Chromatin Organisation and Cellular Identity
This MPhys project investigates how the three-dimensional organisation of chromatin influences transcriptional dynamics and cellular identity. Although all cells share the same genome, they adopt and maintain distinct identities, suggesting that physical organisation within the nucleus plays an important regulatory role beyond biochemical epigenetic marks alone.
Using polymer-based simulations of chromatin folding driven by bridging-induced phase separation (BIPS), the project models how multivalent transcription factors can generate dynamic clusters and transcriptional hubs without requiring direct protein–protein attraction. Different chromatin organisations, loosely motivated by stem-like, differentiated-like, and senescent cellular states, are constructed and compared within a unified physical framework.
To connect chromatin structure to gene activity, transcription is modelled as a stochastic on–off process and analysed using the telegraph model. By extracting effective switching rates and burst statistics from simulated transcriptional time series, the project quantifies how changes in chromatin organisation are reflected in transcriptional variability and stability. The broader aim is to assess whether physical mechanisms of chromatin folding can help shape the effective regulatory landscape underlying cellular identity.