Project Grant 2337728

The National Science Foundation (NSF) awarded a 5-year, $399,835 CAREER grant under the Biological Sciences program (CFDA 47.074) to the Massachusetts Institute of Technology (MIT) to investigate how transcription and loop extrusion regulate 3D genome structure. The project aims to improve the understanding of how a single genome gives rise to diverse cell types by studying the dynamics of CTCF-mediated DNA loops and topologically associating domains (TADs). The work will integrate advanced imaging, genome editing, and 3D genomics approaches to quantify TAD and loop formation and dynamics in living cells. Key research questions explore how nested TAD structures and higher-order interactions form, how cohesin abundance and residence time control TADs and loops, and whether transcription positively or negatively regulates these 3D genome features. The grant also includes an education component with students building their own microscopes and studying DNA looping, as well as outreach efforts targeting high school students and underrepresented groups in STEM.