Genome control by cohesin ligands

Every human cell packs two metres of DNA into a nucleus just a few millionths of a metre wide, and a protein complex called cohesin is the machine that folds it into the correct shape. Without this folding, genes cannot be switched on or off properly, DNA cannot be copied or repaired, and chromosomes cannot be separated when cells divide. Scientists know that cohesin extrudes loops of DNA and accumulates at specific sites, but they do not understand how one protein complex manages so many different jobs. This project will combine structural biology, biochemistry, cell imaging, and studies in model organisms to map the network of proteins that control cohesin’s activity. The goal is to connect the atomic structure of these protein interactions to what happens inside living cells and whole organisms. This is fundamental science with no immediate practical application. However, similar work on DNA-folding machinery has already revealed why certain mutations cause developmental disorders and cancers. A clearer picture of how cohesin is regulated could eventually explain why those mutations lead to disease and point toward ways to intervene.