Epilepsy and Migraine Integrated Network (EMINet)

The main aim of this consortium is to identify and better understand the intricate genetic and molecular networks implicated in the etiology of two closely related complex inherited disorders of disturbed brain excitability, i. e. epilepsy and migraine. By analyzing large and well characterized patient samples as well as cell and animal models with genetic, genomic, biochemical, molecular, and physiological techniques we will enhance our currently limited knowledge about genetic susceptibility and molecular pathways in these common and disabling brain disorders. To be able to reach this goal, the combination and close interaction of different medical and scientific specialties is needed. We have therefore established a network of partners with complementary expertise allowing a comprehensive work-chain starting from the identification of susceptibility genes by whole-genome association (WGA) studies over the analysis of associated variants in cell- and tissue-models to the generation and analysis of respective animal models. The proper understanding of underlying genetic and molecular mechanisms of disease development will in turn be of importance for the future optimization and individualisation in medical counselling and support of patients and families.

The project started with

(i) the execution and statistical analysis of WGAs and replication studies in large patient samples afflicted by idiopathic generalized epilepsies and common forms of migraine and

(ii) the detailed biochemical, physiological, and phenotypic investigation of already established cell and mouse models for monogenic, highly penetrant forms of both disorders.

Subsequentlywe transfer the novel susceptibility genes/genetic variants identified by WGA into suitable cell and animal models, which again will be comprehensively investigated in a cooperation of different partners of the consortium.

These studies are complemented by high-throughput sequencing studies using next-generation sequencing technologies and by genetic and functional studies addressing drug-response and adverse drug effects. Newly identified rare genetic variants implicated in disease pathogenesis or individual drug-response are also transferred and analyzed in appropriate model systems. This consortium will thus contribute to the overall goal of improved medical care by an in-depth understanding of complex molecular pathways affecting the regulation of brain excitability.

Latest results can be found in detail in the descriptions of the subprojects