The focus of our laboratory is directed towards understanding 1) the signaling events and molecular mechanisms involved in the formation of neuronal connections during development, and 2) the molecular mechanisms underlying changes in or loss of neuronal connectivity during neurological disease (in particular epilepsy). Our investigations concentrate on mouse and humanized cell models (iPS) using an integrated approach involving molecular cell biology, neuroanatomy, (in vivo) functional proteomics, imaging, HC screening, and mouse genetics. We are performing genome-wide miRNA screens in patient-derived brain material and genome functional screens using miRNA libraries to dissect the role and mechanism-of-action of miRNAs in the developing and diseased nervous system, with an emphasis on a role for miRNAs in regulating neuronal connectivity. Functional studies of miRNAs (reporter assays, knockdown/overexpression in neurons (in culture and in vivo), neuronal connectivity, target finding) in the normal situation and during epileptogenesis using molecular, cell biological and mouse genetic approaches. High-throughput microscopy screens in neurons using lentiviral miRNA libraries. Genome wide miRNA profiling of human patient material.