids and offer the diversity of functions of the native retina. To achieve this, researchers will record the events underlying the functional maturation of the retina during development with spatiotemporal precision. A model will combine the obtained information and decode it into retinal organoids to provide the necessary electrophysiological events for generating functional retinal organoids.

Objective

Deriving mammalian retina from stem cells has had a large impact on the study of the biology of vision and is called organoid. Compared to in vivo retina, retinal organoids are far less functionally sophisticated in terms of their synapses, connectivity, discrimination between different light stimuli and their electrical action potentials. This project will overcome this functional constraint of retinal organoids by studying electrophysiological events-derived functional maturation of mouse retina during retinal development and then stimulating those events with the help of mathematical models in order to induce the same functionality in mouse and human retinal organoids. NeuFRO will achieve a resonance in the field by generating retinal organoids with the neuronal connectivity and the natural diversity of functions using interdisciplinary fields including electrophysiology, developmental biology, and computationally-derived electrical stimulation.

Initially, I will create a holistic roadmap of the electrical features of immature mouse retina during development that shows self-organization through electrophysiology. With milli- to nanometer imaging precision, electrical activities derived the circuit formation will be spatiotemporally documented. Then I will decode this space-time code of intrinsic electrical patterns and neuronal connectivity using an ambitious strategy incorporating Hodgkin-Huxley and linear-nonlinear models. Next, such electrical response models will be applied to immature retinal organoids (mouse and human) by an innovative ‘sandwich’ electrophysiology technique during the development in vitro. With this approach, I will induce naturalistic electrical features in the retinal organoid, allowing the functional neurons to wire and fire appropriately into retinal organoids, particularly visual circuits. This ground-breaking approach will advance techniques for generating functional human retina.

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-2021-STG

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Host institution

STICHTING RADBOUD UNIVERSITAIR MEDISCH CENTRUM
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.

€ 1 498 364,00
Address
GEERT GROOTEPLEIN 10 ZUID
6525 GA NIJMEGEN
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
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.

€ 1 498 364,00

Beneficiaries (2)

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