Week8-Identifying Emergent Properties-From Model Predictions to Experiments-Ultrasensitivity-Robustness- Scaffolds

12.A Integrated Reasoning: Merging Bottom Up and Top Down Reasoning

1. Identifying Emergent Properties涌现性: Bistability双稳性
   What is an Emergent Property ?
   An emergent property is a property the system as whole possesses but cannot be attributed to any individual component of the system. Emergent properties of cell biological systems include bistability, ultrasensitivity 超敏性robustness ...probably many others waiting to be discovered.

What is Bistability ?
Bistability is the ability of a system to exist in two stable states i.e. the system can switch between states. Often the switching is stimulus driven这种转换由刺激因素诱发 and hence enables change in state of the cell改变细胞的状态.

Why is this Integrated Reasoning综合推理 ?
The ability to use ODE based modeling to identify bistability as a property of a positive feedback loop allows us to enumerate the capability of a part of a network identified by topological analysis.这种工作使我们能够通过拓扑分析来了解整个网络的特性

2. Dynamical Analysis of a Bistable System-如何Set up an ODE Model？

Bhalla & Iyengar ( 1999) Science 283:381

1） Identify the reactions involved in the model
2） Parameterize the reactions-find reaction rates反应速率, concentrations of reactions反应物浓度 (most of these proteins had been purified提纯 from tissues so
with some work Upi was able to find/estimate
parameters)
3） Constrain the model in a modular fashion data用相应的标准来限制这个模型

constrain the model by running test simulations to see if the model behavior is similar to what been seen in experiments. Two examples are shown。
Recommendation: Don’t tweak (change) parameters so that simulations exactly fit the experiments –We should Note the differences but run the model with the “most reasonably” selected parameters

The appropriate place to change parameters is during systematic parameter variation系统中的参数变动. This is a meaningful exercise as it can tell us the “best” set of parameters for an observed experimental profile.

4）Ensure that during the simulations the model obeys
a. mass conservation质量守恒。要求反应开始前反应物质的质量等于反应结束后物质的质量，
b. microscopic reversibility微观可逆性。要求所有正向反应的产物量与所有逆向反应的产物量相等

12.B From Model Predictions to Experiments

Bhalla, Ram Iyengar (2002) Science 297:1018

13.A Emergent Properties: Ultrasensitivity

1. What is Ultrasensitivity超敏性 ?
   “We shall use the term "ultrasensitivity" to describe an output response that is more
   sensitive to change in stimulus than the hyperbolic (Michaelis-Menten) equation.”对刺激做出相对于米式方程的预测更敏感变化的输出反应
   From Goldbeter & Koshland
2. 为什么会出现超敏性？
   当两种酶作用于同一底物，单个的酶对底物的作用都遵从米氏方程，但是当两者加起来之后，就会呈现超敏性。

13.B Emergent Properties: Robustness

1. What is Robustness?
   Robustness is, the ability to maintain unaltered function even when the structure
   such as topology of a network defined by edges or core characteristics of a system
   defined by kinetic parameters is altered or when the system changes due to
   environmental stimulus.
2. Why is Robustness an Emergent Property?
   The function that is maintained without change is a systems level function. What
   changes is the characteristics of individual components . So by its very nature
   robustness is a systems level property that arises from the interactions between
   components of a system – an emergent property
3. Scaffolds支架蛋白 , Adaptors and Anchoring Proteins

14.A Case Study : A Circadian Oscillator 昼夜节律振荡器in Bacteria

14.B Cell Spreading Model