Mechanisms for Remodelling Chromatin.

Every cell in your body packs two metres of DNA into a nucleus just millionths of a metre across, and specialised enzymes called Snf2-related remodellers actively shift how that DNA is spooled around proteins to control which genes are switched on or off. This project aims to build a detailed structural model of one of these remodelling enzymes in action, showing exactly how it grips a nucleosome—the DNA-protein spool—and uses energy from ATP hydrolysis to pry, slide, or eject DNA segments. The researchers will also use genomics to map which genes different remodelling enzymes target and what specific chromatin changes they produce. This is fundamental science. It addresses a deep gap in understanding: how cells reliably access specific stretches of DNA without tangling the rest. If successful, the work will reveal the mechanical logic behind a process that underpins everything from development to disease—errors in chromatin remodelling are linked to cancers and developmental disorders. There is no immediate practical application, but similar fundamental work on DNA-packaging enzymes has already informed drug design for epigenetic therapies. A clearer picture of these molecular machines could eventually guide strategies to correct misregulated gene expression in human cells.