PhD defense of  Elham GHOBADPOUR student at TIMC TrEE on wednesday, the 29th of march, at 2pm:
 

« Multiple scale modeling of Bacterial Chromosome. »

Jury :

• Ivan JUNIER, Directeur de recherche, CNRS, Supervisor
• Ralf EVERAERS, Professeur des Universités, École Normale Supérieure de Lyon (ENS-Lyon), Co-Supervisor
• Maria BARBI, Professeure des Universités, Sorbonne Université, Reporter
• Romain KOSZUL, Directeur de recherche, Institut Pasteur, Reporter
• Irina MIHALCESCU, Professeure des Universités, Université Grenoble Alpes, Examiner
• Alexander GROSBERG, Professeur, New York University Department of Physics, Examiner

Keywords

bacterial chromosomes, polymer physics, Multi-scale modelling, Hi-C data, Contact probability, plectonemes

Abstract

Supercoiled DNA often adopts tree-like double-folded branching configurations. In this context, We proposed a framework to generate expected bacterial chromosome structures at multiple scales.
Stage I: A lattice model for the dynamics of randomly branching double-folded ring polymers.
First, We studied an elastic lattice model for tightly double-folded ring polymers, which allows for the spontaneous creation and deletion of side branches coupled to a diffusive mass transport, which is local both in space and on the connectivity graph of the tree. Monte Carlo simulations were performed and studied systems belonging to three different universality classes: ideal double-folded rings without excluded volume interactions, self-avoiding double-folded rings, and double-folded rings in the melt state. The observed static properties are in good agreement with exact results, simulations, and predictions from Flory theory for randomly branching polymers. For example, in the melt state, rings adopt compact configurations and exhibit territorial behaviors. In particular, We show that the emergent dynamics are in excellent agreement with a recent scaling theory. We illustrated the qualitative differences with the familiar reptation dynamics of linear chains.
Stage II: Coarse-grained models of supercoiled DNA at multiple scales.
Second, We built a coarse-grained model of bacterial DNA, which is known to adopt tree-like plectonemic structures due to negative DNA supercoiling. To that end, starting from the first model, We included the possibility of generating long branches, with the average length becoming a free parameter of the model. Considering DNA concentration and cylindrical confinement similar to the in vivo situation, We adjusted this average length parameter to reproduce as well as possible contact properties between chromosomal loci as obtained from high-throughput chromosome conformation capture methods (Hi-C). Soft excluded-volume interactions were also included to deal with the models of the lowest resolutions.
As a result, We obtained various coarse-grained models that are consistent with each other and allow capturing contact properties of multiple bacteria, from 10 kb to 1 Mb scale. In other words, we are able to rationalize from first principles contact properties between bacterial chromosomal loci as measured from high-throughput conformation capture (Hi-C) methods.
References
1. E. Ghobadpour, M. Kolb, M. R. Ejtehadi, and R. Everaers, “Monte Carlo simulation of a lattice model for the dynamics of randomly branching double-folded ring polymers,” Phys. Rev. E, vol. 104, p. 014501, Jul 2021.