Nuclear envelope transmembrane protein regulation of tissue-specific genome organisation and cell cycle regulation.

Every cell in the human body shares the same DNA, yet a liver cell and a muscle cell behave completely differently—because proteins in the nuclear envelope, the membrane surrounding the nucleus, help organise chromosomes in tissue-specific ways. This project aims to understand how those proteins control genome organisation and cell division. The problem is that we know very little about how the nuclear envelope’s protein composition varies between tissues, or how that variation drives specialised cell behaviour. The researchers previously discovered hundreds of previously unknown nuclear envelope proteins, many unique to specific tissues, and found that liver-specific proteins actively reposition chromosomes—a pattern lost when those proteins are removed. This suggests a fundamental mechanism linking envelope proteins to tissue identity. If successful, this work will reveal how muscle and fat cells organise their genomes during development, and identify the molecular handles that allow envelope proteins to move chromosomes. It may also uncover genetic causes of muscular dystrophy: the team will sequence genes for envelope proteins that affect the cytoskeleton in patients with unexplained forms of the disease. This is primarily fundamental science, but understanding how cells maintain their specialised identity could eventually inform regenerative medicine or therapies for tissue-degenerative conditions.