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 program. This fundamental research project, in which Laurent Nguyen's team from the University of Liège is participating, will be funded with over 10 million euros to decipher the mechanisms of cerebral cortex folding. Together the partners will pay special attention to the complex interplay occurring between biological and mechanical processes that drive folding, thereby providing a deeper understanding of the development and formation of our brain.
MPammals with large brains and higher cognitive functions have a richly folded cerebral cortex. Abnormalities in the folding of the cortex in humans lead to various cognitive disabilities. Despite their importance for clinical diagnosis, the causes and consequences of cortical folding remain poorly understood. While it was long assumed that cortical folding resulted from a limited cranium volume, it is a developmental process intrinsic to the cortex. The folding of the cortex requires the contribution of several types of progenitor cells and the process of cell migration, controlled by complex genetic development programs. The mechanical properties of embryonic brain tissue also play a central role in its folding.
“With the UNFOLD project, we hypothesise that cortical wrinkling emerges from a dynamic interaction between mechanical and molecular processes and that, far from being an epiphenomenon, it has major consequences for the architecture and function of the brain," explains Laurent Nguyen, FNRS Research Director and new Scientific Director of the GIGA at ULiège. “Thanks to this ERC funding, we will be able to test this hypothesis by integrating genomics, cell biology, the mechanics of brain development and computer modelling". The interdisciplinary team includes researchers from the Institute of Neuroscience at the Miguel Hernández University in Elche (UMH), the University of Erlangen-Nuremberg (Germany), the University of Liège (Belgium) and the Institut Pasteur (France). Together, they will apply in vitro, in vivo and in silico approaches to the brain tissue of strategically selected animal models. "We will study the effects of genetic perturbations of cellular biological processes on tissue mechanics and vice versa to identify the key mechanisms leading to cortical folding and elucidate their dynamic interactions. We will then test the universality of these mechanisms by inducing folds in species with smooth brains (lissencephalic)." The results of the experiments will be integrated into a global computer model that the researchers will use to find answers.
The UNFOLD project team will attempt to decipher the consequences of cortical folding on the function of neuronal circuits and animal behaviour. The project integrates current opposing concepts on cortical folding by adopting an interdisciplinary and multi-scale perspective. Elucidating the dynamic interactions between molecular, cellular and mechanical events during development will provide unprecedented insights into cortical anatomy and brain organisation determinants. This ambitious research project, which links the physical and life sciences, will better understand normal and pathological brain development, paving the way for a new field of research, integrated neurobiology, with potential applications in modern medicine.
The UNFOLD project will be coordinated by Victor Borrel, director of the Neurogenesis and Cortical Expansion Laboratory at the Neuroscience Institute (Universitas Miguel Hernandez /CSIC), which conducts fundamental research into embryonic brain development and, in particular, its growth and folding. 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), is a pioneering researcher in the field of brain mechanobiology, Laurent Nguyen, one of Europe's most accredited researchers in the field of brain development, is Scientific Director of the GIGA center at the University of Liège (Belgium); and Roberto Toro, world leader in the development of mathematical models of brain folding and Director of the Applied and Theoretical Neuroanatomy Unit at the Institut Pasteur (France).
The GIGA is a biomedical research center at the University of Liège. It aims to develop research and have a real impact on health. Its main research areas are cancer, neuroscience, infection, immunity and inflammation, and cardiovascular disease. It is structured in 10 thematic research units, which together employ more than 600 people from 6 faculties (Medicine, Science, Applied Science, Veterinary Medicine, Gembloux Agro Biotech, and Psychology), representing some 40 nationalities. This interdisciplinarity and the interactions it generates are one of the GIGA's main strengths. The research center is located directly within the CHU de Liège, making it the only research center in the French-speaking Community of Belgium to be closely associated with a university hospital, thus maintaining constant links between fundamental research and clinical practice. Close collaboration with the CHU's clinicians over several years has enabled the development of effective translational research.
ERC Synergy Grants bring together two to four research institutions working together and bringing different skills and resources to tackle ambitious research problems. In this call, priority was given to ambitious research questions that can only be solved by the coordinated work of several laboratories. The 37 research groups were selected from 395 project submissions and will share €359 million to tackle some of the world's most challenging research problems across a range of scientific disciplines. The funding helps outstanding groups of researchers pool their skills, knowledge and resources to push back the boundaries of our knowledge.
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