Structural basis for DNA loop extrusion by type IV Wadjet systems

Every second, molecular machines inside your cells are pulling DNA into loops, folding the genome into a compact, functional shape—but no one has seen exactly how they do it. This project aims to solve that mystery. The machines in question are SMC complexes, ring-shaped proteins found in all life that organise DNA by extruding loops. Without them, chromosomes would be tangled and genes would not be properly regulated. The researchers will use cryo-electron microscopy to capture atomic-scale snapshots of a bacterial SMC complex called Wadjet, which defends cells by looping and cutting circular plasmids. They will also create hybrid versions of Wadjet and a related E. coli complex, MukBEF, to test what parts of the machine control its different jobs—genome organisation versus defence. This is fundamental science. There is no immediate medical or commercial application. But understanding how SMCs reshape DNA could eventually inform synthetic biology efforts to build custom genome organisers, or explain why human SMC mutations cause developmental disorders and cancers. Past work on similar molecular machines—like the ribosome or CRISPR—shows that seeing a structure clearly often unlocks decades of practical innovation.