Yuri Matsuzaki

E-CELL: software environment for whole-cell simulation.

MOTIVATION Genome sequencing projects and further systematic functional analyses of complete gene sets are producing an unprecedented mass of molecular information for a wide range of model organisms. This provides us with a detailed account of the cell with which we may begin to build models for simulating intracellular molecular processes to predict the dynamic behavior of living cells. Previous work in biochemical and genetic simulation has isolated well-characterized pathways for detailed analysis, but methods for building integrative models of the cell that incorporate gene regulation, metabolism and signaling have not been established. We, therefore, were motivated to develop a software environment for building such integrative models based on gene sets, and running simulations to conduct experiments in silico. RESULTS E-CELL, a modeling and simulation environment for biochemical and genetic processes, has been developed. The E-CELL system allows a user to define functions of proteins, protein-protein interactions, protein-DNA interactions, regulation of gene expression and other features of cellular metabolism, as a set of reaction rules. E-CELL simulates cell behavior by numerically integrating the differential equations described implicitly in these reaction rules. The user can observe, through a computer display, dynamic changes in concentrations of proteins, protein complexes and other chemical compounds in the cell. Using this software, we constructed a model of a hypothetical cell with only 127 genes sufficient for transcription, translation, energy production and phospholipid synthesis. Most of the genes are taken from Mycoplasma genitalium, the organism having the smallest known chromosome, whose complete 580 kb genome sequence was determined at TIGR in 1995. We discuss future applications of the E-CELL system with special respect to genome engineering. AVAILABILITY The E-CELL software is available upon request. SUPPLEMENTARY INFORMATION The complete list of rules of the developed cell model with kinetic parameters can be obtained via our web site at: http://e-cell.org/.

The E-CELL project: Towards integrative simulation of cellular processes

The E-CELL project was launched in 1996 at Keio University in order to model and simulate various cellular processes with the ultimate goal of simulating the cell as a whole. The first version of the E-CELL simulation system, which is a generic software package for cell modeling, was completed in 1997. The E-CELL system enables us to model not only metabolic pathways but also other higher-order cellular processes such as protein synthesis and membrane transport within the same framework. These various processes can then be integrated into a single simulation model.Using the E-CELL system, we have successfully constructed a virtual cell with 127 genes sufficient for “self-support”. The gene set was selected from the genome of Mycoplasma genitalium the organism having the smallest known genome. The set includes genes for transcription, translation, the glycolysis pathway for energy production, membrane transport, and the phospholipid biosynthesis pathway for membrane structure.The E-CELL system has been made available for beta testing from our website (http: //www.e-cell.org).

Robust effects of Tsr-CheBp and CheA-CheYp affinity in bacterial chemotaxis

OBJECTIVE Cell motility and chemotaxis play a role in the virulence of pathogenic bacteria, such as escape from host immune responses. Escherichia coli chemotaxis provides a well-characterized model system for the bacterial chemotaxis network. Two features of E. coli chemotaxis include signal amplification and robustly accurate adaptation. Recent simulation studies with models considering the effects of other receptors have suggested possible mechanisms for signal amplification. Although precise adaptation to aspartate has been explained by conventional kinetic models, the adaptation behavior of models incorporating the effects of other receptors remains unclear. METHODS We concentrated on how receptor crosstalk affects minimization of adaptation error and compared models in which the contribution of other receptors varied. RESULTS We demonstrated that the model is adaptable to attractant concentrations ranging from 0.1microM to 10mM with a decreased error rate (from 8% to 2%) when the kinetic constant of CheA and phosphorylated CheY dissociation is increased. CONCLUSION The results suggest that accurate adaptation is maintained through control of both the interaction of cytoplasmic Che proteins and the activity of the receptor complex.

The E-CELL project: towards integrative simulation of cellular processes

The E-CELL project was launched in 1996 at Keio University in order to model and simulate various cellular processes with the ultimate goal of simulating the cell as a whole. The first version of the E-CELL simulation system, which is a generic software package for cell modeling, was completed in 1997. The E-CELL system enables us to model not only metabolic pathways but also other higher-order cellular processes such as protein synthesis and membrane transport within the same framework. These various processes can then be integrated into a single simulation model.

A Model Library of Bacterial Chemotaxis on E-Cell System

Bacterial organisms like Escherichia coli have developed mechanisms to detect and direct cell movement toward substrate when starved. Such behavior is known as chemotaxis (15 for recent review).