Samouil Farhi is a group leader at the Klarman Cell Observatory at the Broad Institute of MIT and Harvard, where he leads the Optical Profiling Platform. He joined the Broad Institute in July 2018 after completing his Ph.D. in chemical biology at Harvard University with Adam Cohen, where he developed methods for all-optical investigations of neuronal systems. The platform’s goal is to bring next-generation imaging approaches to bear on large-scale biological problems, with a focus on profiling the spatial organization of tissues, high-content phenotypic screens and all-optical studies of the electrical properties of cells.

Benjamin Blencowe aims to systematically elucidate the molecular and genetic mechanisms associated with the (mis)regulation and function of a neuronal microexon network frequently disrupted in autism. The methods and datasets generated by the project are expected to provide a framework for future investigations of RNA regulatory networks disrupted in autism as well as in other nervous system disorders and diseases.

Many individuals with ASD have mutations in chromatin modifiers and transcription factors. Neville Sanjana’s team aims to understand how mutations in these genes and in nearby noncoding regions alter chromatin structure and transcriptional regulation, generating a large-scale integrated dataset. Such data is expected to help pinpoint which ASD risk genes will yield the biggest benefit when targeted with gene augmentation therapeutics.

The role of dysregulated chromatin biology in ASD has become increasingly apparent as genome sequencing has implicated numerous epigenetic regulatory genes in ASD etiology. As genome sequencing results in significant rates (approximately 28 percent) of variants of uncertain significance, Rosanna Weksberg and colleagues propose to derive DNA methylation signatures for 23 SPARK genes with known or potential functions in chromatin biology that can be developed into predictive tools to enhance accurate diagnostic classification of such variants.