Happy to share our new paper on TnpB, now out in @MolecularCell ! 🧬🔓🌱 This work was co-led by @ZehanZhou, Iren Saffarian-Deemyad, @TrevorWeiss480, and me. We wanted to understand why TnpBs, despite being remarkably compact RNA-guided nucleases, often show limited genome-editing activity. Using single-molecule rotor-bead tracking, we found that Ymu1 TnpB unwinds its DNA target step by step, and that reaching and maintaining the fully unwound state is a major bottleneck. 🔬 By stabilizing these unwound states, we engineered a TnpB variant that cleaves DNA faster and improves genome editing in Arabidopsis. ☘️ This project brought together single-molecule biophysics, biochemistry, protein engineering, and plant biology. I’m very grateful to all our co-authors and to everyone in the Jennifer Doudna, Zev Bryant, and Steve Jacobsen labs who made it possible, as well as the broader communities at the Innovative Genomics Institute, @berkeleyMCB , @bioe_stanford , @UCLA , and @hhmi_science. For me, this work is a wonderful example of what interdisciplinary and collaborative science can make possible. 🤝 🌟 Papers 👉 cell.com/molecular-cell/abst… #TnpB #GenomeEditing #CRISPR #ProteinEngineering #Biophysics #Biochemistry #SingleMolecule #CollaborativeScience #Collaboration #PlantBiotechnology #PlantBiology #TeamScience