High Content Image Analysis Identifies Novel Regulators of Synaptogenesis in a High-Throughput RNAi Screen of Primary Neurons

The formation of synapses, the specialized points of chemical communication between neurons, is a highly regulated developmental process fundamental to establishing normal brain circuitry. Perturbations of synapse formation and function causally contribute to human developmental and degenerative neuropsychiatric disorders, such as Alzheimer's disease, intellectual disability, and autism spectrum disorders. Many genes controlling synaptogenesis have been identified, but lack of facile experimental systems has made systematic discovery of regulators of synaptogenesis challenging. Thus, we created a high-throughput platform to study excitatory and inhibitory synapse development in primary neuronal cultures and used a lentiviral RNA interference library to identify novel regulators of synapse formation. This methodology is broadly applicable for high-throughput screening of genes and drugs that may rescue or improve synaptic dysfunction associated with cognitive function and neurological disorders.National Institutes of Health (U.S.) (MH095096)National Institutes of Health (U.S.) (R01 GM089652

A combined cellomics and proteomics approach to uncover neuronal pathways to psychiatric disorder

Studying biological mechanisms underlying neuropsychiatric disorders is highly challenging as many risk genes are associated with these disorders. This complexity requires research approaches to reliably dissect the cell biology of the risk genes involved. Here, we describe a combined cellomics–proteomics approach that allows (a) medium-throughput functional screening and unbiased selection of important risk genes, and (b) discovery of common functional pathways and interactome connections of selected risk genes. The overlay of pathway and proteome data from selected genes in a biological context can be used to formulate new testable hypothesis of both the genetics and the biology of the disorders