Introduction to systems

biology
Victor Sourjik, ZMBH, Heidelberg
 Why do we need systems biology?
KEGG
Where is the place of systems biology?

Organisms Organismic biology

Cells Cell biology

Networks Systems biology

Proteins/Genes Molecular biology / Biochemistry

Why do we understand under systems
biology?
Alternative definitions of
systems biology

- qualitative analysis of large

protein / gene networks („omics“)

-detailed quantitative analysis of

small systems / functional modules
(„bottom-up approach“)

- low-precision modelling of entire

cells / organisms
(„top-down“ approach)
 What are the ingredients of systems
biology?

Cell

Genom

mRNA profile Protein-DNA Protein-Protein Protein localisation Metabolic

Protein profile (Transcriptional (Signalling networks; Intracellular dynamics networks
network) multimeric complexes)
 Methods of systems biology
Genomics/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
Gavin et al.,, Nature 415, 141 (2002)
- Netzwork analysis and mathematical modelling
mRNA profiling (microarrays)

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

Transcriptional networks

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

Transcriptional networks

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

Transcriptional networks

Lee, 2002

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

Transcriptional networks
„Motifs“

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

Genetic interactions

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

 2D gels
2DGE of S. cerevisiae 2D DIGE
Dye1 Dye2 Dye3

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

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

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

Analytical Functional
 Two-hybrid assays
Phizicky et al., Nature 422, 210 (2003)

Fields, FEBS Journal 272, 5391 (2005)

 Two-hybrid assays
Phizicky et al., Nature 422, 210 (2003)

Ito et al., Trends Biotechnol. 19, S23 (2001)

Two-hybrid assays
TH network in Drosophila

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

 Mass spectrometry
MS network in S. cerevisiae

Gavin et al.,, Nature 415, 141 (2002)

Kumar & Snyder, Nature 415, 123 (2002)

Localization
S. cerevisiae

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

 Metabolic networks
KEGG

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

Computer modelling and simulations

Network structure

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

Computer modelling and simulations
Analysis
Motifs: feed-forward relay

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

Computer modelling and simulations
System of ODEs

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

Computer modelling and simulations
Spatial modelling

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

Computer modelling and simulations
Simulation (deterministic / stochastic)

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

Computer modelling and simulations
Simulation (deterministic / stochastic)

Web-Tools

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

Data integration

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

 Systems biology “flow chart”

Function and structure

of components

Connections
How?

Live cell dynamics

and regulation

Computer modelling

?
 Synthetic biology

Elowitz & Leibler, Nature 403, 335 (2000)

Spinzak & Elowitz, Nature 438, 443 (2005)
 Synthetic biology

Spinzak & Elowitz, Nature 438, 443 (2005)

Synthetic biology

Problems:

Non-optimality

Lack of robustness to perturbations

 Synthetic biology
Min system Repressilator
(natural) (synthetic)

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