Systems Biology in PhotosynthesisINTRODUCTION

Rainer Machné

Institute for Theoretical Chemistry, University of Vienna , AustriaPSI - Photon System Instruments, Czech Republic

Brno, April 3, 2011

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What is Systems Biology?

the simple answer:

mathematical models of biological systems

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What is Systems Biology?

1. What is a System?συστηµα: “a whole compounded of several parts"

2. Systems Theory/Systems Science:the study of interactions of the parts, to understand thebehaviour of the whole, specifically “self-regulatingsystems [...] self-correcting through feedback [...] found innature, including the physiological systems of our body, inlocal and global ecosystems, and in climate” (from wikipedia)

3. Why “Systems Biology”?Mathematical modelling ?

Biology is the science of living ... systemsIs “Systems Biology”, a pleonasm?

3 / 19

What is Systems Biology?

1. What is a System?συστηµα: “a whole compounded of several parts"

2. Systems Theory/Systems Science:the study of interactions of the parts, to understand thebehaviour of the whole, specifically “self-regulatingsystems [...] self-correcting through feedback [...] found innature, including the physiological systems of our body, inlocal and global ecosystems, and in climate” (from wikipedia)

3. Why “Systems Biology”?Mathematical modelling ?

Biology is the science of living ... systemsIs “Systems Biology”, a pleonasm?

4 / 19

What is Systems Biology?

1. What is a System?συστηµα: “a whole compounded of several parts"

2. Systems Theory/Systems Science:the study of interactions of the parts, to understand thebehaviour of the whole, specifically “self-regulatingsystems [...] self-correcting through feedback [...] found innature, including the physiological systems of our body, inlocal and global ecosystems, and in climate” (from wikipedia)

3. Why “Systems Biology”?Mathematical modelling ?

Biology is the science of living ... systemsIs “Systems Biology”, a pleonasm?

5 / 19

Biology vs. Numbers: is biology is a narrative science?1. Statistics:

Mendel, R.A. Fisher (“null hypothesis”), William SealyGosset aka “Student” (“t-test”)

2. Mathematical Models:e. g. oxygen binding to hemoglobin (A.V. Hill), enzymekinetics (Michaelis & Menten, Haldane), cell growth (J.Monod), pattern formation (A. Turing), signal propagationin nerve cells (Hodgkin and Huxley), chemiosmotic theory(P.D. Mitchell)

3. Gene Regulation - Jacob & Monod, Goodwinspecific feedback between metabolism and RNA synthesis

4. Glycolytic Oscillations - B. Chance et al.

5. Metabolic Control Analysis - Kacser

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Biology vs. Numbers: is biology is a narrative science?1. Statistics:

Mendel, R.A. Fisher (“null hypothesis”), William SealyGosset aka “Student” (“t-test”)

2. Mathematical Models:e. g. oxygen binding to hemoglobin (A.V. Hill), enzymekinetics (Michaelis & Menten, Haldane), cell growth (J.Monod), pattern formation (A. Turing), signal propagationin nerve cells (Hodgkin and Huxley), chemiosmotic theory(P.D. Mitchell)

3. Gene Regulation - Jacob & Monod, Goodwinspecific feedback between metabolism and RNA synthesis

4. Glycolytic Oscillations - B. Chance et al.

5. Metabolic Control Analysis - Kacser

Chance B. et al. 1952: The mechanism of catalase action II.Electric analog computer studies. Arch Biochem Biophys 37

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Biology vs. Numbers: is biology is a narrative science?1. Statistics:

Mendel, R.A. Fisher (“null hypothesis”), William SealyGosset aka “Student” (“t-test”)

2. Mathematical Models:e. g. oxygen binding to hemoglobin (A.V. Hill), enzymekinetics (Michaelis & Menten, Haldane), cell growth (J.Monod), pattern formation (A. Turing), signal propagationin nerve cells (Hodgkin and Huxley), chemiosmotic theory(P.D. Mitchell)

