title: Construction of a generalized simulator for multi-cellular organisms and its application to SMAD signal transduction.
abstract: In this paper, we report development of a generalized simulation system based on ordinary differential equations for multi-cellular organisms, and results of the analysis on a Smad signal transduction cascade. The simulator implements intra-cellular and extra-cellular molecular processes, such as protein diffusion, ligand-receptor reaction, biochemical reaction, and gene expression. It simulates the spatio-temporal patterning in various biological phenomena for the single and multi-cellular organisms. In order to demonstrate the usefulness of the simulator, we constructed a model of Drosophila's Smad signal transduction, which includes protein diffusion, biochemical reaction and gene expression. The results suggest that the presence of negative feedback mechanism in the Smad pathway functions to improve the frequency response of the cascade against changes in the signaling.
authors.affiliation: Kitano Symbiotic Systems Project, ERATO, Tokyo, Japan. kyoda@symbio.jst.go.jp
authors.forename: K M
authors.initials: KM
authors.lastname: Kyoda
authors.forename: M
authors.initials: M
authors.lastname: Muraki
authors.forename: H
authors.initials: H
authors.lastname: Kitano
mesh_terms: D000818:Animals; D003198:Computer Simulation; D004330:Drosophila / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015870:Gene Expression; D019476:Insect Proteins / Q000378:metabolism; D008954:Models, Biological; D015398:Signal Transduction
chemical_list: D019476:Insect Proteins