Federal Grant Award Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded the Regents of the University of Michigan a Project Grant totaling $601,750 under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, effective June 12, 2026, with a completion date of March 31, 2031. The University of Michigan will develop and apply VISTA-FISH (Video Imaging with Spatial-Temporal Analysis by FISH), an innovative technology that integrates live-cell microscopy with high-resolution spatial transcriptomic profiling to simultaneously measure gene expression, cellular morphology, and functional behavior in individual neurons. This approach enables direct linkage of neuronal gene expression profiles to functional outcomes and cellular phenotypes.

The research will utilize induced pluripotent stem cell (iPSC)-derived human neurons carrying TDP43 and C9ORF72 mutations to identify molecular pathways underlying vulnerability and resilience to neurodegeneration. Specifically, the project will record TDP43 localization and neuronal activity during aggregation-inducing stimuli, measure single-cell gene expression in the same cells, and combine live-cell measurements of TDP43 protein dynamics with CRISPR screening to determine transcriptomic changes associated with protein aggregation, synthesis, and degradation. The resulting rich datasets will provide unprecedented molecular insights into factors driving neurodegeneration susceptibility and protection at the single-cell level.