Project Grant 2204114

The University of Pittsburgh received a $537,317 Project Grant award from the National Science Foundation Division of Chemistry under the Mathematical and Physical Sciences federal grant program (CFDA 47.049). The grant supports the development of activity-based probes for genome-modifying enzymes through an interdisciplinary research project led by Dr. Kabirul Islam. The project aims to uncover novel DNA-modifying enzymes that protect and control genetic information through organic chemistry, mechanistic biochemistry, cell biology, proteomics, and bioinformatics approaches. It will integrate high school, undergraduate, and graduate students, including those from underrepresented groups, to provide training experience for careers in scientific research and development and/or pedagogy. The research focuses on designing first-in-class oligonucleotide probes carrying electrophilic functionalities to capture DNA-modifying factors from embryonic stem cells via complementary reactivity. Subsequent chemoproteomic and bioinformatic analyses and biochemical validation will identify new enzymes and signaling pathways underlying cellular differentiation, lineage commitment, and organismal development. The tools developed will be made available to researchers studying how chemical modifications in DNA store and regulate critical information beyond primary sequences.