Securing funding for research is a significant stressor for scientists. The competition for grants is fierce, and grant writing is an arduous process that takes researchers away from their work. On top of that, the pressure to obtain funding can stifle scientific breakthroughs. For example, some scientists may choose “safer” projects—those that are likely to yield publishable results and thus attract funding agencies—instead of pursuing riskier studies that may have greater potential to produce major advances but also are more likely to fail.

Fortunately for Michael Greenberg, PhD, the Nathan Marsh Pusey Professor and chair of the Department of Neurobiology in the Blavatnik Institute at Harvard Medical School, the Simons Foundation Autism Research Initiative (SFARI) welcomes risk and novelty when reviewing proposals for its Research Awards. The most important criterion for these awards, which provide support for the investigation of key unresolved research questions in autism, particularly those that connect etiology to brain function and behavior, is the potential impact on the autism research field.

“SFARI occupies a unique niche within the autism funding community, supporting a broad range of research approaches,” says Greenberg, who will receive nearly $1.2 million in grant funding as a 2020 Research Award recipient. “Current and past SFARI support has been critically important in allowing us to pursue early-stage studies such as our current project. We are able to test and explore provocative hypotheses when access to alternative funding sources might otherwise prove difficult,” he says.

Neuronal activity triggers the expression of new genes that play a critical role in aspects of neural development and cognitive function. Greenberg’s laboratory has been investigating how dysregulation of this genetic program may contribute to neurodevelopmental disorders such as autism.

“In the case of the current project, we have identified an unexpected link between the stimulus-induced transcription factor Fos and the BAF chromatin remodeling complex when working in fibroblasts,” he says. “We find that Fos recruits BAF to drive a program of stimulus–induced gene expression in these cells.”

Mutations in various components of the BAF complex have been associated with autism as well as a range of other neurodevelopmental disorders. However, the specific mechanisms by which impairment of the BAF complex contributes to autism remain unclear.

“Given that Fos also serves as a major mediator of neuronal activity–dependent gene responses in neurons, the proposed research seeks to test the hypothesis that Fos acts to drive gene expression in response to neuronal activity via BAF recruitment, and that defects in this response might underlie the effects of BAF mutations in autism,” Greenberg says.

Working in both a BAF mutant mouse model as well as a human neuronal culture system, the lab will determine whether autism-associated BAF mutations compromise neuronal activity–dependent gene expression programs. Together, the proposed experiments will provide a better understanding of BAF function and yield insight into the etiology of a range of syndromic and nonsyndromic autism spectrum disorders.