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Anjan Roy

Publications and source records attributed to Anjan Roy.

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Single-cell-level distributions and relationships can differentiate cell-division and growth models

Complex interactions among regulatory molecules determine the rules underlying cell growth and division in microbial cells. While the governing molecular network may not always be obvious, it is well known that correlations among certain physiological quantities measured in experiments, such as birth-size, division-size, division-time, and division-added-size, can differentiate among various cell-division models, such as Timer, Sizer, and Adder. Here we show that, apart from these correlations, which we extend for the case of stochastic single-cell growth and stochastic asymmetric partitioning, probability distributions of these quantities and statistical relationships between them can also be used to differentiate between these division models. Interestingly, we show that these quantities can not only differentiate the division models, but also distinguish among the single-cell growth paradigms, such as linear and exponential growth. We then demonstrate this differentiability among various division and growth models by comparing our analytical results with published experimental data. We further show that these results remain valid even when the growth rate of a cell is correlated with the growth rate of cells from previous generations in the lineage.

cond-mat.stat-mech

On distinguishability among cell-division models based on population and single-cell-level distributions

It is well known that the different cell-division models, such as Timer, Sizer, and Adder, can be distinguished based on the correlations between different single-cell-level quantities such as birth-size, division-time, division-size, and division-added-size. Here, we show that other statistical properties of these quantities can also be used to distinguish between them. Additionally, the statistical relationships and different correlation patterns can also differentiate between the different types of single-cell growth, such as linear and exponential. Further, we demonstrate that various population-level distributions, such as age, size, and added-size distributions, are indistinguishable across different models of cell division despite them having different division rules and correlation patterns. Moreover, this indistinguishability is robust to stochasticity in growth rate and holds for both exponential and linear growth. Finally, we show that our theoretical predictions are corroborated by simulations and supported by existing single-cell experimental data.

cond-mat.stat-mech

Slowing translation to avoid ribosome population extinction and maintain stable allocation at slow growth rates

To double the cellular population of ribosomes, a fraction of the active ribosomes is allocated to synthesize ribosomal proteins. Subsequently, these ribosomal proteins enter the ribosome self-assembly process, synthesizing new ribosomes and forming the well-known ribosome autocatalytic subcycle. Neglecting ribosome lifetime and the duration of the self-assembly process, the doubling rate of all cellular biomass can be equated with the fraction of ribosomes allocated to synthesize an essential ribosomal protein times its synthesis rate. However, ribosomes have a finite lifetime, and the assembly process has a finite duration. Furthermore, the number of ribosomes is known to decrease with slow growth rates. The finite lifetime of ribosomes and the decline in their numbers present a challenge in sustaining slow growth solely through controlling the allocation of ribosomes to synthesize more ribosomal proteins. When the number of ribosomes allocated per mRNA of an essential ribosomal protein is approximately one, the resulting fluctuations in the production rate of new ribosomes increase, causing a potential risk that the actual production rate will fall below the ribosome death rate. Thus, in this regime, a significant risk of extinction of the ribosome population emerges. To mitigate this risk, we suggest that the ribosome translation speed is used as an alternative control parameter, which facilitates the maintenance of slow growth rates with a larger ribosome pool. We clarify the observed reduction in translation speed at harsh environments in E. coli and C. Glutamicum, explore other mitigation strategies, and suggest additional falsifiable predictions of our model.

q-bio.OT

The rise and fall of hubs in Self-Organized Critical learning networks

Information processing networks are the result of local rewiring rules. In many instances, such rules promote links where the activity at the two end nodes is positively correlated. The conceptual problem we address is what network architecture prevails under such rules and how does the resulting network, in turn, constrain the dynamics. We focus on a simple toy model that captures the interplay between link self-reinforcement and a Self-Organised Critical dynamics in a simple way. Our main finding is that, under these conditions, a core of densely connected nodes forms spontaneously. Moreover, we show that the appearance of such clustered state can be dynamically regulated by a fatigue mechanism, eventually giving rise to non-trivial avalanche exponents.

