Despite tremendous efforts to genetically and phenotypically characterize individuals with autism, we are still at the earliest stages of understanding how autism occurs. The vast majority of individuals with autism have mutations in one copy of each of multiple genes (heterozygous mutations), and these mutations interact with each other in ways that we do not yet understand.

Lawrence Zipursky aims to increase understanding of the mechanisms of autism by using neurons in the fruit fly Drosophila melanogaster to explore the relationships among genes implicated in autism. Specifically, Zipursky and his colleagues at the University of California, Los Angeles hope to to recreate combinations of the spontaneous and inherited mutations found in participants in the Simons Simplex Collection (SSC) in Drosophila to discover which of these combinations may play roles in the development of autism.

The researchers plan to use gene expression networks in both Drosophila and humans to identify which pairs of genes are likely to function together. The use of these networks reduces the number of combinations needed, making the number to be tested feasible. After generating flies with mutations in the same combination of genes that have mutations in individuals in the SSC, Zipursky plans to use a series of assays to find defects in neural development. If successful, this project should improve our understanding of how genetic lesions in different genes combine to cause autism.