Details of a Researcher - Tomita, Masaru

Papers - Tomita, Masaru

Division display 361 - 380 of about 520 ／ All the affair displays >>

Versatile architecture of a bacterial aconitase B and its catalytic performance in the sequential reaction coupled with isocitrate dehydrogenase

Tsuchiya D., Shimizu N., and Tomita M.

BBA - Proteins and Proteomics. 1784 ( 11 ) 1847-56. - 1856 2008

Research paper (scientific journal), Joint Work, ISSN 15709639

Aconitase B (AcnB) and isocitrate dehydrogenase (ICDH) catalyze the sequential reaction in the Krebs cycle. Since each enzyme was characterized as an independent protein in a diluted condition, the catalytic performance within the cellular metabolism remains unclear. In particular, high macromolecular concentration in the cytosol promotes weak interactions, which affects structure and function of the proteins. We found that the two bacterial enzymes exhibit variable catalytic performance of the sequential reaction, depending on the oligomerization state. The small-angle solution X-ray scattering and the chemical crosslinking analyses revealed that not only the two enzymes but also the fusion protein of the two enzymes assume homodimers in solution. Interestingly, the fusion protein maintains the homodimeric architecture of ICDH, but not AcnB. Instead, one of the two monomeric AcnB regions associates with the homodimeric ICDH region. The fusion protein displayed different catalytic performance of the sequential reaction from that observed in the mixture of the AcnB and ICDH proteins in an equimolar ratio. Connecting the two proteins by a flexible linker yielded a locally high concentration to promote the weak protein-protein interaction. The versatile architecture of AcnB may alter the metabolic process involving the Krebs cycle. © 2008 Elsevier B.V. All rights reserved.

Access to Document (DOI)

Aligning LC Peaks by Converting Gradient Retention Times to Retention Index of Peptides in Proteomic Experiments

Shinoda, K., Tomita, M., Ishihama, Y.

Bioinformatics. 24 ( 14 ) 1590-5 - 1595 2008

Research paper (scientific journal), Joint Work, ISSN 13674803

Motivation: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful tool in proteomics studies, but when peptide retention information is used for identification purposes, it remains challenging to compare multiple LC-MS/MS runs or to match observed and predicted retention times, because small changes of LC conditions unavoidably lead to variability in retention times. In addition, non-contiguous retention data obtained with different LC-MS instruments or in different laboratories must be aligned to confirm and utilize rapidly accumulating published proteomics data. Results: We have developed a new alignment method for peptide retention times based on linear solvent strength (LSS) theory. We found that log k0 (logarithm of retention factor for a given organic solvent) in the LSS theory can be utilized as a 'universal' retention index of peptides (RIP) that is independent of LC gradients, and depends solely on the constituents of the mobile phase and the stationary phases. We introduced a machine learning-based scheme to optimize the conversion function of gradient retention times (tg) to log k0. Using the optimized function, tg values obtained with different LC-MS systems can be directly compared with each other on the RIP scale. In an examination of Arabidopsis proteomic data, the vast majority of retention time variability was removed, and five datasets obtained with various LC-MS systems were successfully aligned on the RIP scale. © The Author 2008. Published by Oxford University Press. All rights reserved.

Access to Document (DOI)

Restriction on conjugational transfer of pLS20 in Bacillus subtilis 168

Ohtani, N., Sato, M., Tomita, M. and Itaya, M ,

Biosci. Biotechnol. Biochem. , 72 ( 9 ) 2472-5 - 2475 2008

Research paper (scientific journal), Joint Work, ISSN 09168451

Access to Document (DOI)

Junction ribonuclease: a ribonuclease HII orthologue from Thermus thermophilus HB8 prefers the RNA-DNA junction to the RNA/DNA heteroduplex

Ohtani, N., Tomita, M. and Itaya, M.