cond-mat.stat-mech

Transcription-translation machinery -- an autocatalytic network coupling all cellular cycles and generating a plethora of growth laws

Recently discovered simple quantitative relations, known as bacterial growth laws, hint on the existence of simple underlying principles at the heart of bacterial growth. In this work, we provide a unifying picture on how these known relations, as well as new relations that we derive, stems from a universal autocatalytic network common to all bacteria, facilitating balanced exponential growth of individual cells. We show that the core of the cellular autocatalytic network is the transcription -- translation machinery -- in itself an autocatalytic network comprising several coupled autocatalytic cycles, including the ribosome, RNA polymerase, and tRNA charging cycles. We derive two types of growth laws per autocatalytic cycle, one relating growth rate to the relative fraction of the catalyst and its catalysis rate, and the other relating growth rate to all the time scales in the cycle. The structure of the autocatalytic network generates numerous regimes in state space, determined by the limiting components, while the number of growth laws can be much smaller. We also derive a growth law that accounts for the RNA polymerase autocatalytic cycle, which we use to explain how growth rate depends on the inducible expression of the rpoB and rpoC genes, which code for the RpoB and C protein subunits of RNA polymerase, and how the concentration of rifampicin, which targets RNA polymerase, affects growth rate without changing the RNA-to-protein ratio. We derive growth laws for tRNA synthesis and charging, and predict how growth rate depends on temperature, perturbation to ribosome assembly, and membrane synthesis.

q-bio.MN

Energy current cumulants in one-dimensional systems in equilibrium

Recently a remarkable connection has been proposed between the fluctuating hydrodynamic equations of a one-dimensional fluid and the Kardar-Parizi-Zhang (KPZ) equation for interface growth. This connection has been used to relate equilibrium correlation functions of the fluid to KPZ correlation functions. Here we use this connection to compute the exact cumulant generating function for energy current in the fluid system. This leads to exact expressions for all cumulants and in particular to universal results for certain combinations of the cumulants. As examples, we consider two different systems which are expected to be in different universality classes, namely a hard particle gas with Hamiltonian dynamics and a harmonic chain with momentum conserving stochastic dynamics. Simulations provide excellent confirmation of our theory.

cond-mat.stat-mech

Tagged particle diffusion in one-dimensional systems with Hamiltonian dynamics - II

We study various temporal correlation functions of a tagged particle in one-dimensional systems of interacting point particles evolving with Hamiltonian dynamics. Initial conditions of the particles are chosen from the canonical thermal distribution. The correlation functions are studied in finite systems, and their forms examined at short and long times. Various one-dimensional systems are studied. Results of numerical simulations for the Fermi-Pasta-Ulam chain are qualitatively similar to results for the harmonic chain, and agree unexpectedly well with a simple description in terms of linearized equations for damped fluctuating sound waves. Simulation results for the alternate mass hard particle gas reveal that - in contradiction to our earlier results [1] with smaller system sizes - the diffusion constant slowly converges to a constant value, in a manner consistent with mode coupling theories. Our simulations also show that the behaviour of the Lennard-Jones gas depends on its density. At low densities, it behaves like a hard-particle gas, and at high densities like an anharmonic chain. In all the systems studied, the tagged particle was found to show normal diffusion asymptotically, with convergence times depending on the system under study. Finite size effects show up at time scales larger than sound traversal times, their nature being system-specific.

cond-mat.stat-mech

Tagged particle diffusion in one-dimensional gas with Hamiltonian dynamics

We consider a one-dimensional gas of hard point particles in a finite box that are in thermal equilibrium and evolving under Hamiltonian dynamics. Tagged particle correlation functions of the middle particle are studied. For the special case where all particles have the same mass, we obtain analytic results for the velocity auto-correlation function in the short time diffusive regime and the long time approach to the saturation value when finite-size effects become relevant. In the case where the masses are unequal, numerical simulations indicate sub-diffusive behaviour with mean square displacement of the tagged particle growing as t/ln(t) with time t. Also various correlation functions, involving the velocity and position of the tagged particle, show damped oscillations at long times that are absent for the equal mass case.

cond-mat.stat-mech