FOR 2715:  Epileptogenesis of genetic epilepsies

• Subject Area: Medicine
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 377782854

Epilepsy is a common, severe, and disabling condition with a significant disease burden worldwide. Despite many available treatment options, the seizures are not well controlled in one third of all patients with epilepsy. Gene discovery and first functional analyses of genetic defects have been major drivers to unravel disease mechanisms in the last 20 years and have brought about the first personalized treatment options. However, most of the genetic alterations underlying epilepsy remain to be elucidated and the mechanisms driving a healthy into an epileptic brain are not well understood. A common feature of genetic epilepsies is the typical age dependency the origin of which is largely unknown and which differs between syndromes. Therefore, developmental factors are likely to play a pivotal role for epileptogenesis of genetic epilepsies.In this Research Unit (RU), we aim to investigate if and how genetic mutations induce a cascade of multidimensional epileptogenic processes, such as transcriptional, cellular (morphological, neurophysiological), and network changes, and how these interact with developmental processes which likely contribute to the age-dependent manifestation of seizure and behavioral phenotypes in genetic epilepsies.

• DFG Programme: Research Units
• International Connection: Denmark, Luxembourg, Norway

Projects

• Brain region-specific epileptogenesis in a conditional mouse model (Applicants Lerche, Holger ;  Wuttke, Thomas )
• Centralized data management and analysis facilities (Applicant Isbrandt, Dirk )
• Common and pleiotropic genetic factors in epileptogenesis (Applicants Nothnagel, Ph.D., Michael ;  Schulz, Herbert )
• Coordination Funds (Applicant Lerche, Holger )
• Coordination project (Applicant Lerche, Holger )
• Epileptogenesis and drug discovery in genetic epilepsy models in zebrafish (Applicant Skupin, Alexander )
• Functional epigenomic dissection of genetic generalized epilepsies (Applicants Becker, Albert ;  Sander, Thomas )
• Generation and characterization of new mouse models and transcription profiling (Applicant Ott, Thomas )
• Genetic mechanisms of epileptic encephalopathies (Applicants Helbig, Ingo ;  Weber, Yvonne )
• Hippocampal integration during epileptogenesis of genetic epilepsies: Developmental intervention (Applicants Beck, Heinz ;  Kelly, Ph.D., Tony )
• Mechanisms of epileptogenesis in KCNA2-/SCN2A-mediated epilepsies (Applicants Garaschuk, Olga ;  Hedrich-Klimosch, Ulrike )
• Molecular and network mechanisms-derived targeted interventions in neonatal genetic epilepsies (Applicants Becker, Albert ;  Isbrandt, Dirk )
• Rare genetic factors in epileptogenesis (Applicant Lerche, Holger )

• Partner Organisation: Fonds National de la Recherche
• Spokesperson: Professor Dr. Holger Lerche