Active Microemulsification as a Principle of Chromatin Organization and its Role in Cell Fate Induction

The cell nucleus displays a striking, widely conserved spatial compartmentalization. Inactive regions of the genome are sequestered to and compacted within a distinct comparment; active regions of the genome are unfolded and occupy another compartment. Recent work has demonstrated that this architecture is established by physical process. In particular, actively transcribed regions of the genome are unfolded similar to the physical process of microemulsification. In this project, we aim to investigate (i) how microemulsification might contribute to the rapid induction of genes in zebrafish mesendoderm formation, and (ii) how non-equilibrium processes shape bring about unique properties otherwise not seen in conventional microemulsions.

Current State of Research

In our previous work, we have developed the fundamental experimental protocols as well as theoretical framework for the investigation of genome microemulsification in zebrafish cells. In the current, initial phase of the project, we are applying and expanding the existent experimental protocols to the in vitro induction of the zebrafish Nodal pathway. Also, we are expanding the theoretical framework to account for regulatory aspects. Each of these branches of the project is carried out by a doctoral trainee. Both trainees and overall research groups are working in close coordination to align experimental and theoretical work.

The Hilbert lab explores three-dimensional (3D) organization as the foundation of effective information processing in dense DNA suspensions. In particular, we study the cell nucleus as a highly evolved, DNA-based information processing system. In our work, we visualize the inner workings of the nucleus with live and super-resolution microscopy. We translate our observations into physical principles and information processing strategies by means of physical models and computer simulations. Ultimately, we hope to contribute to cell-embedded DNA computing, and the predictive design of DNA-based hardware.

Karlsruhe Institute of Technology