Biochem. J. 412 ( 3 ) 517-26 - 526 2008

Research paper (scientific journal), Joint Work, ISSN 02646021

The genome of an extremely thermophilic bacterium, Thermus thermophilus HB8, contains a single ORF (open reading frame) encoding an RNase-HII-like sequence. Despite the presence of significant amino acid sequence identities with RNase (ribonuclease) HII enzymes, the ORF TTHA0198 could not suppress the temperature-sensitive growth defect of an RNase-H-deficient Escherichia coli mutant and the purified recombinant protein could not cleave an RNA strand of an RNA/DNA heteroduplex, suggesting that the TTHA0198 exhibited no RNase H activity both in vivo and in vitro. When oligomeric RNA-DNA/DNAs were used as a mimic substrate for Okazaki fragments, however, the protein cleaved them only at the 5′ side of the last ribonucleotide at the RNA-DNA junction. In fact, the TTHA0198 protein prefers the RNA-DNA junction to the RNA/DNA hybrid. We have referred to this activity as JRNase (junction RNase) activity, which recognizes an RNA-DNA junction of the RNA-DNA/DNA heteroduplex and cleaves it leaving a mono-ribonucleotide at the 5′ terminus of the RNA-DNA junction. E. coli and Deinococcus radiodurans RNases HII also cleaved the RNA-DNA/DNA substrates at the same site with a different metal-ion preference from that for RNase H activity, implying that the enzymes have JRNase activity as well as RNase H activity. The specialization in the JRNase activity of the RNase HII orthologue from T. thermophilus HB8 (Tth-JRNase) suggests that the JRNase activity of RNase HII enzymes might be independent of the RNase H activity. © The Authors.

Access to Document (DOI)

GeNESiS: Gene Network Evolution SImulation Software

Anton Kratz, Masaru Tomita and Arun Krishnan

BMC Bioinformatics 9 541 2008

Research paper (scientific journal), Joint Work

Background: There has been a lot of interest in recent years focusing on the modeling and simulation of Gene Regulatory Networks (GRNs). However, the evolutionary mechanisms that give rise to GRNs in the first place are still largely unknown. In an earlier work, we developed a framework to analyze the effect of objective functions, input types and starting populations on the evolution of GRNs with a specific emphasis on the robustness of evolved GRNs. Results: In this work, we present a parallel software package, GeNESiS for the modeling and simulation of the evolution of gene regulatory networks (GRNs). The software models the process of gene regulation through a combination of finite-state and stochastic models. The evolution of GRNs is then simulated by means of a genetic algorithm with the network connections represented as binary strings. The software allows users to simulate the evolution under varying selective pressures and starting conditions. We believe that the software provides a way for researchers to understand the evolutionary behavior of populations of GRNs. Conclusion: We believe that GeNESiS will serve as a useful tool for scientists interested in understanding the evolution of gene regulatory networks under a range of different conditions and selective pressures. Such modeling efforts can lead to a greater understanding of the network characteristics of GRNs. © 2008 Kratz et al; licensee BioMed Central Ltd.

Access to Document (DOI)

Informatics for Peptide Retention Properties in Proteomic LC-MS

Shinoda, K., Sugimoto, M., Tomita, M. and Ishihama, Y.

Proteomics 8 ( 4 ) 787-98 - 798 2008

Research paper (scientific journal), Joint Work, ISSN 16159853

Retention times in HPLC yield valuable information for the identification of various analytes and the prediction of peptide retention is useful for the identification of peptides/proteins in LC-MS-based proteomics. Informatics methods such as artificial neural networks and support vector machines capable of solving nonlinear problems made possible the accurate modeling of quantitative structure-retention relationships of peptides (including large polymers) up to 5 kDa to which classical linear models cannot be applied, as well as the proteome-wide prediction of peptide retention. Proteome-wide retention prediction and accurate mass-information facilitate the identification of peptides in complex proteomic samples. In this review, we address recent developments in solid informatics methods and their application to peptide-retention properties in 'bottom-up' shotgun proteomics. We also describe future prospects for the standardization and application of retention times. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.

Access to Document (DOI)

Comparison and characterization of proteomes in the three domains of life using 2D correlation analysis

Fujishima K., Komasa M., Kitamura S., Tomita M., Kanai A.

Progress of Theoretical Physics Supplement ( 173 ) 206 - 218 2008

ISSN 03759687

Proteins are a major regulatory component in complex biological systems. Among them, DNA/RNA-binding proteins, the key components of the central dogma of molecular biology, and membrane proteins, which are necessary for both signal transduction and metabolite transport, are suggested to be the most important protein families that arose in the early stage of life. In this study, we computationally analyzed the whole proteome data of six model species to overview the protein diversity in the three domains of life (Bacteria, Archaea and Eukaryota), especially focusing on the above two protein families. To compare the protein distribution among the six model species, we calculated various protein profiles: hydropathy, molecular weight, amino acid composition and periodicity for each protein. We found a domain-specific distribution of the proteome based on 2D correlation analysis of hydropathy and molecular weight. Further, the merged protein distribution of Archaea and other domains revealed many membrane proteins localized in Bacteria-specific regions with a high ratio of hydropathy and many DNA/RNA-binding proteins localized in Eukaryota-specific regions with a low ratio of hydropathy. Since about half of the proteins encoded in the genome are still functionally unknown, we further conducted Support Vector Machine (SVM)-based functional prediction using amino acid composition (CO score) and periodicity (PD score) as feature vectors to predict the overall number of DNA/RNA-binding proteins and membrane proteins in the proteome. Our estimation indicated that two functional categories occupy approximately 60% to 80% of the proteome, and further, the proportion of the two categories varied among the three domains of life, suggesting that the proteome has gone through different selective pressure during evolution.