3. Gene Regulation - Jacob & Monod, Goodwinspecific feedback between metabolism and RNA synthesis

4. Glycolytic Oscillations - B. Chance et al.

5. Metabolic Control Analysis - Kacser

8 / 19

Biology vs. Numbers: is biology is a narrative science?1. Statistics:

Mendel, R.A. Fisher (“null hypothesis”), William SealyGosset aka “Student” (“t-test”)

2. Mathematical Models:e. g. oxygen binding to hemoglobin (A.V. Hill), enzymekinetics (Michaelis & Menten, Haldane), cell growth (J.Monod), pattern formation (A. Turing), signal propagationin nerve cells (Hodgkin and Huxley), chemiosmotic theory(P.D. Mitchell)

3. Gene Regulation - Jacob & Monod, Goodwinspecific feedback between metabolism and RNA synthesis

4. Glycolytic Oscillations - B. Chance et al.

5. Metabolic Control Analysis - Kacser

9 / 19

Biology vs. Numbers: is biology is a narrative science?1. Statistics:

Mendel, R.A. Fisher (“null hypothesis”), William SealyGosset aka “Student” (“t-test”)

2. Mathematical Models:e. g. oxygen binding to hemoglobin (A.V. Hill), enzymekinetics (Michaelis & Menten, Haldane), cell growth (J.Monod), pattern formation (A. Turing), signal propagationin nerve cells (Hodgkin and Huxley), chemiosmotic theory(P.D. Mitchell)

3. Gene Regulation - Jacob & Monod, Goodwinspecific feedback between metabolism and RNA synthesis

4. Glycolytic Oscillations - B. Chance et al.

5. Metabolic Control Analysis - Kacser

Mathematical models were always part of Biology and quite nor-mal until 1960ies/1970ies - What happened?

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Gene-regulatory Feedback Cycles:

d Xi

d t=

ai

Ai + kiYi− bi

d Yi

d t= αiXi − βi

Xi Yi

negative feedback

Xi ... concentration of mRNA iYi ... concentration of protein i

Goodwin B. 1965: Oscillatory behavior in enzymatic control processes.Advances in Enzyme Regulation 3:425-428

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What happened tomathematics in biology?

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genes>Cyanothece ATCC51142 D1 (psbA) gene, complete cdsAAACATTTGATTAATCTTCTTTACAAAACTTGACGAATTGTTTAAGATAAAAATGTCAATACAAAACGTACCTTGACAAATAAATAAAGGAATCATAACCATGACTACTACCTTACAACAACGCGAGAGCGTTTCCTTGTGGGAACAGTTTTGTCAGTGGGTGACCAGCACCAACAACCGCATCTATGTCGGTTGGTTCGGTACCTTAATGATCCCCACCCTCTTAACTGCTACCACCTGTTTCATCATTGCTTTCATCGCTGCTCCTCCTGTGGACATCGATGGTATCCGTGAGCCTGTAGCTGGTTCTTTACTCTACGGAAACAACATCGTTTCCGGTGCAGTCGTACCTTCTTCTAATGCTATCGGTCTACACTTCTATCCCATCTGGGAAGCTGCTTCACTTGATGAGTGGCTTTACAATGGCGGTCCTTACCAGTTAGTAATTTTCCACTTCTTAATCGGAATCTTTTGCTACATGGGTCGTCAGTGGGAACTTTCCTACCGTTTAGGAATGCGTCCTTGGATCTGTGTTGCCTACTCTGCACCTGTATCCGCACGGACCGCAGTATTCTTAATCTACCCCATCGGACAAGGTTCTTTCTCTGATGGTATGCCTTTAGGAATCTCCGGAACCTTCAACTTCATGTTCGTGTTCCAAGCTGAACACAACATCTTGATGCACCCCTTCCATATGTTGGGTGTTGCTGGTGTATTCGGTGGATCTTTATTCTCCGCTATGCACGGTTCCTTAGTAACCTCTTCTTTAGTTCGTGAAACCACTGAAATCGAGTCTCAAAACTACGGTTACAAGTTCGGACAAGAAGAAGAAACCTACAACATCGTAGCTGCTCACGGTTACTTTGGTCGTTTAATCTTCCAATACGCATCCTTCAACAACAGCCGTGCTTTACACTTCTTCTTAGGTGCATGGCCTGTAATCGGTATCTGGTTCACCGCAATGGGTGTATCCACCATGGCTTTCAACTTAAACGGATTTAACTTCAACCAGTCTATCCTTGATTCTCAAGGCCGTGTAATCGGAACCTGGGCTGATGTATTAAACCGTGCAGGAATCGGAATGGAAGTAATGCACGAGCGTAACGCTCACAACTTCCCCTTAGACTTAGCTTCTGCTGAGCCTGTATCTGCTCCTGTTATCAATGGTTAATTCCTTTGATAATAACTGAATAATACACTAAGCACTCCCAAGTTTGGGGGTGCTTTTTTTTTCTGTAACTAATACTCTTTTAATTATTAATCAAAA

