Federal Project Grant Award Summary

St. Jude Children's Research Hospital Inc. received a $690,296 Project Grant 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), awarded July 1, 2026, with completion targeted for March 31, 2031. The research project, "Decoding Neuron Nuclear Condensation in Differentiation: Imaging & Molecular Insights," focuses on understanding how cerebellar granule neurons (CGNs) undergo nuclear changes during differentiation. The project delivers investigative services and research outputs examining chromatin remodeling, gene expression, and nuclear organization in neuronal development, with the aim of providing insights applicable to neurological disorder therapeutics.

The research employs a three-part strategic approach utilizing innovative epigenetic imaging probes (CMAP) to visualize chromatin reorganization in living neurons, unbiased proteomics to identify chromatin-modifying complexes during early differentiation stages, and advanced microscopy to characterize nuclear organization at unprecedented temporal and spatial resolution. Specific research deliverables include a dynamic model of chromatin dynamics in neuronal differentiation (Aim 1) and identification of molecular pathways promoting nuclear condensation and chromatin compaction, including investigation of histone H1 and the ISWI complex's regulatory roles (Aim 2). These research outputs address critical gaps in understanding dynamic chromatin states in living cells and the mechanisms underlying neuronal differentiation, with potential implications for developing therapeutics for neurological disorders.