Quantitative Systems Biology to decipher design principles of a dynamic cell cycle network: the "Maximum Allowable mammalian Trade-Off-Weight" (MAmTOW).
Quantitative Systems Biology to decipher design principles of a dynamic cell cycle network: the "Maximum Allowable mammalian Trade-Off-Weight" (MAmTOW).
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DOI：
10.1038/s41540-017-0028-x
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发表时间：
2017
影响因子：
4
通讯作者：
Verbruggen P
中科院分区：
文献类型：
--
作者：
Barberis M;Verbruggen P
网络复杂性需要赋予细胞过程灵活性以及时响应各种动态信号，同时保证鲁棒性以保护细胞完整性免受扰动。细胞周期是这些过程的范例；在前一种情况下，它保持其频率和时间结构（尽管这些可能因细胞类型而异），但在后一种情况下，它会加速。细胞周期分子在时间和不同的细胞区室中共同作用，执行细胞类型特异性程序。引人注目的是，分子开关发生的时间是由复合体内多种蛋白质的丰度和化学计量控制的。然而，一次研究一个效应的传统方法不足以理解细胞周期转变中蛋白质复合物动力学的调节如何形成响应性，同时保持鲁棒性。为了克服这一缺点，我们提出了一种多学科方法，从新的角度获得哺乳动物细胞定量细胞周期动力学的系统级理解。通过提出先进的实验技术和专门的建模方法，我们提出了创新的策略(i)来测量体内绝对蛋白质浓度，（ii）来确定蛋白质剂量（例如改变的蛋白质丰度）和空间（de）调节如何影响相变的时间和鲁棒性。我们描述了一种方法，我们命名为“最大允许哺乳动物权衡重量”（MAmTOW），可以实现确定哺乳动物细胞中基因拷贝数的上限。这些方面，目前的系统生物学方法没有涵盖，是生成精确计算模型和识别（子）网络中心节点的基本要求，这些节点是大量病理条件的基础。
Network complexity is required to lend cellular processes flexibility to respond timely to a variety of dynamic signals, while simultaneously warranting robustness to protect cellular integrity against perturbations. The cell cycle serves as a paradigm for such processes; it maintains its frequency and temporal structure (although these may differ among cell types) under the former, but accelerates under the latter. Cell cycle molecules act together in time and in different cellular compartments to execute cell type-specific programs. Strikingly, the timing at which molecular switches occur is controlled by abundance and stoichiometry of multiple proteins within complexes. However, traditional methods that investigate one effector at a time are insufficient to understand how modulation of protein complex dynamics at cell cycle transitions shapes responsiveness, yet preserving robustness. To overcome this shortcoming, we propose a multidisciplinary approach to gain a systems-level understanding of quantitative cell cycle dynamics in mammalian cells from a new perspective. By suggesting advanced experimental technologies and dedicated modeling approaches, we present innovative strategies (i) to measure absolute protein concentration in vivo, and (ii) to determine how protein dosage, e.g., altered protein abundance, and spatial (de)regulation may affect timing and robustness of phase transitions. We describe a method that we name “Maximum Allowable mammalian Trade–Off–Weight” (MAmTOW), which may be realized to determine the upper limit of gene copy numbers in mammalian cells. These aspects, not covered by current systems biology approaches, are essential requirements to generate precise computational models and identify (sub)network-centered nodes underlying a plethora of pathological conditions.
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影响因子：
--
作者：
Sasabe M;Shintani S;Kintaka R;Kaizu K;Makanae K;Moriya H
通讯作者：
Moriya H
影响因子：
--
作者：
Bartfeld S;Hess S;Bauer B;Machuy N;Ogilvie LA;Schuchhardt J;Meyer TF
通讯作者：
Meyer TF
影响因子：
5.1
作者：
Arendt, Thomas
通讯作者：
Arendt, Thomas
影响因子：
--
作者：
Crivellaro, Sabrina;Panuzzo, Cristina;Morotti, Alessandro
通讯作者：
Morotti, Alessandro
影响因子：
9.3
作者：
Barr AR;Heldt FS;Zhang T;Bakal C;Novák B
通讯作者：
Novák B