Abstract
Competence is a transiently differentiated state that certain bacterial cells reach when faced with a stressful environment. Entrance into competence can be attributed to the excitability of the dynamics governing the genetic circuit that regulates this cellular behavior. Like many biological behaviors, entrance into competence is a stochastic event. In this case cellular noise is responsible for driving the cell from a vegetative state into competence and back. In this work we present a novel numerical method for the analysis of stochastic biochemical events and use it to study the excitable dynamics responsible for competence in Bacillus subtilis. Starting with a Finite State Projection (FSP) solution of the chemical master equation (CME), we develop efficient numerical tools for accurately computing competence probability. Additionally, we propose a new approach for the sensitivity analysis of stochastic events and utilize it to elucidate the robustness properties of the competence regulatory genetic circuit. We also propose and implement a numerical method to calculate the expected time it takes a cell to return from competence. Although this study is focused on an example of cell-differentiation in Bacillus subtilis, our approach can be applied to a wide range of stochastic phenomena in biological systems.
Highlights
Competence is the ability of a cell, usually a bacterium, to bind and internalize transforming exogenous DNA
We studied the competence regulatory genetic circuit, our approach can be applied to a variety of stochastic events in biological systems
We applied the recently developed Finite State Projection (FSP) method to the reduced model and computed the probability of competence, where competence was defined in terms of a trajectory leaving a pre-defined region of the state space
Summary
Competence is the ability of a cell, usually a bacterium, to bind and internalize transforming exogenous DNA. The few cells that enter competence express a high concentration of the key regulator ComK, which activates hundreds of genes, including the genes encoding the DNA-uptake and recombination systems [5,6,7]. Auto-activation of the regulator ComK is responsible for the bistable response in competence development. The main idea here is to aggregate regions of the state space over which specie evolve into absorbing states This technique is useful in analytically computing the distribution of the first passage time, by providing a way to deal with the infinite dimension of the state space over which the system evolves.
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call