An Accelerated Biochemical Brownian Dynamics Code Released
Research Groups
This page lists some of the projects running in the E-Cell Project. Some of them makes use of E-Cell System for modeling and simulation, and some others develop the software, tools and methods for the project. See also Community page.
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Mitochondrion
Our goal is to understand and control dynamics of mitochondrial metabolism through computer simulation in a whole organelle scale. For this purpose, we constructed a mitochondrial model which includes the respiratory chain, the TCA cycle, the fatty acid beta-oxidation, and the metabolite transport system at the inner-membrane. Currently, dynamic behaviors of the model is examined with emphasis on pathological application.
(Katsuyuki Yugi) -
E-Neuron
The E-Neuron project aims at reproducing neural nerve behavior at a molecular level using kinetic equations. Using the concept of "systems biology" as our base theory, our simulation approach of "systems molecular neuroscience" is one where the equation system and the range of each parameter are the key values which causes a behavior, rather than the specific value of each parameter. It is therefore necessary to elucidate the "parameter space of a behavior" for our model. Our recent works include simulation of nerve growth cone signal transduction and synaptic plasticity.
(Shinichi Kikuchi) -
E2coli
An energy metabolism model of Escherichia coli was constructed. The metabolism is represented as a hybrid model which combines a quantitative kinetics-based approach and qualitative stoichiometric approach. Central pathways of energy metabolism are represented as a kinetics based model. Metabolite concentrations are measured using Capillary Electrophoresis and Mass Spectrometer (CE/MS).We plan to include a gene expression model to express catabolite repression into the energy metabolism model. The simulation result will be compared with experimental data using isotope labeled glucose.
(Kenta Hashimoto) -
e-Rice
The complete genomic sequence of rice has been elucidated and its metabolism thoroughly researched, making rice an ideal prospect for modeling and simulation. As a basis for the in silico rice modeling project, e-Rice, the preliminary goal is to develop a model for simulating plant cell primary metabolism using E-CELL Simulation Environment.
(Nobuyoshi Ishii, Yoichi Nakayama) -
Erythrocyte
A steady state computer model of the human erythrocyte has been constructed with three major metabolic pathways, glycolysis, the pentose phosphate pathway, nucleotide metabolism, and also ion transport systems. Simulation experiments of Glucose-6-phosphate dehydrogenase (G6PD) deficiency have been carried out using the model. We are currently expanding the model to include not only metabolic pathways, but also the following functions for model robustness and tolerance: pH dependence of enzymes, osmotic balance, electroneutrality, and oxygen and carbon dioxide transportation by hemoglobin. Hybrid stoichiometric and kinetic modeling mothods are being applied (Yugi. K. and Nakayama. Y. et al.). Automated tools for transforming kinetic equations into S-system and GMA forms have been developed for calculating steady-state concentration of intermediates.
(Ayako Kinoshita, Yoichi Nakayama) -
Cell Signaling
My current research has two main threads: (i) implementing a stochastic module in the E-Cell Simulation Environment Version 3 , and (ii) modelling the bacterial chemotaxis signalling pathway. In (i), I am implementing the Stoch Sim algorithm within the E-Cell environment. This algorithm is similar but not equivalent to another stochastic algorithm for simulating chemical kinetics developed by Gillespie, and has properties that are particularly desirable for simulating cell signalling pathways. In (ii), I am extending my thesis work on modelling the bacterial chemotaxis receptor complex, in which I investigated the properties of a hypothetical spatial interaction between membrane receptors that could explain the high gain in the chemotaxis pathway. Because of its simplicity, this pathway is an ideal system for developing both modelling and experimental methods that can be applied to a wide variety of cell signalling systems.
(Tom Shimizu)
I am currently working on making model catalogue of bacterial chemotaxis using E-Cell platform.(1)The most simple model which can represent perfect adaptation (2) More detailed model constructed by Mello and Tu (3)The same model of (2) in which Gillespie algorithm is used in simulation.
(Yuri Matsuzaki) -
Circadian rhythm
A gene regulatory network and signaling pathway of circadian rhythm in Synechococcus sp. PCC7942 was estimated. It is widely known that there is a problem in exploring a broad parameter space of biosystems, and the problem is difficult to solve by simply using genetic algorithm (GA). In this work, the activation energy for each protein-protein interaction is used to limit the searching space. We used the Smoluchowsky equation for representing the activation energy in our computer model, and explored parameters which induce oscillations.
(Fumihiko Miyoshi, Yoichi Nakayama) -
Diabetes
Diabetes arises from short secretion or action failure of insulin. The population of diabetics is increasing year after year. Recent works have elucidated the molecular mechanism of diabetes in detail, but the majority of these investigations is targeted at hereditary diabetes - a minority of diabetes. In addition to genetic causes, the pathogenesis of diabetes caused by environmental factors such as life habits remains unclear. Another characteristic of diabetes pathogenesis is that it involves multible organisms: pancreas, liver, skeletal muscle, and adipose tissue. Our current goal is to construct a multi-organ diabetes model using the E-Cell Simulation Environment.
(Atsuko Sano, Yasuhiro Naito) -
Mathematical Analysis
Simulation using E-CELL Simulation Environment often requires kinetic data of biochemical reactions. However it is generally difficult to obtain them only from literature. One solution is to measure values directly using wet experiments. Though the "wet-approach" is currently being done in IAB, another solution, the "dry-approach", is also required to estimate parameters computationally from limited data. The mathematical analysis group aims to develop novel parameter estimation systems. The group is currently developing methods for metabolic control analysis, mebolic flux analysis and flux balance analysis, and also the application of contorl theory to cell simulation.
(Shinichi Kikuchi) -
Other E-Cell Modeling Projects
- Myocardial Cell
