Topic 3

13:30-13:35: Introduction by coordinator

13:35-14:35: Sanjay Jain "The origin of balanced growth, exponential trajectories and size variation in bacterial cells"

14:35-14:50: Break

14:50-15:50: David Lacoste "Inhibition of bacterial growth by antibiotics: a simple view"

15:50-16:00: Break

16:00-16:30: Atsushi Kamimura "Chemical thermodynamics for growing systems"

16:30-17:30: Informal talks & general discussion

18:00-21:00: Dinner (taxi leave at 18:00 from Lab5 Parking Lot)

The origin of balanced growth, exponential trajectories and size variation in bacterial cells

Speaker: Sanjay Jain

The simplest known cells, bacteria, exhibit some fascinating quantitative regularities at the system level whose origin is not quite understood. The talk will describe three such properties of single cells in steady state cultures: (i) the balanced growth of thousands of intracellular chemicals between birth and division of the cell, (ii) the exponential growth of cell size and intracellular molecular populations in many bacteria, and (iii) a characteristic cell-to-cell variation of size and interdivision time between genetically identical cells in the same medium. We will discuss why these properties are surprising. Possible explanations will be given. (i) and (ii) can be explained by the homogeneous degree one character of the nonlinear functions that describe chemical kinetics in expanding containers of a certain kind, and (iii) by the existence of a time keeper molecule in the cell whose population crossing a certain threshold triggers cell division.

Inhibition of bacterial growth by antibiotics: a simple view

Speaker: David Lacoste

Growth in bacterial populations generally depends on the environment (availability and quality of nutrients, presence of a toxic inhibitor, product inhibition..). Here, we build a simple model to describe the action of a bacteriostatic antibiotic, assuming that this drug inhibits essential autocatalytic cycles involved in the cell metabolism. The model recovers known growth laws, can describe various types of antibiotics and confirms the existence of two distinct regimes of growth-dependent susceptibility, previously identified only for ribosome targeting antibiotics. Interestingly, below a certain threshold in terms of antibiotic concentration, a coexistence between two values of the growth rate is possible, which has also been observed experimentally. If time permits, I will discuss another project about the response of yeast cell populations to acid stress.

Chemical thermodynamics for growing systems

Speaker: Atsushi Kamimura

Protocellular compartments have commonly been considered as model systems for understanding the origins and evolutions of early cells, as well as designing encapsulated reactors for biotechnology. As a prototypical setup, we generally consider open chemical reaction systems (CRSs), wherein autocatalytic chemical reactions are encapsulated within a volume, and the volume  changes in conjunction with the reactions. The thermodynamics of such CRSs is crucial for identifying the physical conditions required for their growth.

In this talk, we introduce a thermodynamic theory for growing CRSs. It provides environmental conditions to determine the fate of the CRSs, whether they will grow, shrink, or reach equilibrium. We also identify thermodynamic constraints: one that restricts the possible states of the CRSs and another that further limits the region where a nonequilibrium steady growing state can exist. We also introduce stoichiometric constraints, where the changes in the number of chemicals are constrained according to the stoichiometry of the reactions. Such constraints are typically imposed by the topological features of cellular metabolic networks.  As a result, the possible states of the systems are further restricted depending on the initial conditions of the system. These results are derived from general thermodynamic considerations based solely on the second law of thermodynamics, emphasizing the significant influence of the variable volumes of the system on the reaction dynamics in the growing states.