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Introduction to systems

biology

Victor Sourjik, ZMBH, Heidelberg

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Where is the place of systems biology?

Organisms

Cells

Networks

Proteins/Genes

Organismic biology

Cell biology

Systems biology

Molecular biology / Biochemistry

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What are the ingredients of systemsbiology?

Cell

mRNA profile

Protein profile

Protein-DNA

(Transcriptionalnetwork)

Protein-Protein

(Signalling networks;multimeric complexes)

Protein localisation

Intracellular dynamics

Metabolic

networks

Genom

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Methods of systems biologyGenomics/Transcriptomics- Genom sequencing

- High-throughput mRNA expression analysis- Genetic interactions

Proteomics-Protein chips-Two-hybrid assays

-Mass-spektrometry / 2D gels-High-throughput protein localisation

Chemical libraries

Metabolomics

Data analysis- Bioinformatics / microarray analysis

- Netzwork analysis and mathematical modellingGavin et al.,, Nature 415, 141 (2002)

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mRNA profiling (microarrays)

Schulze & Downward, Nat. Cell Biol. 3, E160 (2001)

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Transcriptional networks

Lee et al., Science 298, 799 (2002)

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Transcriptional networks

Lee et al., Science 298, 799 (2002)

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Transcriptional networks

Lee, 2002

Babu et al., Curr. Opin. Struct. Biol. 14, 283 (2004)

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Transcriptional networksMotifs

Lee et al., Science 298, 799 (2002)

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Genetic interactions

Tong et al., Science 294, 2364 (2001)

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2D gels

2DGE of S. cerevisiae

Fey & Larsen, Cerr. Opin. Chem. Biol. 5, 26 (2001)

2D DIGE

Dye1 Dye2 Dye3

Marouga et al.,Anal. Bioanal. Chem. 382, 669(2005)

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Protein chips

Analytical Functional

Phizicky et al., Nature 422, 210 (2003)

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Two-hybrid assays

Fields, FEBS Journal 272, 5391 (2005)

Phizicky et al., Nature 422, 210 (2003)

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Two-hybrid assays

Giot et al.,Science 302, 1727 (2003)

TH network in Drosophila

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Localization

S. cerevisiae

Huh et al., Nature, 425, 686 (2003)

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Metabolic networks

KEGG

Weckwerth, Annu. Rev. Plant Biol. 54, 669 (2003)

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Computer modelling and simulations

Network structure

Eungdamrong & Iyengar, Trends Cell Biol. 14, 661 (2004)

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Computer modelling and simulationsAnalysis

Motifs: feed-forward relay

Eungdamrong & Iyengar, Trends Cell Biol. 14, 661 (2004)

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Computer modelling and simulationsSimulation (deterministic / stochastic)

Papin et al., Nat. Rev. Mol. Cell Biol. 6, 99 (2005)

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Computer modelling and simulationsSimulation (deterministic / stochastic)

Web-Tools

Eungdamrong & Iyengar, Trends Cell Biol. 14, 661 (2004)

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Data integration

Papin et al., Nat. Rev. Mol. Cell Biol. 6, 99 (2005)

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Systems biology flow chart

Function and structure

of components

Connections

Live cell dynamics

and regulation

Computer modelling

H

ow?

?

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Synthetic biology

Elowitz & Leibler, Nature 403, 335 (2000)

Spinzak & Elowitz, Nature 438, 443 (2005)

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Synthetic biology

Spinzak & Elowitz, Nature 438, 443 (2005)

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Synthetic biology

Problems:

Non-optimality

Lack of robustness to perturbations

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Synthetic biology

Min system

(natural)

Repressilator

(synthetic)

Elowitz & Leibler, Nature 403, 335 (2000)Lutkenhaus, Ann. Rev. Biochem. 76, 14 (2007)