how is life (and its origin) organized? · e. coli model (ii) – regulated network •...
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How is life (and its origin) organized?
Pietro Speroni di Fenizio, Naoki Matsumaru,Florian Centler, Christoph Kaleta and Peter Dittrich
Bio Systems Analysis GroupFSU Jena
Friedrich-Schiller-Universität Jena Jena Centre for BioinformaticsBMBF (Federal Ministry of Education and Research, Germany) 0312704A, DFG (German Research Foundation) Grant Di 852/41
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Bio Systems Analysis Group
Use computational approaches to explain complex dynamical phenomena found in living systems
ESIGNET – Evolving Cell Signalling
Networks in silico(T. Hinze, T. Lenser, EU)
Chemical Network Theory and Simulation
(P. Speroni d.F., F. Cenler, BMBF)
Semantics of Biological Models
(Ch. Knüpfer, RLS)
Systems Analysis of the Cell Cycle(B. Ibrahim, DAAD)
Organic Computing: Chemical Prgramming
(N. Matsumaru, DFG)
Autonomous Experimentation(N. Matsumaru, BMBF)
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How is life (and its origin) organized?
2. What is the biochemical organization of an organism?
4. How did the biochemical organization of the preprebiotic soup evolved?
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Q1
lattice of organizations = organizational structure
How does the lattice of organizations of an organism looks like?
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What is an answer ?
[Source: Puchalka/Kierzek (2004)Biophys. J. 86, 1357]
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„ Chemical Organization“
Organization := a set of molecules that is(algebraically) closed andselfmaintaining
There is no reaction producingany other molecules
than the member of the set.
Within the set, all moleculesconsumed by a reaction
can be reproduced by a reaction.
[Speroni di Fenizio/Dittrich (2005/7) inspired by Fontana, Buss, Kauffman, Maturana, Varela, Uribe]
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Fixed Point and Organization
TheoremGiven a fixed point of the ODE describing the dynamics
of a reaction system, then the set of molecules represented by that fixed point is an organization.
[Dittrich/Speroni di Fenizio, (2005,2007)]
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Practical View
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Chemical Organization
Theory
Reaction network
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Organization
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All Organizations
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Chemical Organization
Theory
OrganizationsReaction network
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Organization
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Lattice of Organizations
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{1}
{2, 3}
{1,2,3,4}
{ }
Hasse diagram of the organizations
OrganizationsReaction network
Chemical Organization
Theory
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Generate Organization
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{1}
{2, 3}
{1,2,3,4}
{ }
Hasse diagram of the organizations
OrganizationsReaction network
Chemical Organization
Theory
GO({3, 4}) = ?
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Generate Organization
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{1}
{2, 3}
{1,2,3,4}
{ }
Hasse diagram of the organizations
OrganizationsReaction network
Chemical Organization
Theory
GOrg({3, 4}) = {1}
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Union of Organizations
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{1}
{2, 3}
{1,2,3,4}
{ }
Hasse diagram of the organizations
OrganizationsReaction network
Chemical Organization
Theory
GOrg({3, 4}) = {1}
{1} UO {2, 3} := GOrg({1} U {2,3})
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Q1
organizational structure = lattice of organizations
How does the lattice of organizations of an organism looks like?
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Trivially, all organisms have at least one organization
S
O
W2
S + O 2O + WSO
W
{S, O, W}
{S}
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Is there more?
S + O1 2O1 + WS + O2 2O2 + W
SO
W
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Is there more?
S + O1 2O1 + WS + O1 + O2 2O2 + W
SO
W
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How does the lattice organizations in an organism looks like?
• number?• hight?• size distribution?
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We looked at a couple of network models of “ real” systems
• photochemistries (dead, closed but not isolated systems)
• metabolism• regulated metabolism• lambdaphage• HIV immunesystem
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Photochemistry
Y. L. Yung and W. B. DeMore (1999)Photochemistry of Planetary Atmospheres,Oxford University Press
http://www.fpsoftlab.com/images/screenshots/mars640x4801.jpg
31 molecular species,103 reactions
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76 Species, incl.28 Input
Glucose
76 + 2 = 78 SpeciesGlucose
78 + 6 = 84 SpeciesGlucose + Lactose
All 92 SpeciesGlucose + Glycerol + Lactose
78 + 8 = 86 SpeciesGlucose + Glycerol
E. coli Model (I)
• F. Centler, P. Speroni di Fenizio, N. Matsumaru, P. Dittrich (2007); in: Modeling and Simulation in Science Engineering and Technology, Postproceedings of ECMTB 2005, Dresden (in print)
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E. coli Model (I)
• F. Centler, P. Speroni di Fenizio, N. Matsumaru, P. Dittrich (2007); in: Modeling and Simulation in Science Engineering and Technology, Postproceedings of ECMTB 2005, Dresden (in print)
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E. coli Model (II) – Regulated Network
• Palsson/Covert• Organization theory is able to predict
growth phenotypes of various mutants quite nicely
• But the organizational structure is simple
• C. Kaleta, F. Centler, P. Speroni di Fenizio, P. Dittrich (2007), submitted
{S, O, W}
{S}
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E. coli Model (III)
• network from Palsson et al (?)
