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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 on theme: "Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Towards a “Systems Microbiology” of."— Presentation transcript:

1 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 # 27803 15 May, 2006

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

3 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?

4 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

5 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages 17296 –17301 29 November, 2005

6 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages 17302 –17307 29 November, 2005

7 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group PNAS, vol. 102 no. 48, pages 17302 –17307 29 November, 2005

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

9 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Mol. Genet. Genomics, 267:721-729, (2001).

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

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

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

13 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group http://string.embl.de/

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

15 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

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

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

18 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group 2. Sigma factors -35 -10 TATA

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

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

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

22 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

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

24 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

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

26 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

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

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

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

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

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

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

33 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group J. Mol. Biol., 299:907-930, (2000).

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

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

36 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 -10 -35 mRNA CDS  ’ -10 -35 +1  

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

38 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83:201-212, (2001).

39 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83:201-212, (2001).

40 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83:201-212, (2001).

41 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83:201-212, (2001).

42 Center for Biological Sequence Analysis The Technical University of Denmark DTU Comparative Microbial Genomics group Biochimie, 83:201-212, (2001).

43 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).

44 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, 293:2087-2092 (2001).

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

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