Discovering the epigenetic principles of human centromere seeding and inheritance

Every time a human cell divides, it must copy its centromeres—the tiny protein anchors that pull chromosomes apart—or risk creating daughter cells with missing or extra chromosomes. This project tackles a century-old puzzle: how does a cell know where to build exactly one centromere on each chromosome, and how does it faithfully rebuild that same structure after every division? The answer lies in a specialised protein called CENP-A, which marks centromere locations like a molecular flag. The Jansen and Gruszka labs will combine experiments in living cells with lab-made reconstructions to discover the rules that govern how CENP-A chromatin is first assembled, then stabilised, and finally inherited across generations of cells. This is fundamental science with no immediate practical application. But understanding centromere inheritance matters because errors here produce aneuploidy—cells with the wrong number of chromosomes—which drives cancer development and miscarriages. Deeper knowledge could also enable researchers to build human artificial chromosomes from scratch, a tool that would transform gene therapy and synthetic biology. Past work on centromere biology has already shaped how we understand chromosome evolution and genome stability, and this project aims to uncover the core epigenetic principles that make it all work.