Access to Document (DOI)

Construction of a Biological Tissue Model Based on a Single-Cell Model: A Computer Simulation of Metabolic Heterogeneity in the Liver Lobule

Ohno, H., Naito, Y., Nakajima, H. and Tomita, M.

Artificial Life 14 ( 1 ) 3-28 - 28 2008

Research paper (scientific journal), Joint Work, ISSN 10645462

An enormous body of information has been obtained by molecular and cellular biology in the last half century, However, even these powerful approaches are not adequate when it comes to higher-level biological structures, such as tissues, organs, and individual organisms, because of the complexities involved. Thus, accumulation of data at the higher levels supports and broadens the context for that obtained on the molecular and cellular levels. Under such auspices, an attempt to clucidate mesoscopic and macroscopic subjects based on plentiful nanoscopic and microscopic data is ot great potential value. On the other hand, fully realistic simulation is impracticable because of the extensive cost entailed and enormous amount of data required. Abstraction and modeling that balance the dual requirements of prediction accuracy and manageable calculation cost are of great importance for systems biology. We have constructed an ammonia metabolism model of the hepatic lobule, a histological component of the liver, based on a single-hepatocyte model that consists of the biochemical kinetics of enzymes and transporters. To bring the calculation cost within reason, the porto-central axis, which is an elemental structure of the lobule, is defined as the systems biological unit of the liver, and is accordingly modeled. A model including both histological structure and position-specific gene expression of major enzymes largely represents the physiological dynamics of the hepatic lobule in nature. In addition, heterogeneous gene expression is suggested to have evolved to optimize the energy efficiency of ammonia detoxificattion at the macroscopic level, implying that approaches like this may elucidate how properties at the molecular and cellular levels, such as regulated gene expression, modify higher-level phenomena of multicellular tissue, organs, and organisms. © 2008 Massachusetts Institute of Technology.

Access to Document (DOI)

Comparative Study of Circadian Oscillatory Network Models of Drosophila

Ogawa, Y., Arakawa, K., Kaizu, K., Miyoshi, F., Nakayama, Y. and Tomita, M.

Artificial Life 14 ( 1 ) 29-48 - 48 2008

Research paper (scientific journal), Joint Work, ISSN 10645462

The circadian clock of Drosophila is a model pathway for research in biological dock mechanisms, both with traditional experimental approaches and with emerging systems biology approaches utilizing mathematical modeling and in silico computer simulation. Dynamic diurnal oscillations are achieved by the complex interaction of components as a system, and mathematical reconstruction his proven to be an invaluable means of understanding such systematic behavior. In this study, we implemented eight published models of the Drosqpbila circadian clock in Systems Biology Markup Language (SBML) for comparative systems biology studies using E-Cell Simulation Environment version 3, to examine the system-level requirements for the clock mechanism to be robust, by calculating the period and amplitude sensitivity coefficients with simulation experiments. While all models were generally robust as determined by the network topology of the oscillatory feedback loop structure, existing models place relatively strong emphasis on transcription regulation, although this is a limitation on robustness. We suggest that more comprehensive modeling including protein phosphorylation, polymerization, and nuclear transport with regard to amplitude sensitivity will be necessary for understanding the light entrainment and temperature compensation of circadian clocks. © 2008 Massachusetts Institute of Technology.

Access to Document (DOI)

Algebraic Method for the Analysis of Signaling Crosstalk

Matsubara, Y., Kikuchi, S., Sugimoto, M., Oka, K. and Tomita, M.

