This paper holds personal significance for me, as it was my first foray into biomolecular phase separation and DNA self-assembly. I am continuing work on reaction-condensation mechanisms in my new independent group at @unimainz.bsky.social. Stay tuned for more!

Read the full paper here: doi.org/10.1039/D5SM...
Huge thanks to @oasaleh.bsky.social, Gabi Abraham, and the Keck Foundation for their support on work that bridged into many new areas for me.

Such feedback loops could underlie how cells control condensates, or how synthetic systems might be built to compute or regulate via phase transitions.

This work shows how biochemistry (transcription) and materials (phase separation) are interconnected:
- The reaction controls the material state (condensed liquid droplets).
- The material state controls the reaction.

We then engineered negative feedback: the formation of droplets activates condensation, but the droplets repress transcription by sequestering parts of the transcription machinery (template DNA vs RNAP).

A mesoscale “activator/repressor” network.

We found that droplet formation through this transcription-driven route shows: 1) a substantial delay before droplets appear. 2) a non-linear response of droplet volume to RNA production kinetics.

We built a minimal model system: DNA nanostars (self-assembling particles) that only form droplets when a single-stranded RNA linker is present. In vitro transcription reaction (using T7 RNAP) that produces RNA linkers in situ.

It has been shown that transcribed genes participate in liquid-liquid phase separation (LLPS) and that LLPS can condense around regions of the genome, regulating transcription. We wanted to ask: What physical mechanisms are responsible for transcription-condensation coupling?

Lots to learn about DNA (and otherwise) in Mainz, looking forward to your visit!