Systems Biology in Photosynthesis INTRODUCTION
Transcript of Systems Biology in Photosynthesis INTRODUCTION
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?
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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?
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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?
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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
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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
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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
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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
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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