Laboratoire de Physique Théorique

de la Matière Condensée

Scolari Vittore (Institut Curie)

Forces shaping chromatin in the nucleus

The physics of genome dynamics requires innovative out-of-equilibrium approaches because the cell nucleus, from the most basic chemical reactions to evolutionary timescales of billions of years, strives to counteract disorder in order to be healthy, consuming energy, being alive. My objective is to develop a physical theory able to describe intranuclear dynamics, with the ambition of reaching a quantitative understanding of the two essential processes of gene regulation and DNA recombination. In particular, I investigate: (i) how 3D chromosome conformation is shaped by specific biological processes. Particularly loop extrusion and the formation of foci – or phases – for heterochromatin and transcription, and (ii) the fundamental implications of thee mechanisms on control and reliability of the biological processes of transcriptional induction, gene silencing, and evolution. In this talk I will present my original approach to simulate loop extrusion, an active process central in regulating the shape of chromatin in vivo. The “gold standard” currently uses molecular dynamics simulations: while very flexible, this limits our possibility (i) to explore the parameter space in an efficient manner and (ii) to dissect the observed effects under the lenses of a coherent analytical theory. I will show my original approach that exploits the analytical solution of the Einstein-Smoluchowski equation for the Rouse model affected by the action of extruders simulated in 1D. The resulting probability distributions highlight the hallmarks of the out-of-equilibrium processes on chromatin conformation observed in vivo by experiments. Finally, this approach permits the definition of the Gibbs entropy of chromosome conformation. I will show how the application of this concept to simplified toy-models increases our analytical understanding of the loop extrusion process. Finally, I will present my future scientific plans.