Project Details
Projekt
Active microemulsification as a principle of chromatin organization and its role in cell fate induction
Subject Area
Biophysics
Term
from 2019 to 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 419138152
The eukaryotic genome is spatially organized in a widely conserved nuclear architecture of inactive and active compartments that are segregated but finely interspersed. This architecture dynamically adjusts to gene expression: newly induced genes become localized to the active compartment and unfold, repressed genes become localized to the inactive compartment and are compacted. Recent work, including our own, has suggested phase separation and physics of microemulsions as two principles that might establish and maintain this dynamic architecture. However, the biological relevance of this architecture remains elusive. A common, though untested hypothesis is that the unfolding of specific genomic regions facilitates the regulatory access of signaling proteins, such as transcription factors. Here, we will investigate (i) the role of microemulsion-like reorganization of newly induced genomic regions in embryonic cell fate specification and (ii) the fundamental physical principles by which active cellular processes drive this microemulsion-like reorganization of chromatin. Specifically, we will use mesendodermal cell fate induction in primary culture of zebrafish embryonic cells as an experimental model system, apply live and super-resolution microscopy, and develop a non-equilibrium physical theory of chromatin unfolding by microemulsification. Our work will be one of the first to investigate how physical principles of 3D genome organization contribute to the regulation of gene expression. Further, our theoretical efforts will advance our understanding how active molecular processes such as transcription can impact micro-phase separation in the cell.
DFG Programme
Priority Programmes
