Research

Replication is a hallmark of the living world, from DNA to cells and organisms. To copy information correctly, fuel consumption is necessary, which drives the system out-of-equilibrium and generates dissipation. We study how thermodynamics constrains the accuracy and efficiency of replication, both for copolymer copying (replication, transcription, translation) and for cell division which we model as a combination of branching and resetting. Key results include the discovery of sharp phase transitions between populations of random and accurate polymer copies, and a definition of the efficiency of cell division.

The bio-molecular processes underlying the cell cycle are highly stochastic, which generates great variability between genetically-identical cells. To compensate for these fluctuations, cells need mechanisms to regulate their sizes (sizer, adder, ...). We study the interplay between cell-to-cell variability, size control and population growth. We obtain theoretical predictions on the role of variability and size control in population growth; on cell size distribution, from which parameters of the cell cycle can be inferred by fitting experimental data; and on the bias between size distributions (and size control mechanisms) at the levels of population versus single lineage (mother machine).

Quantifying fitness, selection and survival is a fundamental step in any description of evolution. However, previous definitions of these notions often rely on specific dynamical models. Instead, we use different samplings of the lineages in population trees of dividing organisms, which capture the bias between the population and the single cell levels, to obtain a model-free description of evolution. The results following from this approach are interpreted within the frameworks of stochastic thermodynamics and linear response theory, and provide universal constraints on growth, fitness, selection and survival. Although our research is framed for cell colonies, we hope to find applications in species/gene trees.

We study the melting of a defect basepair and its neighbours in an otherwise homogeneous DNA (only one type of basepair). The defect locally modifies the binding (Watson-Crick) and stacking (nearest neighbors) energies, as caused by basepair mismatches or fluorescent labels attached to the DNA, for example. The analytical solution informs on the scope of the perturbation induced by the defect and on the nature of the melting phase transition.