The goal of this research project is to identify new strategies for the cure of diseases associated with mutations in the tuberous sclerosis complex (TSC). TSC, a tumor syndrome associated with various tissues that include the brain, skin, kidneys, heart, and lungs, affects an estimated 1 in 6,000 to 10,000 births. In addition, varied neurological and cognitive deficits are very common and represent the most severe features of TSC. Currently, TSC therapeutics being tested in the clinic simply block or slow down tumor growth, rather than kill them. Thus, there is an urgent need for new strategies to target TSC. Our research aims at identifying the "Achille's heels" of TSC tumors by identifying combinations of genes that are essential to their growth, but not of wild-type cells. To identify these putative therapeutic targets, we will apply state-of-the-art methods in functional genomics to the fruit fly, Drosophila, a proven model system to study TSC. Findings from this model will guide a set of follow up experiments in mammalian cells to validate these findings, and eventually expanding them to humans.