PHD Defense - Arthur Genthon - 14/10/2022 - Fluctuations in cell lineages and population trees: a thermodynamic perspective

Arthur Genthon’s PhD Defense will take place on:
October 14th at 3pm
Holweck amphitheater
ESPCI
10 rue Vauquelin, 75005 Paris

Fluctuations in cell lineages and population trees: a thermodynamic perspective

Experiments on growing cells can be carried out either in bulk or in confined geometries. How should the population trees be sampled in each setup? Are there statistical biases between them? How to quantify natural selection in these trees? These are the main questions we address in this thesis.

In a first part, we study the statistical bias between the single-lineage and population levels, which has similarities with fluctuation theorems in stochastic thermodynamics. To do so, we develop a theoretical framework based on lineage histories within population trees. First, this bias informs on the strength of selection, that quantifies the correlations between the value of a cell trait and the reproductive success of the lineage. This selection results from the variability of lineages in the population, which we analyze using linear response theory.

We also extend our framework to allow situations where lineages end before the end of the experiment, due to cell death or dilution. We show how dead lineages should be taken into account in the statistics, and how death impacts the phenotypic variability and therefore the strength of selection. Second, we show how single-lineage data can be used to infer population-level quantities like the population growth rate, also called Malthus parameter. Focusing on size-regulated populations, we derive steady-state cell size distributions for single-lineage experiments, that can also be used to infer cell cycle parameters such as the single cell elongation rate and the asymmetry of division.

In a second independent part, we propose a thermodynamic description of cell growth and division using simple coarse-grained models of cell size control. This question is important to understand how cell colonies are constrained by thermodynamics. Using a decomposition of cell division in two sub-processes: branching (creation of an identical new cell), and resetting (restart of the properties of the two cells), we derive the first and second laws of thermodynamics for a colony of cells, and identify the contribution of each process to the change in average energy and Shannon entropy. This allows us to understand how the distributions of age and size are affected by cell division from an information-theoretic point of view.