Project Summary In its most basic form, this proposal will explore the effects of human disease through the use of a fly model to generate fly avatars of severe epileptic disease. The form of epilepsy that will be modeled here is Developmental and Epileptic Encephalopathy (DEE)—a pediatric epileptic condition that causes severe early onset epilepsy. By making mutations, the goal is to generate a fly model and use it to generate insights into epileptic mechanisms. Then, with the construction of CRISPR generated platform for recombinase generated mosaics, mosaics can be generated for the DEE mutants that explore tissue sensitivities. The long-term goal is to improve the understanding of these epilepsies and what increases or decreases their occurrences. Using the recombinase-based mosaicism, there exists a real possibility to delve into the cell biology of the molecules that predispose an organism to epileptic seizures. The ultimate goal is to understand these specific epilepsies, what promotes them and how can tailored therapies be generated from a better understanding of their mechanisms. The hope is that ultimately these discoveries lead to a targeted drug therapy.