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Towards an understanding of dynamic transcriptional regulation at global scale in bacteria: a systems biology approach

Objective

BaSysBio aims to achieve major breakthroughs in the understanding of the regulation of gene transcription in bacteria at a global scale. The highly dynamic gene regulation is mediated by transcription factors (TF) that trigger or repress the expression of their target genes. Transcription control is embedded into a hierarchical flow of information from genes to phenotype in which many regulatory steps can occur. BaSysBio adopts a systems biology approach in which quantitative experimental data will be generated for each step of the information flow, and will fuel computational modelling. High-throughput technologies (living cell arrays, tiling DNA microarrays, multidimensional liquid chromatography proteomics and quantitative metabolomics) will be developed in conjunction with new computational modelling concepts to facilitate the understanding of biological complexity. Models will simulate the cellular transcriptional responses to environmental changes and their impact on metabolism and proteome dynamics.

The iterative process of simulations and model-driven targeted experiments will generate novel hypotheses about the mechanistic nature of dynamic cellular responses, unravel emerging systems properties, and ultimately provide an efficient roadmap to tackle novel, pathogenic organisms. This system-based strategy will enable BaSysBio i) to understand how transcriptional regulation and metabolism are quantitatively integrated at a global level; ii) to unravel cellular transcriptional responses in conditions mimicking pathogenesis.

Finally, the project will validate the general applicability of the knowledge and integrated modelling-experimental strategy developed in the highly tractable B. subtilis model towards an understanding of regulatory networks controlling pathogenesis in disease-causing bacteria. BaSysBio will make a significant contribution towards overcoming the structural obstacles that hinder the development of systems biology in Europe.

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Coordinator

INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

Address

147, Rue De L'UniversitÉ
Paris

France

Participants (16)

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CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

France

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS

Spain

ERNST-MORITZ-ARNDT-UNIVERSITAT GREIFSWALD

Germany

EIDGENOSSISCHE TECHNISCHE HOCHSCHULE ZÜRICH

Switzerland

GENEDATA AG

Switzerland

INSTITUT PASTEUR

France

INRA TRANSFERT

France

MAX PLANCK SOCIETY REPRESENTED BY MAX PLANCK INSTITUTE FOR MOLECULAR GENETICS

Germany

UNIVERSITY HOSPITAL GRONINGEN

Netherlands

THE PROVOST,FELLOWS AND SCHOLARS OF THE COLLEGE OF THE HOLY AND UNDIVIDED TRINITY OF QUEEN

Ireland

DANMARKS TEKNISKE UNIVERSITET (TECHNICAL UNIVERSITY OF DENMARK)

Denmark

UNIVERSITY OF NEWCASTLE UPON TYNE

United Kingdom

UNIVERSITY OF YORK

United Kingdom

THE UNIVERSITY OF NEWCASTLE AUSTRALIA

Australia

HUMBOLDT-UNIVERSITAET ZU BERLIN

Germany

APPLIED BIOSYSTEMS DEUTSCHLAND GMBH 2906702,00 3230077,00

Germany

Project information

Grant agreement ID: 37469

  • Start date

    1 November 2006

  • End date

    30 April 2011

Funded under:

FP6-LIFESCIHEALTH

  • Overall budget:

    € 16 326 945

  • EU contribution

    € 12 029 619

Coordinated by:

INSTITUT NATIONAL DE LA RECHERCHE AGRONOMIQUE

France