Functional Genomic Characterisation of the Bacterial Tat Complex as a Nanomachine for Biopharmaceutical Production and a Target for Novel Anti-Infectives (Tat Machine)

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. <P>
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 huge potential for biopharmaceutical production in bacterial species that are already used for this purpose, including Bacillus, Escherichia coli and Stpretomyces. It has furthermore been demonstrated that critical virulence factors are secreted via Tat in important pathogens such as Pseudomonas aeruginosa and E. coli 0157.<P> This proposal aims at the multidisciplinary function genomic characterisation of the Tat nanomachine for both biotechnological and biomedical purposes.<P> We propose to (a) eliminate the current bottlenecks in the Tat nanomachine that limit biopharmaceutical production in Bacillus and Streptomyces; and (b) to use the Tat nanomachine of major Gram-positive and Gram-negative pathogens as a poential target for novel anti-infectives. <P>To reach these goals, the full potential of bioinformatics, comparitive 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