Federal Project Grant Summary

The National Institute of Neurological Disorders and Stroke (NINDS) awarded The Regents of the University of Colorado a Project Grant totaling $539,064 on July 1, 2026, under the Extramural Research Programs in the Neurosciences and Neurological Disorders program (CFDA 93.853). The award supports a one-year research initiative (through June 30, 2027) investigating the functional role of the intervening domain (ID) in methyl CpG-binding protein 2 (MECP2), a protein whose mutations are associated with serious neurological conditions including Rett syndrome, autism, intellectual disability, and microcephaly. The research deliverables include biochemical and biophysical characterization of MECP2's RNA-binding capabilities, analysis of how RNA binding modulates MECP2's genomic occupancy, and mechanistic studies examining the interplay between RNA binding and DNA binding domains in regulating gene expression during neural differentiation.

The project employs multiple research methodologies across three planned aims to test the hypothesis that the MECP2 intervening domain binds RNA to fine-tune gene expression during brain development. Deliverables encompass experimental work using human stem cells and cortical organoids, molecular and cellular phenotypic analysis of intervening domain mutations, and functional studies examining how disrupted RNA binding impacts neuronal differentiation. The research is conducted at the University of Colorado's Boulder, Colorado location and is designed to advance understanding of MECP2-related neurological disease mechanisms and potentially inform therapeutic development strategies.