Artificial Life 14 ( 1 ) 81-94 - 94 2008

Research paper (scientific journal), Joint Work, ISSN 10645462

A unified mathematical description that expresses the characteristics of whole systems is necessary for an understanding of signal transduction cascades. In this study we explore an algebraic method, named extreme signaling flow, enhanced from the concept of extreme pathway, to analyze signal transduction systems. This method enables us to represent the long-term potentiation (LTP) and the long-term depression (LTD) of hippocampal neuronal plasticity in an integrated simulation model. The model is validated by comparing the results of redundancy, reaction participation, and in silico knockout analysis with biological knowledge available from the literature. The following properties are assumed in these computational analyses: (1) LTP is fault-tolerant under network modification, (2) protein kinase C and MAPK have numerous routes to LTP induction, (3) calcium-calmodulin kinase II has a few routes to LTP induction, and (4) calcineurin has many routes to LTD induction. These results demonstrate that our approach produces an integrated framework for analyzing properties of large-scale systems with complicated signal transduction. © 2008 Massachusetts Institute of Technology.

Access to Document (DOI)

Automated Phosphoproteome Analysis for Cultured Cancer Cells by Two-Dimensional NanoLC-MS Using a Calcined Titania/C18 Biphasic Column

Imami, K., Sugiyama, N., Kyono, Y., Tomita, M. and Ishihama, Y.

Innovations in Analytical Sciences 24 ( 1 ) 161 - 166 2008

Research paper (scientific journal), Joint Work, ISSN 09106340

We have developed an on-line automated system for phosphoproteome analysis using titania-based phosphopeptide enrichment followed by nanoLC-MS/MS. Titania beads were prepared by calcination of commercial chromatographic titania beads at 800°C to convert the crystalline structure. The obtained rutile-form titania exhibited higher selectivity in phosphopeptide enrichment than commercial titania, even in the absence of a competitive chelating reagent for non-phosphopeptides. For phosphoproteome analysis of human cervical cancer HeLa cells, tryptic digests of the cell extracts were directly injected into this on-line system, and 696 non-redundant phosphopeptides with 671 unambiguously determined phosphorylation sites, derived from 512 phosphoproteins, were successfully identified. This is the first successful application of an on-line automated phosphoproteome analysis system to complex biological samples. 2008 © The Japan Society for Analytical Chemistry.

Access to Document (DOI)

Depiction of metabolome changes in histidine-starved Escherichia coli by CE-TOFMS

Ohashi,Y.,Hirayama,A.,Ishikawa,T.,Nakamura,S.,Shimizu,K.,Ueno,Y.,Tomita,M.and Soga,T.

Mol.BioSyst 4 ( 2 ) 135-147 - 147 2008

Research paper (scientific journal), Joint Work, ISSN 1742206X

Metabolic changes in response to histidine starvation were observed in histidine-auxotrophic Escherichia coli using a capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)-based metabolomics technique. Prior to the analysis, we prepared an E. coli metabolome list of 727 metabolites reported in the literature. An improved method for metabolite extraction was developed, which resulted in higher extraction efficiency in phosphate-rich metabolites, e.g., ATP and GTP. Based on the results, 375 charged, hydrophilic intermediates in primary metabolisms were analysed simultaneously, providing quantitative data of 198 metabolites. We confirmed that the intracellular levels of intermediates in histidine biosynthesis are rapidly accumulated in response to a drop in histidine level under histidine-starved conditions. Simultaneously, disciplined responses were observed in the glycolysis, tricarboxylic acid cycle, and amino acid and nucleotide biosynthesis pathways as regulated by amino acid starvation. © The Royal Society of Chemistry.

Access to Document (DOI)

Evolution of gene regulatory networks:Robustness as an emergent property of evolution

Krishnan,A.,Tomita,M.and Giuliani,A.

Physica A:Statistical Mechanics nad its Applications 387 ( 8-9 ) 2170-2186 - 2186 2008

Research paper (scientific journal), Joint Work, ISSN 03784371

Gene Regulatory Networks (GRNs) have become a major focus of interest in recent years. Although much work has been done in elucidating the transcriptional regulatory network, the underlying mechanisms that have possibly influenced the evolution of these GRNs are still debatable. We have developed a framework to analyze the effect of objective functions, input types and starting populations on the evolution of GRNs with a specific emphasis on the robustness of evolved GRNs. We observed that robustness evolves along with the networks as an emergent property even in the absence of specific selective pressure towards more robust systems. In addition, robustness was independent of the selective pressure, input types or the initial starting populations. We also observed the existence of multiple genotypes giving rise to the same phenotype in accordance with the theoretical view that natural selection operates on phenotypes thereby accommodating variation in the genotype by fixing those changes that are phenotype-neutral. This study gives a proof-of-concept of the fact that robustness is an emergent property of GRNs as well as of the degeneracy of the network topology/function relationship analogous to the sequence/structure problem in proteins. © 2007 Elsevier Ltd. All rights reserved.

