IN researcher Víctor Borrell will coordinate a project to understand how the cerebral cortex folds

26 de October de 2023

• The UNFOLD project has been awarded an ERC Synergy Grant 2023 with 10,8 million euros.
• Researchers seek to reveal what the interaction between physics and biology is like to give rise to the development and shape of living organisms.

The European Research Council (ERC) has selected the UNFOLD project 'Unfolding the dynamic interaction between mechanical and molecular processes in brain folding', as one of the 37 beneficiaries of the Synergy Grants 2023, in which 395 proposals were submitted. The project, which has been endowed with 10.8 million euros, will be coordinated by the Institute for Neurosciences (IN), a joint center of the Spanish National Research Council (CSIC) and the Miguel Hernández University of Elche (UMH), led by the researcher Víctor Borrell, and will be developed in coordination with the University of Erlangen-Nuremberg (Germany), the University of Liège (Belgium) and the Pasteur Institute (France).

In this call, priority is given to addressing ambitious research questions that can only be answered through the coordinated work of several laboratories. The 37 research groups selected will receive €395 million to address some of the world’s most formidable research problems spanning a range of scientific disciplines. The funding helps groups of outstanding researchers to pool different skills, knowledge, and resources to push the frontiers of our knowledge.

The Neurogenesis and Cortical Expansion laboratory, directed by Víctor Borrell, conducts fundamental research on the embryonic development of the brain and, in particular, its growth and folding. This is a characteristic of the human brain that, when defective, leads to very serious learning and intellectual problems. The CSIC Research Professor, who already obtained a Starting Grant from the ERC in 2012 to develop the CORTEXFOLDING project, has emphasized the importance of this achievement, which involves 2.8 million euros for the IN: “Being awarded the Synergy Grant, which is the most competitive and best-funded call for European science, represents great support for the activity that we do and to consolidate our leadership in this field, especially as it is coordinated from the IN”.

Borrell's group will be joined by laboratories directed by Kristian Franze, director of the Institute of Medical Physics and Microtissue Engineering at the University of Erlangen-Nuremberg and of the Max-Planck-Zentrum für Physik und Medizin (Germany), and a pioneering researcher in the field of brain mechanobiology; Laurent Nguyen, one of the most accredited brain development researchers in Europe, who is the elected scientific director of the GIGA Center of the University of Liège (Belgium); and Roberto Toro, a world leader in the development of mathematical models of brain folding and director of the Applied and Theoretical Neuroanatomy unit of the Pasteur Institute (France).

UNFOLD: How is the cerebral cortex folded?

Until now, experts know that folding of the cortex requires the participation of multiple types of stem cells and cell migration processes, controlled by complex genetic developmental programs. They are also aware that the mechanical properties of embryonic brain tissue play a central role in its folding. Importantly, mechanics, cell and genetic biology influence each other constantly and dynamically.

The UNFOLD project will address the question of cortical folding from all these points of view, with a special interest in understanding its complexity. The results of the experiments will be framed in a global computational model that researchers will use to ask specific questions and then find answers.

“Currently there is great interest in understanding the process of cortical folding, but, due to its great complexity, individual research groups have had to focus on studying a specific aspect”, explains Víctor Borrell. The researcher highlights that, thanks to the Synergy Grant, the four laboratories will be able to pool different capacities and knowledge to unify research fields that have traditionally ignored each other.

The result of this union is a strong multidisciplinary team, made up of four laboratories of specialists in cell biology, brain evolution, physical sciences, and computational models, who will generate complete atlases of all cell types, genetic expression programs, and mechanical forces throughout brain development. “Together we will reveal the mysteries of the interactions between physics and biology that give rise to the development and shape of living organisms”, says Borrell.

Researchers will work across species, from amphibians to large mammals, in order to analyse how all these elements interact with each other and give rise to cortical folding.

The Institute for Neurosciences is proud

The director of the Institute for Neurosciences, Ángel Barco, has stated that this achievement by Víctor Borrell represents enormous pride for the institution: “I am sure that, under his coordination, the excellent international and multidisciplinary team that he has assembled to carry out the project will reveal new essential keys to understanding the mechanisms that have allowed the extraordinary evolution of the human brain”. And in this context, he points out that: "Thanks to the execution of UNFOLD we will understand a little better how this amazing structure is generated and we will be able to advance in the understanding of diseases in which abnormal folding occurs during the development of the cerebral cortex"

This will be the fifth ERC project underway at the IN, and the eleventh since the creation of this European funding agency. “The other ERC projects in the process of execution are producing excellent results,” says Ángel Barco. They are MotivatedBehaviors, led by Félix Leroy, which investigates the neural bases of motivated behaviors; CERCODE, led by Juan Antonio Moreno Bravo, which focuses on the development of the cerebellum; XSCAPE, led by Luis Martínez Otero, which studies the interaction between the predictive brain, cultural artifacts and visual exploration; and SPONTSENSE which, under the direction of Guillermina López Bendito, investigates the formation of sensory circuits.

About the ERC

The ERC, set up by the European Union in 2007, is the premier European funding organisation for excellent frontier research. It funds creative researchers of any nationality and age, to run projects based across Europe. The ERC offers four core grant schemes: Starting Grants, Consolidator Grants, Advanced Grants, and Synergy Grants. With its additional Proof of Concept Grant scheme, the ERC helps grantees to bridge the gap between their pioneering research and the early phases of its commercialization.

The ERC is led by an independent governing body, the Scientific Council. Since November 2021, Maria Leptin has been the President of the ERC. The overall ERC budget from 2021 to 2027 is more than €16 billion, as part of the Horizon Europe programme, under the responsibility of European Commissioner for Innovation, Research, Culture, Education and Youth, Iliana Ivanova.

More information: https://unfold-lab.github.io/

Sources: Institute for Neurosciences CSIC-UMH (in.comunicacion@umh.es) / ERC Press

Sant Joan d’Alacant, 26^th October, 2023