Fiorillo, Luca (2021) Polymer-physics modeling to explore single-cell DNA architecture and characterize experimental methods. [Tesi di dottorato]

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Abstract

The comprehension of the spatial organization of chromosomes in mammal cells is a major challenge for contemporary biophysics, as it is connected with the functionality of the genome. For that reason, sophisticated technologies have been designed to explore the chromosomal architectures, while polymer-physics models have been proposed to make sense of the experimental observations and to identify the molecular mechanisms driving the folding of DNA. Here, we present a polymer-physics model which can explain the conformations of DNA observed in human cells, based on the phase-separation mechanism of classical polymers and on the corresponding thermodynamic degeneracy of states. Additionally, we show that model polymer structures of real chromosomal regions can be used to benchmark, computationally, the performances of different experimental technologies able to capture the architecture of chromosomes (Hi-C, GAM and SPRITE). We will illustrate that such approach allows to quantitatively compare the experimental technologies and, so, define the optimal experimental setup for various possible conditions.

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