GRK 3151:  Development and epileptogenesis of dysplasias in the interplay of distinct CNS cell types

• Subject Area: Neurosciences
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 548594750

Focal cortical dysplasias (FCDs) are increasingly diagnosed neurodevelopmental disorders associated with drug-resistant epilepsy and cognitive and behavioral impairment. Surgery is often the only treatment option but is restricted to a fraction of patients. Increasing knowledge of the genetic basis of dysplasias has only led to limited improvements in treatment so far. A deeper understanding of how basic mechanisms of neurodevelopment are exploited by nascent malformations to contribute either to dysplasia formation or to the creation of a structurally and functionally impaired network environment is needed to provide better treatment perspectives. Pathomorphologic studies of FCD biopsies suggest strongly linked key neurodevelopmental processes with putative high relevance in this context: Neurovascular communication, microglia-neuron interaction, neurite and synapse plasticity, and monoaminergic signaling. The overall goal of this RTG is to elucidate the role of these mechanisms in the emergence of the clinically most challenging FCD variants and in their phenotypic manifestations including seizures and memory impairment. Based on the resulting novel pathogenetic insights, the RTG aims to develop new treatment strategies. Therefore, a new generation of PhD and MD students will be trained to integrate highest level skills in basic neuroscience with profound knowledge of the clinically relevant context of their research. Our interdisciplinary team, which includes researchers from the fields of neuroscience, immunology and vascular biology, as well as expert clinicians, will combine studies in state-of-the-art mouse models, human brain biopsy dysplasia slice cultures and organoids to promote junior scientists in MD and PhD projects. The projects will investigate how FCD formation and phenotypic manifestation are modulated by vascularization and angiogenic factors, altered microglial function due to genetic or acquired causes, and the interaction of these mechanisms with neurite outgrowth and synapse formation with a focus on monoaminergic innervation. Our analyses will focus on clinically highly relevant types of dysplasia and their perilesional microenvironment. The results will be translated into novel experimental therapies involving immunomodulatory photopharmacological approaches analyzed in in-vivo mouse or human biopsy-derived ex-vivo models. The PhD and MD projects will be embedded in an innovative teaching and training environment of the RTG, which promotes interdisciplinarity through various elements, including tailor-made clinical rotations for PhD students, intensified peer learning and international project stages in excellent partner laboratories. Overall, this RTG aims to substantially improve our understanding of the interplay of different cells in FCD pathogenesis and epileptogenesis, to develop innovative therapeutic concepts, and to prepare PhD and MD students for careers as 'Medical Scientists' or 'Research Clinicians'.

• DFG Programme: Research Training Groups
• Applicant Institution: Rheinische Friedrich-Wilhelms-Universität Bonn
• Participating Institution: Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE)
• Spokesperson: Professor Dr. Albert Becker
• Participating Researchers: Professor Dr. Heinz Beck; Professorin Dr. Sandra Blaess; Professor Dr. Frank Bradke; Professor Dr. Özgün Gökçe; Professorin Dr. Elvira Mass; Privatdozentin Dr. Julika Pitsch; Professorin Dr. Stefanie Poll; Professorin Dr. Carmen Ruiz de Almodóvar Egea; Privatdozent Dr. Matthias Schneider; Professorin Dr. Susanne Schoch McGovern; Professor Dr. Michael Wenzel