Federal Project Grant Award Summary

Harvard Medical School (President and Fellows of Harvard College) received a $125,000 Project Grant award from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective March 1, 2026, with completion scheduled for February 29, 2028. The award supports fundamental research investigating the molecular mechanisms of transcription-replication conflicts—collisions between transcription and DNA replication machineries that destabilize the genome and contribute to diseases including cancer. The project employs advanced biochemical techniques, computational prediction models (including AlphaFold), and cryo-electron microscopy (cryo-EM) to identify novel factors that resolve these conflicts and define the mechanistic pathways underlying their resolution.

The research program comprises three integrated aims: Aim 1 focuses on using AlphaFold predictions and cryo-EM to identify novel factors recruited to transcription-replication conflicts and visualize their interactions with transcription or replication machinery; Aim 2 involves reconstituting transcription-replication conflicts in vitro to enable direct observation and manipulation of these cellular reactions; and Aim 3 investigates how the Integrator complex coordinates with replication machinery to resolve conflicts. During the K99 phase of the award, the investigator will develop systems for reconstituting and manipulating transcription-replication conflicts. This research directly advances the NIGMS mission to increase understanding of fundamental biological processes that underpin disease prevention and treatment innovation.