Systems Biology of Signal Transduction, DKFZ-ZMBH Alliance, German Cancer Research Center, Heidelberg, Germany.
J Intern Med. 2012 Feb;271(2):155-65. doi: 10.1111/j.1365-2796.2011.02492.x.
Complex intracellular signalling networks integrate extracellular signals and convert them into cellular responses. In cancer cells, the tightly regulated and fine-tuned dynamics of information processing in signalling networks is altered, leading to uncontrolled cell proliferation, survival and migration. Systems biology combines mathematical modelling with comprehensive, quantitative, time-resolved data and is most advanced in addressing dynamic properties of intracellular signalling networks. Here, we introduce different modelling approaches and their application to medical systems biology, focusing on the identifiability of parameters in ordinary differential equation models and their importance in network modelling to predict cellular decisions. Two related examples are given, which include processing of ligand-encoded information and dual feedback regulation in erythropoietin (Epo) receptor signalling. Finally, we review the current understanding of how systems biology could foster the development of new treatment strategies in the context of lung cancer and anaemia.
复杂的细胞内信号网络整合细胞外信号，并将其转化为细胞反应。在癌细胞中，信号网络中信息处理的严格调控和精细调节的动力学发生改变，导致细胞不受控制的增殖、存活和迁移。系统生物学将数学建模与全面、定量、时间分辨的数据相结合，在解决细胞内信号网络的动态特性方面最为先进。在这里，我们介绍了不同的建模方法及其在医学系统生物学中的应用，重点介绍了常微分方程模型中参数的可识别性及其在网络建模中对预测细胞决策的重要性。给出了两个相关的例子，包括配体编码信息的处理和促红细胞生成素 (Epo) 受体信号中的双重反馈调节。最后，我们回顾了系统生物学如何在肺癌和贫血的背景下促进新的治疗策略的发展的现有理解。