Welsh et al. 2008: The genome of Cyanothece 51142, a unicellular diazotrophiccyanobacterium important in the marine nitrogen cycle. PNAS 105(39):15094-9

Prohaska SJ, Stadler PF 2008: “Genes”. Theory Biosci. 127(3):215-21.13 / 19

genes

◮ Advent of recombinant technology let to quickincrease in knowledge , however stillincomplete

◮ Data (knock-outs) was only boolean, qualitativeat best (gels & blots)

◮ Batch cultivation:unstable conditions , unspecific effects, weakreproducability

◮ Ill-posed inverse problems: too many (known andunknown) unknowns, too many parameters

◮ Models can not be verifiedEnrico Fermi: “my friend Johnny von Neumann used to say,with four parameters I can fit an elephant, and with five Ican make him wiggle his trunk.”

Incomplete and Qualitative DataNot Compatible with ModellingBiology became descriptive again!

Dyson F. 2008: A meeting with Enrico Fermi. Nature 427:297

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What is Systems Biology?

data acquisition

1980−90 genome analysisbioinformatics

1990−2000

in silico simulation

sequencingHT nucleotide HT genome−scale

1957lac operon (1961)

analog simulation simulation ofmetabolic networks

in silico modelsfor viruses andred blood cells

1980−90

molecular biologyprogress

1960−70

1960−65

1970−80

1995−2000

1990−1998

genome−scale models

SYSTEMS BIOLOGYmetabilism regulation

c©David Šafranek

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What is Systems Biology?

d Xi

d t=

ai

Ai + kiYi− bi

d Yi

d t= αiXi − βi

+

Cyanothece sp. ATCC 51142circadian transcriptome

c©Jason McDermott 2009 ISCB/ECCB

Systems Biology:Mathematical modelling + omics data

Quantitative Biology:Exact and quantitative measurements+ controlled and stable conditions

Stöckel J et al. 2008: Global transcriptomic analysis of Cyanothece 51142 revealsrobust diurnal oscillation of central metabolic processes. PNAS 105(16):6156-6161

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What is Systems Biology?

d Xi

d t=

ai

Ai + kiYi− bi

d Yi

d t= αiXi − βi

+

Cyanothece sp. ATCC 51142circadian transcriptome

c©Jason McDermott 2009 ISCB/ECCB

Systems Biology:Mathematical modelling + omics data

Quantitative Biology:Exact and quantitative measurements+ controlled and stable conditions

Stöckel J et al. 2008: Global transcriptomic analysis of Cyanothece 51142 revealsrobust diurnal oscillation of central metabolic processes. PNAS 105(16):6156-6161

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Quantitative Biology

Exact and quantitative measurements+ controlled and stable conditions

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Got headaches?

normal people good in math mathematician

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