Gene expression programmes are critical for eukaryotic development, enabling a single fertilised egg to differentiate into complex adult tissues. This process depends on establishing transcriptionally active euchromatin and transcriptionally silent heterochromatin, whose inheritance across divisions preserves cellular identity: lymphocytes make lymphocytes, neurons make neurons, but never interchange.
The 3D organisation of chromatin in the nucleus underpins these environments. In human cells, heterochromatin localises to the nuclear lamina and peri-nucleolar regions, while euchromatin occupies intervening space (PMID: 34341548). Strikingly, forced relocation of euchromatin to heterochromatic regions results in rapid transcriptional silencing, proving that nuclear compartmentalisation plays an important role in cell-type-specific expression (PMID: 31883795; PMID: 18272965).
Mitosis requires dramatic chromosome condensation, alignment on the metaphase plate, and segregation into daughter cells. How the same nuclear architecture, crucial for preserving cell fate, is rebuilt after such upheaval remains unclear. To address this, your project will apply synthetic chromatin labelling approaches from the Bowman lab (PMID: 30177573, 36066346) to mark heterochromatin domains, together with advanced live-cell imaging and chromosome tracking from the McAinsh labs (PMID: 34932951, 35579370, doi:10.1101/2024.10.17.618897). This integrated approach will follow heterochromatin through mitosis at high temporal resolution, generating a detailed map of domain behaviour from nuclear breakdown to reformation and revealing the cellular mechanisms that safeguard epigenetic memory.
Applicants will apply via the links on our application page: Application.
