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Tat machine


Functional genomic characterisation of the bacterial Tat complex
EC contribution
: € 2.000.000
Duration
: 48 months
Starting date
: 01/11/2004
Funding scheme
: Specific Targeted Research Project
Keywords
: anti-infectives, biopharmaceuticals, nanomachines, twin-arginine translocation, Bacillus, E. coli, Staphylococcus, Streptomyces
Contract/Grant agreement number
: LSHG-CT-2004-005257
Project web-site
: -

Background:

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, yetbut 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.
The Tat machine project sought to eliminate existing bottlenecks in the Tat nanomachine that limit biopharmaceutical production in Bacillus, E. coli and Streptomyces, as well as to 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.

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