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The bacterial nucleoid: from statistical physics models to synthetic prokaryotic chromosome

Research project selected under the 2021 call for proposals

Principal Investigator : Manoel MANGHI

Involved Teams :

  • LPT / PhysStat
  • IPBS
  • LMGM

Type of project : Disruptive Project

Date (start/end) : 2021 – 2024

Sketch of the DNA surrounded by crowders in the Tethered Particle Motion experiment geometry: DNA is in black, grafted to the substrate (gray) and to the tracked particle (yellow). Non-binding crowders are in blue, simply-binding proteins in red (here bending DNA as HU), multiply-binding proteins (or cations) in green, bridging non-adjacent DNA segments.

Phase separation of cellular material into mesoscopic or macroscopic liquid-like droplets has recently emerged as a fundamental organizing principle in prokaryotic cells, notably of their genetic material. With the ultimate goal to rationalize the different physical theories describing phase separation in the bacterial nucleoid, and its biological implications, we aim in this project at establishing phase diagrams of model systems constituted of DNA, seen as a charged semiflexible polymer, evolving in a ionic solvent enriched in crowders (proteins, ribosomes, small nucleic acids) as well as proteins directly interacting with DNA. The project relies on the combined use of analytical and numerical tools that will rely on the methods of statistical mechanics, both in equilibrium and out of equilibrium. To test our theoretical approaches, in vitro experiments will be conduct in Toulouse (IPBS and LMGM) that rely on a high-throughput single-molecule assay, the tethered particle motion technique parallelized on a DNA chip.