European grants for two Radboudumc projects on Brain-on-Chip technology
hDMT researchers Hans van Bokhoven and Nael Nadif Kasri from Radboudumc and the Donders Institute for Brain, Cognition and Behaviour have received funding from the prestigious European Research programs ERA-NET Neuron and E-Rare.
With the EU-projects DECODE! and IMPACT they build on the innovative Brain-on-Chip technology that has been developed in their groups. For example, they have developed techniques for generating neurons from blood-derived human (patient) stem cells. These induced neurons (iNeurons) are driven to form networks on chips, which allow the study of normal and disease-related neural network properties. With the funding granted by the EU the consortia aim to get insight into the mechanisms of disease of genetic brain disorders and the application of this knowledge for future treatments.
DECODE! Autism spectrum disorder
The ERA-NET Neuron project DECODE!: Decrypting Cadherin-13 function in cortico-cerebellar circuitry underlying is led by Nael Nadif Kasri and aims to gain insight into the mechanism of autism spectrum disorder (ASD), a heterogeneous group of neurological disorders. The recent progress in human genetics has led to the identification of hundreds of genes that are associated with autistic-like behaviour. In particular, rare genetic variations in the protein cadherin-13 (CDH13) were linked to ASD. CDH13 mainly plays a role at the location where neurons communicate with each other: in the synapse.
The consortium will focus on which specific changes in the function of the brain are caused by variations in the CDH13 gene that have been associated with ASD. To this end, they will use mouse models and Brain-on-Chip technology utilizing patient-derived stem cells (iPSCs). Ultimately, this will help to design a targeted treatment of specific ASD symptoms for precision medicine. This project is a collaboration with research groups in Germany, France and Canada.
IMPACT looking for chromatin mutations
Hans van Bokhoven coordinates the E-Rare IMPACT project, which stands for Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy. The project is a collaboration with Italy, Canada, Austria, France and Belgium.
The consortium focusses on neurodevelopmental disorders (NDDs) which represent a large and heterogeneous group of rare disorders. Individual types of NDDs are typically rare, owing to the very high number of individual mutated genes that are causative for such conditions. Among these mutated genes, most are involved in two broad functional domains: synaptic processes and chromatin regulation.
The IMPACT project aims to discover common molecular and cellular signatures of chromatinopathy gene disruptions. Such converging mechanisms of disease offer an attractive target for the development of knowledge-based therapeutic interventions. Here fore, they integrates stem cell research, brain on dish technologies (brain organoids) and omics approaches.