1: Characterize genetic network of genes involved in memory and mental retardation using a targeted candidate approach. Understanding the genetic ensemble in which a given gene involved in mental retardation is functioning is key. Genetic pleiotropy implicates that genes are reused but combined differently depending on the function to be achieved. In other words, a given gene will be used with different enhancers or suppressors to create various phenotypes (eg. tissue development or neuronal function). Drosophila genetics allows for rapid identification of modifier genes in a given pathway. Memory and mental retardation are likely to involve multiple genes, making the ability to screen genes fast even more advantageous. Furthermore, Drosophila allows for spatio-temporal dissection of gene function which helps to establish if the cognitive defect observed is caused by the effect of the gene purely during development or adulthood, an essential piece of information for treatment. Importantly, Drosophila is cheap to keep and provide an impressive economy of scale while allowing population genetics and in vivo studies. We will therefore utilize Drosophila mutants for genes involved in mental retardation such as Fragile X syndrome, Angelman syndrome and others, to study epistatic interactions with other genes in the context of memory formation and maintenance. This will allow us to establish a genetic network that can later be used to develop therapeutic. 2: Characterize in Drosophila genes identified in pediatric neurology clinic as involved in learning and memory. From a clinical point of view, we have access to a lot of patient with cognitive disabilities still undiagnosed in term of genetic defect. Recent advances in comparative genomic hybridization allow us to assess copy number variation in patients. This has already opened new avenues of research for autism, schizophrenia and other complex neurological disorders where large family study is not always possible. In addition to leading to higher diagnostic yield, this technique will allow us to identify novel genes that can then be reported and brought back to the laboratory for further study. This translation from the clinic to the bench is extremely important to further our understanding of human cognition. | 