• analysis by C. Kaleta 2006
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E. coli Model (III)
central metabolism+
lipid synthesisACP or hmrsACP
pyrimidine nucleotide synthesisq8 (quinone)
synthesis of some dNTPs
Minimal growth scenario:DGlucose, O2, Fe2, NH4, H+, Pi, SO4
• analysis by C. Kaleta, F. Centler, 2006
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HIV Models
• N. Matsumaru, F. Centler, P. Speroni di Fenizio, P. Dittrich (2006); it Information Technology, 48(3):19,
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HIV Models
• N. Matsumaru, F. Centler, P. Speroni di Fenizio, P. Dittrich (2006); it Information Technology, 48(3):19
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How does the lattice of organizations of an organism looks like?
?
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Q2
What is the characteristics of the organizational evolution? upward? downward? ...
How did the biochemical organization of the preprebiotic soup evolved?
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A View of Chemical Evolution
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Actual Evolution
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Actual Evolution
Actual Evolution vs.
Organizational Evolution
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Organizational Evolution
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Organizational Evolution
1. Upwards [t1—t2]21 tt OO ⊂
{1}
{2, 3}
{1,2,3,4}
{ }
Dynamics
[2][3]
[4][1]
Hasse diagram of organizations
Organizations
t1 t2
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Organizational Evolution
1. Upwards [t1—t2]
3. Downwards [t2—t3]
21 tt OO ⊂
{1}
{2, 3}
{1,2,3,4}
{ }
Dynamics
[2][3]
[4][1]
Hasse diagram of organizations
Organizations
t1 t2 t3
32 tt OO ⊃
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Organizational Evolution
1. Upwards [t1—t2]
3. Downwards [t2—t3]
5. Sidewards [t1—t3]
21 tt OO ⊂
{1}
{2, 3}
{1,2,3,4}
{ }
Dynamics
[2][3]
[4][1]
Hasse diagram of organizations
Organizations
t1 t2 t3
32 tt OO ⊃
otherwise
A set of existing species and an organization are not equivalent.e.g., {2,3,4}
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Theoretical vs. Practical
• Theoretically:– Every possible species is known.– Entire reaction network is given.→Every possible organization can be calculated.→It is possible to define the dynamics on the ODE
• Practically:– NOT every possible species is known.– the entire network is NOT given.→NOT evey possible organization can be
calculated.
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Perspective Change
{1}
{2, 3}
{1,2,3,4}
{ }
Dynamics
[2][3]
[4][1]
Hasse diagram of the organizations
Organizations
t1 t2 t3
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Perspective Change
Dynamics
[2][3]
[4][1]
t1 t2 t3
{1}
{2, 3}
{1,2,3,4}
{ }
{1}
{ }
{1}
{2, 3}
{1,2,3,4}
{ }
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Downward movement
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Upward Movements(adding mutations)
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Q2
What is the characteristics of the organizational evolution? upward? downward? ...
How did the biochemical organization of the preprebiotic soup evolved?
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Q2 - Notes
• There are two levels of chemical evolution.– Actual evolution
(the actual vessel)
– Organizational evolution(upward, downward, sideward movements)
• These levels are different.• If the organizations are complex, a
downward movement (organizational level) can lead to a state with a higher diversity (actual evolution).
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Http://www.mbl.edu/Astrobiology/Riley/image/E.coli.gif
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vs.
beauty of mathematics
unaccesibilty of the real worldvs.
crule abstraction of mathematics
beauty of the real world
vs.
Acknowledgements
Pietro Speroni di Fenizio, Naoki Matsumaru,Florian Centler, Christoph Kaleta
Friedrich-Schiller-Universität Jena Jena Centre for BioinformaticsBMBF (Federal Ministry of Education and Research, Germany) 0312704A, DFG (German Research Foundation) Grant Di 852/41