Federal Grant Award Summary

Northwestern University's Sponsored Research Division received a $240,000 Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853), effective June 1, 2026 through May 31, 2028. The research focuses on characterizing the diversity and expression patterns of TRIO (Rho guanine nucleotide exchange factor) isoforms during human synapse development using state-of-the-art long-read sequencing, induced pluripotent stem cell (iPSC) models, and fluorescence imaging techniques. This research addresses a critical gap in understanding how alternative splicing of the TRIO gene produces multiple isoforms with distinct functional domains and domain architectures that regulate synaptic development timing and spatial organization.

The project's primary deliverables include a comprehensive catalogue of TRIO isoform diversity, characterization of their differential expression patterns, and elucidation of their specific roles in human glutamatergic synapse development. These findings are intended to advance understanding of human-specific synaptic mechanisms implicated in neurodevelopmental disorders, as pathogenic TRIO variants are associated with intellectual disability, developmental delay, and seizures. The research outcomes will support gene therapy designs, interpretation of clinical variants, and identification of novel biological mechanisms underlying synaptic pathogenesis, thereby contributing to NINDS's mission to reduce the burden of neurological disease through fundamental knowledge development.