# Quantitative Aspect of Bacillus subtilis σB Regulatory Network on a Proteome Level—A Computational Simulation

## TL;DR

This paper uses computational modeling to study how the σB regulatory network in Bacillus subtilis functions under stress conditions.

## Contribution

A novel computational model of the σB regulatory network is developed and validated using proteomic data.

## Key findings

- The model simulates the dynamics of σB and its regulatory components using differential equations.
- Proteomic and transcriptomic datasets yield consistent simulation results despite lack of correlation in time series.
- Phosphatases RsbU and RsbP play a key role in transmitting environmental signals in the network.

## Abstract

Bacillus subtilis is a model organism used to study molecular processes in Gram-positive bacteria. Sigma factor B (σB, SigB) is a major regulator of gene expression in response to various stresses. SigB itself is controlled by a network involving several other factors. In this paper, I focused on computational modeling of their interactions and analyzed how these interactions influence the production of SigB and other components of the network. Understanding the detailed functioning of such a network and the concept of its analysis helps to comprehend molecular processes occurring in the cell.

Bacillus subtilis is a model organism used to study molecular processes in Gram-positive bacteria. Sigma factor B, which associates with RNA polymerase, is one of the transcriptional regulators involved in the cell’s response to environmental stress. Experiments have proven that the amounts of free σB (SigB) are controlled by a system of anti- (RsbW) and anti-anti-sigma (RsbV) factors expressed from the same operon as SigB. Moreover, the phosphorylation state of RsbV is controlled by phosphatases RsbP and RsbU, which directly dephosphorylate RsbV. A set of chemical equations describing the network controlling the levels of free SigB was converted to a set of differential equations quantifying the dynamics of the network. The solution of these equations allowed the simulation of the kinetic behavior of the network and its components under real conditions reflected in the time series of protein expression. In this study, the time series of protein expression measured by mass spectrometry were utilized to investigate the role of phosphatases RsbU/RsbP in transmitting the environmental signal. Additionally, the influence of kinetic constants and the amounts of other network components on the functioning of the network was investigated. A comparison with the same simulation performed using a transcriptomic dataset showed that while the time series between the proteomic and transcriptomic datasets are not correlated, the results are the same. This indicates that when modeling is performed within one dataset, it does not matter whether the data come from the mRNA or protein level. In summary, the computational results based on experimental data provide a quantitative insight into the functioning of the SigB-dependent circuit and offer a template for the quantitative study of similar systems.