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Comparative genomics of bacteria: functional annotation, metabolic reconstruction, evolution of metabolic pathways and regulatory systems

Objective

Sequencing of bacterial genomes has created both a challenge and an opportunity for bioinformatics. It is a challenge because the genome sequencing rate exceeds the capacity of manual annotation, and it is an opportunity because it allows one to use comparative techniques for genome annotation, and to study function and evolution of metabolic pathways and regulatory systems and, eventually, complete genomes. The main technical objectives of this project are development and integration of methods for functional annotation of genomes, including gene recognition, functional annotation of genes, identification of regulatory signals; comparative approaches to metabolic reconstruction; tools for genome alignment and synteny analysis, and application of the developed software for analysis of concrete genomes. The fundamental research will be directed towards evolution of genomes, metabolic pathways and regulatory systems, with particular attention on: metabolic systems subject to complex regulation by multiple interacting systems; taxon-specific regulation and microevolution of regulons and regulatory sites; and structural properties and evolution of regulatory protein-DNA interactions. We will also continue manual analysis of selected metabolic pathways and regulatory systems, leading to annotation of new protein functions and identification of regulatory signals, with special attention towards prediction of transporter specificity. We will attempt to formulate models of evolution of regulatory sites, regulons (sets of co-regulated genes) and regulatory systems. The proposed research combines main aspects of contemporary bioinformatics, from application of probability theory to algorithm development, software implementation, and analysis of real data, and from genome sequence analysis to structural studies. All teams have strong background in bioinformatics and, in particular, in comparative genomics. The consortium members collaborate since 1999. In 2000-2002 several teams collaborated in the INTAS project 99-1476, and the developed methods and algorithms will be used as research tools in the present project. The research program requires tight integration between the participating teams. The created software will be immediately used for genome analysis, and the provided users' feedback will be taken into account in subsequent releases. Analysis of metabolic and regulatory systems will create data for large-scale functional, structural, and evolutionary studies. Conversely, understanding of general principles of metabolic and regulatory evolution will lead to creation of better tools for functional annotation. Thus the proposed project will result both in development of tools for genome analysis and, specifically, prediction of bacterial phenotype (metabolic capabilities, regulation, response to stress and external stimuli) from genomic data, and deeper understanding of all aspects of genome structure, function and evolution.

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Coordinator

TECHNISCHE UNIVERSITÄT MÜNCHEN

Address

Am Forum, 1
Freising

Germany

Administrative Contact

Dmitrij FRISHMAN

Participants (7)

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CONSIGLIO NAZIONALE DELLE RICERCHE (CNR)

Italy

INSTITUT NATIONAL DE RECHERCHE EN INFORMATIQUE ET AUTOMATIQUE (INRIA)

France

INSTITUTE OF GENETICS AND SELECTION OF INDUSTRIAL MICROORGANISMS (GOSNIIGENETIKA)

Russia

INSTITUTE OF INFORMATION TRANSMISSION PROBLEMS

Russia

INSTITUTE OF THEORETICAL AND EXPERIMENTAL BIOPHYSICS

Russia

MOSCOW STATE UNIVERSITY (MGU)

Russia

MOSCOW STATE UNIVERSITY (MGU)

Russia

Project information

Grant agreement ID: INTAS 2005-1000008-8028

  • Start date

    1 September 2006

  • End date

    28 February 2009

Funded under:

IC-INTAS

  • Overall budget:

    € 144 250

  • EU contribution

    € 140 000

Coordinated by:

TECHNISCHE UNIVERSITÄT MÜNCHEN

Germany