R11: Regulation and Role of Physical Properties for Transcriptional Condensates

Whereas our genome is localized in the membrane-enclosed nucleus, membrane-less compartments within the nucleus further establish sections of specialized function. Examples for the latter are repressive chromatin containing polycomb bodies and transcriptional condensates that mediate robust transcriptional activity. Whereas organelles are mainly stable structures, membrane-less compartments formed by phase separation are spatially and temporally highly dynamic, enabling context-specific control of cellular processes such as gene regulation. Various physical models can explain such scenarios; however, little is known about the underlying forces and dependencies regulating these condensates in vivo. In this project, we aim to develop a comprehensive understanding of transcriptional condensates by combining systematic imaging of their components within cells after perturbations with multi-scale modelling; the latter combines a continuous model based on non-equilibrium active-matter physics with a particle-based coarse-grained model. We will address the interplay between important transcription regulators for these condensates, and integrate our findings with physical mechanisms. This will allow us to construct and validate a multi-scale model for transcriptional condensates in an elastic matrix, considering in particular their size and their physical and genomic location, and to decipher the impact of biological and physical mechanisms on their regulation.