D'Alessandro L A, Hoehme S, Henney A, Drasdo D, Klingmüller U
Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), INF 280, 69120 Heidelberg, Germany.
Interdisciplinary Centre for Bioinformatics (IZBI), University of Leipzig, Germany.
Prog Biophys Mol Biol. 2015 Jan;117(1):78-86. doi: 10.1016/j.pbiomolbio.2014.11.005. Epub 2014 Nov 26.
Biological responses are determined by information processing at multiple and highly interconnected scales. Within a tissue the individual cells respond to extracellular stimuli by regulating intracellular signaling pathways that in turn determine cell fate decisions and influence the behavior of neighboring cells. As a consequence the cellular responses critically impact tissue composition and architecture. Understanding the regulation of these mechanisms at different scales is key to unravel the emergent properties of biological systems. In this perspective, a multidisciplinary approach combining experimental data with mathematical modeling is introduced. We report the approach applied within the Virtual Liver Network to analyze processes that regulate liver functions from single cell responses to the organ level using a number of examples. By facilitating interdisciplinary collaborations, the Virtual Liver Network studies liver regeneration and inflammatory processes as well as liver metabolic functions at multiple scales, and thus provides a suitable example to identify challenges and point out potential future application of multi-scale systems biology.
生物反应由多个高度互联尺度上的信息处理所决定。在组织内，单个细胞通过调节细胞内信号通路对细胞外刺激做出反应，这些信号通路反过来决定细胞命运决策并影响相邻细胞的行为。因此，细胞反应对组织组成和结构有着至关重要的影响。理解这些机制在不同尺度上的调控是揭示生物系统涌现特性的关键。从这个角度出发，引入了一种将实验数据与数学建模相结合的多学科方法。我们报告了在虚拟肝脏网络中应用的方法，通过多个例子分析从单细胞反应到器官水平调节肝脏功能的过程。通过促进跨学科合作，虚拟肝脏网络在多个尺度上研究肝脏再生、炎症过程以及肝脏代谢功能，从而为识别挑战和指出多尺度系统生物学未来潜在应用提供了一个合适的例子。