Access to Document (DOI)

Reshuffling of the Bacillus subtilis 168 genome by multifold inversion

Kuroki,A.,TOda,T.,Matsui,K.,Uotsu-Tomita,R.,Tomita,M.and Itaya,M.

Journal of Biochemistry 143 ( 1 ) 97-105 - 105 2008

Research paper (scientific journal), Joint Work, ISSN 0021924X

The genome of Bacillus subtilis 168 was modified to yield a genome vector for the cloning of DNA several Mb in size. Unlike contemporary plasmid-based vectors, this 4.2 Mb genome vector requires specific in vivo handling protocols because of its large size. Inversion mutagenesis, a method to modify local genome structure without gain or loss of genes, was applied intensively to the B. subtilis genome; this technique made possible both exchange and translocation of designated regions of the genome. This method not only reshuffles the genome of B. subtilis, but can provide insight into the biologic principles underlying genome plasticity. © 2007 The Japanese Biochemical Society.

Access to Document (DOI)

E. coli metabolomics: Capturing the complexity of a "simple" model

Robert M., Soga T., Tomita M.

Topics in Current Genetics 18 189 - 234 2007.09

ISSN 16106970

As the workhorse of early studies on metabolism, the metabolic pathways of E. coli are arguably the best characterized. The richness of information available about its pathways is broader than for any other model. However, in spite of decades of descriptive work, only recently can a significant number of E. coli metabolic network constituents be analyzed simultaneously. The advent of metabolomic methods that allow to capture qualitative as well as quantitative information about the intracellular and extracellular metabolite profiles is starting to shed light on the remaining complexity of this simpler model. Here we describe important findings about the physiology of E. coli resulting from emerging metabolomic studies. While a vast number of intracellular metabolites in E. coli still remain to be characterized, the information obtained from those studies can provide an unprecedented amount of information about metabolic pathways including their functional elucidation, enzyme activity, metabolic fluxes, network robustness, or even the discovery of completely novel reactions or pathways. These results are also being used to populate rich databases and to develop computational models of E. coli metabolism that have already proven effective to predict cellular states and will shed light on complex and until now still elusive regulatory principles. © 2007 Springer-Verlag Berlin Heidelberg.

Access to Document (DOI)

Bioinformatic analysis of post-transcriptional regulation by uORF in human and mouse

Matsui M., Yachie N., Okada Y., Saito R., Tomita M.

FEBS Letters 581 ( 22 ) 4184 - 4188 2007.09

ISSN 00145793

RNA decay is thought to exert an important influence on gene expression by maintaining a steady-state level of transcripts and/or by eliminating aberrant transcripts. However, the sequence elements which control such processes have not been determined. Upstream open reading frames (uORFs) in the transcripts of several genes are reported to control translational initiation by stalling ribosomes and thereby promote RNA decay. We therefore performed bioinformatic analysis of the tissue-wide expression profiles and mRNA half-life of transcripts containing uORFs in humans and mice to assess the relationship between RNA decay and the presence of uORFs in transcripts. The expression levels of transcripts containing uORF were markedly lower than those not containing uORF. Moreover, the half-life of the uORF-containing transcripts was also shorter. These results suggest that uORFs are sequence elements that down-regulate RNA transcripts via RNA decay mechanisms. © 2007 Federation of European Biochemical Societies.

Access to Document (DOI)

Sequential logic model deciphers dynamic transciptional control of gene expressions

Yeo Z., Wong S., Vel Arjunan S., Piras V., Tomita M., Selvarajoo K., Giuliani A., Tsuchiya M.

PLoS ONE 2 ( 8 ) 2007.08

Background. Cellular signaling involves a sequence of events from ligand binding to membrane receptors through transcription factors activation and the induction of mRNA expression. The transcriptional-regulatory system plays a pivotal role in the control of gene expression. A novel computational approach to the study of gene regulation circuits is presented, here. Methodology. Based on the concept of finite state machine, which provides a discrete view of gene regulation, a novel sequential logic model (SLM) is developed to decipher control mechanisms of-dynamic transcriptional regulation of gene expressions. The SLM technique is also used to systematically analyze the dynamic function of transcriptional inputs, the dependency and cooperativity, such as synergy effect, among the binding sites with respect to when, how much and how fast the gene of interest is expressed. Principal Findings. SLM is verified by a set of well studied expression data on endo 16 of Strongylocentrotus purpuratus (sea urchin) during the embryonic midgut development. A dynamic regulatory mechanism for endo 16 expression controlled by three binding sites, UI, R and Otx is identified and demonstrated to be consistent with experimental findings. Furthermore, we show that during transition from specification to differentiation in wild type endo16 expression profile, SLM reveals three binary activities are not sufficient to explain the transcriptional regulation of endo16 expression and additional activities of binding sites are required. Further analyses suggest detailed mechanism of R switch activity where indirect dependency occurs in between UI activity and R switch during specification to differentiation stage. Conclusions/Significatwe. The sequential logic formalism allows for a simplification of regulation network dynamics going from a continuous to a discrete representation of gene activation in time. In effect our SLM is non-parametric and model-independent, yet providing rich biological insight. The demonstration of the efficacy of this approach in endo 16 is a promising step for further application of the proposed method. © 2007 Yeo et al.

