Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.
PLoS Comput Biol. 2013;9(8):e1003163. doi: 10.1371/journal.pcbi.1003163. Epub 2013 Aug 8.
Biological regulatory systems face a fundamental tradeoff: they must be effective but at the same time also economical. For example, regulatory systems that are designed to repair damage must be effective in reducing damage, but economical in not making too many repair proteins because making excessive proteins carries a fitness cost to the cell, called protein burden. In order to see how biological systems compromise between the two tasks of effectiveness and economy, we applied an approach from economics and engineering called Pareto optimality. This approach allows calculating the best-compromise systems that optimally combine the two tasks. We used a simple and general model for regulation, known as integral feedback, and showed that best-compromise systems have particular combinations of biochemical parameters that control the response rate and basal level. We find that the optimal systems fall on a curve in parameter space. Due to this feature, even if one is able to measure only a small fraction of the system's parameters, one can infer the rest. We applied this approach to estimate parameters in three biological systems: response to heat shock and response to DNA damage in bacteria, and calcium homeostasis in mammals.
它们必须有效，但同时也要经济。例如，旨在修复损伤的调节系统必须有效地减少损伤，但也不能制造过多的修复蛋白，因为制造过多的蛋白会给细胞带来适应度成本，称为蛋白负担。为了了解生物系统在有效性和经济性这两个任务之间是如何妥协的，我们采用了经济学和工程学中的一种方法，称为帕累托最优。这种方法可以计算出最佳妥协系统，使这两个任务得到最佳组合。我们使用了一种简单而通用的调节模型，称为积分反馈，并表明最佳妥协系统具有控制响应速率和基础水平的特定生化参数组合。我们发现，最优系统落在参数空间的一条曲线上。由于这个特点，即使只能测量系统参数的一小部分，也可以推断出其余部分。我们将这种方法应用于估计三个生物系统中的参数：细菌对热休克和 DNA 损伤的反应，以及哺乳动物的钙稳态。
