Federal Project Grant Award Summary

Cornell University's Office of Sponsored Programs received a $482,612 Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective July 1, 2026, through April 30, 2030. The award supports fundamental research to decipher regulatory syntax governing gene transcription by analyzing computational models that predict how DNA sequence motifs encoding transcription factor binding sites control transcriptional activity. The project develops advanced interpretation tools to uncover syntax rules that govern interactions between transcriptional activators, repressors, and DNA sequence elements that direct preinitiation complex (PIC) assembly, RNA polymerase II (Pol II) pausing, and nucleosome positioning—specifically addressing how steric constraints determine the correct positioning and orientation of transcription factors relative to Pol II and nucleosome complexes.

The research builds on the investigators' development of CLIPNET, a machine learning model that identifies intricate motif syntax relationships and accurately explains how DNA sequence governs transcription initiation at human cis-regulatory elements. Primary deliverables include comprehensive analysis of computational models to identify generalizable regulatory syntax rules, determination of whether syntax constraints are conserved among transcription factors with similar activation domains, and empirical validation of the computational predictions through advanced interpretation methodologies. The work addresses a fundamental gap in understanding gene regulation, as few generalizable rules have emerged regarding regulatory syntax despite prior research focusing on transcriptional activator interactions.