A Systems Model of Signaling Identifies a Molecular Basis Set for CytokineInduced Apoptosis

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A Systems Model of Signaling Identifies a
Molecular Basis Set for Cytokine-Induced Apoptosis

• Kevin A. Janes, John G. Albeck, Suzanne Gaudet,
  Peter K. Sorger, Douglas A. aiffemburger,
  Michael B. Yaffe

Science 310, 1646 (2005)
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What is systems model?

• A mathematical formalism that predicts cellular
  responses
• A method derived from Systems Biology

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Systems Biology

• Not focus on individual genes and proteins
• Focus on the behavior and relationships of all
  components in a particular biological system
• Functional perspective study

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A system-level understanding of a biological
system

• System structures
• A network of gene interactions and biochemical
  pathways
• System dynamics
• How a system behaves over time under various
  conditions
• The control methods
• Mechanisms that control the system
• The design methods
• Modify and construct biological systems that can
  have a desired properties

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Grouch about systems biology

• The fundamental misconception of systems biology
  advocates is that one could create a virtual
  cell and use big computers to model life and
  make discoveries. One makes discoveries by
  watching, working, checking. They want to be
  Darwin, but do not want to waste years on the
  Beagle.They want to sex but no love, icing but no
  cake. Scientific pornography.
• Dutchman Ronald Plasterk. Current Biology Nov.
  8, 2005

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A systems Models of signaling Identifies a
Molecular Basis set for cytokine-Induced apoptosis
Measurement of single molecular signal can not
predict the apoptosis correctly
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A systems Models of signaling Identifies a
Molecular Basis set for cytokine-Induced apoptosis
Extracellular inputs (Cytokines)
Cell responses
Apoptosis
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A systems Models of signaling Identifies a
Molecular Basis set for cytokine-Induced
apoptosis

• Experimentally measured 7980 molecular signals
  and 1440 response output for cytokine induced
  apoptosis
• Made the mathematic model to predicts the 12
  cytokine-induced apoptotic out-puts
• Predicted apoptosis regulation by means of
  autocrine circuits
• The model identifies stress-apoptosis and
  survival signaling axes

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1. Experimentally measured 7980 molecular
signals and 1440 response out put for cytokine
induced apoptosis
Using the established signaling pathway to build
a model
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1. Experimentally measured 7980 molecular signals
and 1440 response out put for cytokine induced
apoptosis
Experiment design and results
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2. The mathematic model to predicts the 12
cytokine-induced apoptotic out-putsfrom 660
element signaling vector
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3. Predicted apoptosis regulation by means of
autocrine circuits
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3. Predicted apoptosis regulation by means of
autocrine circuits
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4. The model identifies stress-apoptosis and
survival signaling axes
Simplify the model with biological knowledge
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4. The model identifies stress-apoptosis and
survival signaling axes
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4. The model identifies stress-apoptosis and
survival signaling axes
The same molecular, such as IKK, can convey
either pro- or antiapototic messages, depending
on the timing and mechanism of activation.
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4. The model identifies stress-apoptosis and
survival signaling axes
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Conclusion
Our work illustrates how a complex signaling
network can be reduced empirically to a much
simple computational model that is directly tired
to biological mechanism
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My point of view about this paper

• Why didnt they use the other type of cell line
  to verify this model?
• colon cell line to study the effect of insulin on
  apoptosis?

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My points of view on systems biology

• Systems biology is not a new concept, but a new
  name
• Innovative aspects to attract new funding?
• Systems biology use new tools
• High-throughput experimental methods
• Super computer
• Systems biology changes the way of our research
• Hypothesis driven vs. ignorance driven

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My points of view on systems biology

• The contribution of Systems biology
• Mature science Physics
• The equations were formulated more than a
  hundred years ago
• The theory is established and used to guide the
  design of new experiments.
• Immature science Molecular biology
• major breakthroughs are achieved only
  experimentally by trial-and error.

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Biology is becoming a mature science prescriptiv
e vs. predictive
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Systems biology in neuroscience
Grant SG. Curr Opin Neurobiol 2003 Oct 13(5)
577-82
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Examples of systems neuroscience

• Brain Work and Brain Imaging
• Raichle. ME. et al. Annual Review of
  Neuroscience 2006 Apr. 20

• Single neurons as experimental systems in
  molecular biology
• Hinkle D. et al. Progress in Neurobiology
  2004. Feb 72 (2) 129-42

• Systems neurobiology without backbones
• Greenspan RJ. Current Biology, Vol 14,
  R177-R179, 9 March 2004

• Complete functional characterization of
  sensory neurons by system identification
• Wu MC. et al. Annual Review of Neuroscience
  2006 29477-505