Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Towards a “Systems Microbiology” of.

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Presentation transcript:

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Towards a “Systems Microbiology” of E. coli Dave Ussery Biological Sequence Analysis DTU course # May, 2006

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Part the first: A Brief History of Systems Biology

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group The ability to observe, quantitatively define, quantitatively simulate, and rationally manipulate, the complete gene-expression patterns and molecular-interaction networks of a microbe has created an entirely new scientific discipline: "systems microbiology." What is Systems Microbiology?

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group "Systems Biology" articles in PubMed 157 as of 14 May, 2006

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages – November, 2005

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages – November, 2005

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages – November, 2005

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Part the second: Gene expression in E. coli

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Mol. Genet. Genomics, 267: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Genome Biology, 5:252, (2004).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 1. What is Regulated? 2. How is it Regulated?

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 1. What is Regulated? 2. How is it Regulated?

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Three levels of Regulation ~100,000 proteins/cell ~1,000 proteins/cell 1. Global - chromatin 2. Sigma factors 3. Transcription factors 10 to 100 proteins/cell

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 1. Global - chromatin

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 2. Sigma factors TATA

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 3. Transcription factors

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Comparison of 20 E. coli genomes Interlude:

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Predicted vs. Published Genes a predicted with EasyGene (Larsen and Krogh, 2003)published b GenBank (NCBI) information, genome project databasecontiguous c 16S RNA d TIGR e NARA Institute f U Wisconsin

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Codon usage of selected strains

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 20 “public” genomes at hand a predicted with EasyGene (Larsen and Krogh, 2003)published b GenBank (NCBI) information, genome project databasecontiguous c 16S RNA d TIGR e NARA Institute f U Wisconsin

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group E. coli Core E. coli strain-specific genes Total of 8027 different E. coli gene families

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group DNA curvature Chromatin structure Part the last:

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group J. Mol. Biol., 299: , (2000).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Promoter Structural profile +1 CDS DNA curvature, flexibility important here melts rigid cruciform mRNA CDS  ’  

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83: , (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group plectonemic supercoils Curved DNA RNA polymerase torroidal supercoiling topological boundry Genome Biology, 5:252, (2004).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Ecoli genomic landscape CHRO2003 Data kindly provided by Alain Stintzi protein synthesis electron transport DNA replication, flagella biosynthesis anaerobic growth, alcohol metabolism, acid response stress membrane, secretion aerobic growth, oxidation cell cycle control Genomic landscape of E. coli kindly provided by Josh Stuart, Stanford; Science, 293: (2001).

Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group