Laboratoire Charles Coulomb UMR 5221 CNRS/UM2 (L2C)

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Master project in theoretical physics - Sensing DNA supercoiling in vivo bycombining polymer physics and molecular biology

par Christelle EVE - publié le

Context : In bacteria, DNA is stored as ring molecules displaying supercoiling. Negative supercoiling is essential for DNA compaction in cells, and many essential biological processes such as replication and transcription. The homeostasis of the DNA supercoiling, is namely mediated by topoisomerases. Current experimental techniques to probe supercoiling are restricted to small DNA molecules, namely plasmids up to 12 kb. However, for larger plasmids and for chromosomes, no such measurements of the supercoiling level could be been performed.

We have recently shown [1] that we can use results of experiments of molecular biology obtained in vivo in E. coli to measure supercoiling. We have namely compared the experimental data with Monte Carlo simulations of a polymer with supercoiling.

Goal : The goal of this project is to model bacterial DNA with a supercoiled polymer. The student will use both analytical method of mathematical physics and numerical simulation to decipher the properties of a polymer with a specific topology. The student will subsequently use these results to analyze the experimental data obtained with the genome of Vibrio cholerae, in order to estimate the physical properties of bacterial DNA (persistence length and supercoiling). This study will be essential to justify our proof of concept in [1].

Collaborations : The student will be encourage to interact with collaborators, namely Ivan Junier (TIMC-IMAG, Univ.-Grenoble-Alpes) for numerical simulations and Jean-Yves Bouet (LMGM, Univ. Paul Sabatier, Toulouse) for the experiments in microbiology.

Profile of the student : Master 2 (or possibly Master 1).
Place
 : Laboratoire Charles Coulomb, Montpellier, France.
Duration : 3 months, funded. Possibility of extension on mutual agreement.

Skills : interest for numercial and mathematical physics applied to biology (languages Python, C, C++).

[1] Walter* J.-C., Lepage T., Dorignac J., Geniet F., Parmeggiani A., Palmeri J., Parmeggiani A., Bouet J.-Y. et Junier* I. Models of supercoiled DNA interacting with an anchored cluster of proteins : towards a quantitative estimation of chromosomal DNA supercoiling [arXiv:2002.00111].

For application and any question, please contact :
Jean-Charles WALTER


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