Although researchers have identified several genes that contribute to autism, there has been little progress in pinpointing the brain cell types and circuits that are affected by mutations in these genes. Nathaniel Heintz, Paul Greengard, and their colleagues are testing a hypothesis that they can identify cells preferentially affected by mutations in autism-linked genes by analyzing their molecular profiles in mouse models of autism. The researchers previously developed a new approach to molecular profiling, called "translating ribosome affinity purification," or TRAP. The technique allows messenger RNA molecules to be captured in the process of being translated into proteins, yielding a global snapshot of the proteins that are being expressed in a given cell type. The team plans to use TRAP to identify changes in the protein profiles of brain cells in mice with one of three mutations in SHANK3, a gene that has been linked to autism in people. The researchers then plan to compare how the different mutations affect protein expression among the different cell types, including neurons from the frontal cortex, striatum and cerebellum areas of the brain.