Functional analysis of conserved hypothetical proteins in prokaryotes

• Applicant: Dr. Peter Uetz
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 12775233

Currently more than 100 bacterial genomes have been completely sequenced but about one third of their genes have no known function. I suggest to address this problem by identifying all physical interactions among the -1,000 proteins of Treponema pattidum by systematic two-hybrid screens. Interactions of uncharacterized proteins will suggest possible functions for these proteins. Although T, pallidum encodes about 750 proteins which are conserved in other bacteria, I suggest to concentrate on -180 conserved hypothetical proteins. Our screen will not only provide first functional insights into these proteins but this functional information can be confidently transferred to homologous proteins in more tractable model species such as E.. coli, in which our predictions can be experimentally verified, e.g. by generating mutations. The genome of T. pallidum is four times smaller, than the genome of E.. coli.. Thus our project will be more than one order of magnitude smaller than a comparable project in E. coli because the number of experiments grows exponentially with the number of genes. Pilot screens in our. laboratory using several flagellar proteins have shown that the proposed strategy is (1) highly efficient and informative, (2) provides novel information on both characterized and uncharacterized proteins, (3) makes correct functional (experimentally verifiable) predictions, and (4) will devise technologies that can be applied to other genomes as well, including eukaryotic ones.

• DFG Programme: Research Grants
• International Connection: USA