12.A Integrated Reasoning: Merging Bottom Up and Top Down Reasoning
- Identifying Emergent Properties涌現(xiàn)性: Bistability雙穩(wěn)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這種轉(zhuǎn)換由刺激因素誘發(fā) and hence enables change in state of the cell改變細(xì)胞的狀態(tài).
Why is this Integrated Reasoning綜合推理 ?
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.這種工作使我們能夠通過拓?fù)浞治鰜砹私庹麄€網(wǎng)絡(luò)的特性
- Dynamical Analysis of a Bistable System-如何Set up an ODE Model盏筐？
Bhalla & Iyengar ( 1999) Science 283:381
1） Identify the reactions involved in the model
2） Parameterize the reactions-find reaction rates反應(yīng)速率, concentrations of reactions反應(yīng)物濃度 (most of these proteins had been purified提純 from tissues so
with some work Upi was able to find/estimate
parameters)
3） Constrain the model in a modular fashion data用相應(yīng)的標(biāo)準(zhǔn)來限制這個模型
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腮出。
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系統(tǒng)中的參數(shù)變動. 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質(zhì)量守恒掉蔬。要求反應(yīng)開始前反應(yīng)物質(zhì)的質(zhì)量等于反應(yīng)結(jié)束后物質(zhì)的質(zhì)量属韧，
b. microscopic reversibility微觀可逆性斤葱。要求所有正向反應(yīng)的產(chǎn)物量與所有逆向反應(yīng)的產(chǎn)物量相等
12.B From Model Predictions to Experiments
Bhalla, Ram Iyengar (2002) Science 297:1018
13.A Emergent Properties: Ultrasensitivity
- 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.”對刺激做出相對于米式方程的預(yù)測更敏感變化的輸出反應(yīng)
From Goldbeter & Koshland - 為什么會出現(xiàn)超敏性冀膝？
當(dāng)兩種酶作用于同一底物酷麦，單個的酶對底物的作用都遵從米氏方程，但是當(dāng)兩者加起來之后否淤，就會呈現(xiàn)超敏性悄但。
13.B Emergent Properties: Robustness
- 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. - 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 - Scaffolds支架蛋白 , Adaptors and Anchoring Proteins
