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Complex systems and biology
Biological systems
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are composed of large numbers of functionally diverse elements,
these elements interact selectively and nonlinearly,
they have a function that they need to perform.
The interactions between elements form a network.
Understanding the dynamical behavior of these systems necessitates the
understanding of their interconnections.
An abstract representation of interaction networks and theoretical modeling
can give general insights into system-level behavior.
Gene expression is controlled by gene
regulatory networks
Network of the Drosophila segment polarity genes
mRNA
PROTEIN
PROT
COMPL
repression
translation,
activation,
modification
cell
neighbor cell
R. Albert, H. G. Othmer, Journ. Theor. Biol. 223, 1 (2003)
Cells respond to their environment by using
signal transduction networks
E. coli
attractor
receptor
motor
flagella
tumbles
swims
Abstract representation of the bacterial
chemotaxis signal transduction network
R. Albert, Y-W Chiu, H. G. Othmer, submitted
Signal transduction in plant guard cells
CO2
Stomatal closure
Light
Light
+ ABA
– ABA
H2O
Thanks to Sally Assmann, PSU
Thanks to Song Li, PSU
Modeling and experiments
It is extremely important that models of biological networks are based on
a synthesis of experimental knowledge about the system.
Input: components; states of components, interactions
Hypotheses: kinetics.
Validation: capture known behavior.
Explore: study cases that are not accessible experimentally
change parameters, change assumptions
Give predictions, gain insights
Overall goal: identify common properties of biological networks
dynamical: high amplification, robustness, adaptability,
topological: redundancy, modularity, conserved regulatory
motifs
Topology of the yeast protein interaction
network
The heterogeneous organization is a
common feature of numerous
biological and non-biological networks.
This implies robustness to random
mutations, but vulnerability to
mutations in highly-connected
proteins.
R. Albert, H. Jeong, A.-L. Barabási, Nature 406, 378 (2000)
H. Jeong, S.P. Mason, A.-L. Barabasi, Z.N. Oltvai, Nature 411, 41-42 (2001)
Identifying general themes in biological
networks
Can we identify subsets of the network that have well defined roles?
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Two antagonistic activating clusters…
that enforce each other in neighboring cells
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A regulatory source that maintains asymmetry.
Regulatory motifs
Flip-flop
Negative feedback loop