A seven-laboratory consortium, headed by Kurt Haas, has established a platform to measure the impact of large numbers of ASD missense variants on protein function in multiple model systems, making best use of rapid high-throughput screening assays and slower high-sensitivity assays to examine the effects of these mutations on vertebrate neuronal development.

Carol Mason’s laboratory recently identified atypical refinement of neurons in the developing visual system in Fmr1 mutant mice. Here, in collaboration with Mimi Shirasu-Hiza’s laboratory, she proposes to investigate whether FMR1 in astrocytes plays a role in this phenotype and to identify the cell-type specific transcriptional changes related to this effect.

Frank McCormick will address the biochemical mechanism by which mutations in SYNGAP1 drive ASD and intellectual disability. Elucidation of the mechanism of SYNGAP1 negative regulation of RAS and its effector pathways in neurons will further our understanding of the role of this pathway in health and disease, and will shed light on potential ways in which targeted RAS pathway inhibition may be therapeutically relevant.

Sung Eun “Samuel” Kwon plans to use a recently developed optical reporter of ERK activity, combined with a neuronal activity reporter, to monitor the dynamics of ERK signaling and neuronal activity in awake-behaving SynGAP mutant mice.