Project Grant R01GM160762

The National Institute of General Medical Sciences awarded the University of Texas at Austin $491,703 in Project Grant funding on September 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to support research on the molecular mechanisms of cohesin-mediated three-dimensional genome organization.

The recipient will conduct mechanistic studies of how the cohesin complex, the architectural protein CTCF, its unloading factor WAPL, and regulatory RNAs collaborate to establish and remodel DNA loops that organize genetic information in space and time. The work encompasses three integrated aims: establishing biophysical rules governing how CTCF integrates DNA and RNA binding to specify loop boundaries through massively parallel profiling; reconstituting and directly visualizing CTCF-RNA cluster recruitment of cohesin and force-resistant loop formation at the single-molecule level; and determining the mechanism by which WAPL antagonizes CTCF-RNA clusters to disassemble loops. Mechanistic insights and protein variants from in vitro studies will be validated in mouse embryonic stem cells.

The award supports fundamental research addressing how mutations in cohesin subunits lead to developmental disorders and cancers, with the long-term goal of defining molecular mechanisms underlying dynamic genome organization to maintain human health. Work will be performed in Austin, Texas, with a period of performance from September 1, 2026, through August 31, 2030.