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Unfolding the dynamic interplay of mechanical and molecular processes in brain folding

Objective

Mammals with large brains and higher cognitive functions have a richly folded cerebral cortex. Folding abnormalities are linked to various cognitive disabilities. Despite its relevance in clinical diagnostics, the causes and consequences of cortex folding remain poorly understood. While cortex folding was long assumed to result from a limited skull volume, it is a developmental process intrinsic to the cortex. We hypothesize that cortex folding emerges from a dynamic interplay between mechanical and molecular processes, and that far from being an epiphenomenon, it has major consequences for brain architecture and function. UNFOLD will test this hypothesis by integrating genomics, cell biology, mechanics of brain development and computational modeling. Our interdisciplinary team will apply in vitro, in vivo and in silico approaches to brain tissue of strategically selected animal models. First, we will map molecular, cellular, and mechanical events accompanying cortex folding. Next, we will investigate the effects of genetic perturbations of cell biological processes on tissue mechanics, and vice versa, to identify key mechanisms leading to cortex folding and elucidate their dynamic interactions. Then, we will test the universality of these mechanisms by inducing folds in species with a smooth brain. Finally, we will decipher the consequences of cortex folding on neural circuit function and animal behavior. Our project integrates current, opposing concepts of cortex folding by adopting an interdisciplinary and multiscale perspective. Unraveling the dynamic interactions between molecular, cellular, and mechanical events during development will provide unprecedented insights into the determinants of cortical anatomy and brain organization. Our work, bridging physical and life sciences, will lead to new insights into normal and pathological brain development, paving the way to a new research area of integrated neurobiology with potential applications in modern medicine.

Fields of science (EuroSciVoc)

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Keywords

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Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

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.

HORIZON-ERC-SYG - HORIZON ERC Synergy Grants

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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) ERC-2023-SyG

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Host institution

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
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.

€ 2 741 588,75
Address
CALLE SERRANO 117
28006 MADRID
Spain

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Region
Comunidad de Madrid Comunidad de Madrid Madrid
Activity type
Research Organisations
Links
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.

€ 2 741 588,75

Beneficiaries (4)

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