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Functional genomic characterization of the bacterial Tat complex as a nanomachine for biopharmaceutical production and a target for novel anti-infectives

Objective

Bacterial protein secretion is a fundamental biological process of the utmost relevance to human health. On one hand, this process can be exploited successfully to the benefit of human health through the biotechnological production of biopharmaceuticals. On the other hand, secreted bacterial toxins and virulence factors represent a major threat to human health. The Twin-arginine translocation (Tat) machinery represents a recently discovered, but widely conserved system for bacterial protein secretion. This multi-subunit nanomachine can transport fully folded proteins and thus has a huge potential for biopharmaceutical production in bacterial species that are already used for this purpose, including Bacillus, Escherichia coli and Streptomyces. It has furthermore been demonstrated that critical virulence factors are secreted via Tat in important pathogens, such as Pseudomonas aeruginosa and E. coli O157.
The Tat machine programme aims at the multidisciplinary functional genomic characterisation of the Tat nanomachine for both biotechnological and biomedical purposes. We will: (A) eliminate the current bottlenecks in the Tat nanomachine that limit biopharmaceutical production in Bacillus, E. coli and Streptomyces; and (B) characterise the structure and function of Tat nanomachines from a few selected Gram-positive and Gram-negative bacteria, including major pathogens. To reach these goals, the full potential of bioinformatics, comparative and structural genomics, and proteomics will be exploited. The Tat machine partnership has a proven track record in the application of these cutting-edge technologies and includes Europe's leading groups in the field of Tat machinery analysis.

Field of science

  • /natural sciences/biological sciences/microbiology/bacteriology
  • /natural sciences/biological sciences/biochemistry/biomolecules/proteins

Call for proposal

FP6-2003-LIFESCIHEALTH-I
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Funding Scheme

STREP - Specific Targeted Research Project

Coordinator

UNIVERSITY OF GRONINGEN
Address
Broerstraat 5
Groningen
Netherlands

Participants (10)

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE
France
Address
Rue Michel-ange 3
Paris
ERNST-MORITZ-ARNDT-UNIVERSITÄT GREIFSWALD
Germany
Address
Domstrasze 14
Greifswald
FORSCHUNGZENTRUM JÜLICH GMBH
Germany
Address
Leo-brandt-strasse
Jülich
GENENCOR INTERNATIONAL B.V.
Netherlands
Address
Archimedesweg 30
Leiden
IMPERIAL COLLEGE OF SCIENCE, TECHNOLOGY AND MEDICINE
United Kingdom
Address
Exhibition Road
London
MAX-PLANCK SOCIETY FOR ADVANCEMENT OF SCIENCE
Germany
Address
Hofgartenstr. 8
München
UNIVERSITY OF DUNDEE
United Kingdom
Address
Nethergate
Dundee
UNIVERSITY OF EAST ANGLIA
United Kingdom
Address
University Plain 1
Norwich
UNIVERSITY OF WARWICK
United Kingdom
Address
Gibbet Hill Road
Coventry
UNIVERSITÄTSKLINIKUM FREIBURG
Germany
Address
Hugstetterstrasse 49
Freiburg