Access to Document (DOI)

P-BOSS: A new filtering method for treasure hunting in metabolomics

Morohashi M., Shimizu K., Ohashi Y., Abe J., Mori H., Tomita M., Soga T.

Journal of Chromatography A 1159 ( 1-2 ) 142 - 148 2007.08

ISSN 00219673

Metabolomics is expected to boost data driven research. In biomarker discovery, powerful filtering methods to remove noise and outliers are essential for screening significant candidates from the huge volume of omic data. Here we propose a post-measurement peak filtering method (named P-BOSS) for CE electrospray ionization-time-of-flight MS (CE-TOFMS) data. Combining outlier detection method functions in parallel, we applied P-BOSS to the data using Escherichia coli knockout mutants of the tryptophan and purine biosynthesis pathways. As the result, P-BOSS showed remarkably superior performance, reducing 65% of all peaks, while leaving significant peaks. © 2007 Elsevier B.V. All rights reserved.

Access to Document (DOI)

Distinguishing enzymes using metabolome data for the hybrid dynamic/static method

Ishii N., Nakayama Y., Tomita M.

Theoretical Biology and Medical Modelling 4 2007.06

Background. In the process of constructing a dynamic model of a metabolic pathway, a large number of parameters such as kinetic constants and initial metabolite concentrations are required. However, in many cases, experimental determination of these parameters is time-consuming. Therefore, for large-scale modelling, it is essential to develop a method that requires few experimental parameters. The hybrid dynamic/static (HDS) method is a combination of the conventional kinetic representation and metabolic flux analysis (MFA). Since no kinetic information is required in the static module, which consists of MFA, the HDS method may dramatically reduce the number of required parameters. However, no adequate method for developing a hybrid model from experimental data has been proposed. Results. In this study, we develop a method for constructing hybrid models based on metabolome data. The method discriminates enzymes into static modules and dynamic modules using metabolite concentration time series data. Enzyme reaction rate time series were estimated from the metabolite concentration time series data and used to distinguish enzymes optimally for the dynamic and static modules. The method was applied to build hybrid models of two microbial central-carbon metabolism systems using simulation results from their dynamic models. Conclusion. A protocol to build a hybrid model using metabolome data and a minimal number of kinetic parameters has been developed. The proposed method was successfully applied to the strictly regulated central-carbon metabolism system, demonstrating the practical use of the HDS method, which is designed for computer modelling of metabolic systems. © 2007 Ishii et al; licensee BioMed Central Ltd.

Access to Document (DOI)

Gene expression waves: Cell cycle independent collective dynamics in cultured cells

Tsuchyia M., Wong S., Yeo Z., Colosimo A., Palumbo M., Farina L., Crescenzi M., Mazzola A., Negri R., Bianchi M., Selvarajoo K., Tomita M., Giuliani A.

FEBS Journal 274 ( 11 ) 2878 - 2886 2007.06

ISSN 1742464X

The ergodic hypothesis, which assumes the independence of each cell of the ensemble from all the others, is a necessary prerequisite to attach single cell based explanations to the grand averages taken from population data. This was the prevailing view about the interpretation of cellular biology experiments that typically are performed on colonies of billions of cells. By analysing gene expression data of different cells going from yeast to mammalian cell cultures, we demonstrate that cell cultures display a sort of 'ecology-in-a-plate' giving rise to a rich dynamics of gene expression that are independent from reproductive cycles, hence contradicting simple ergodic assumptions The aspecific character of the observed coordinated gene expression activity inhibits any simple mechanistic hypothesis and highlights the need to consider population effects in the interpretation of data coming from cell cultures. © 2007 The Authors.

Access to Document (DOI)

　 Previous page - Next page 　