Teo Jonathan J Y, Sarpeshkar Rahul
Computational and Systems Biology Program at the Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
iScience. 2020 Oct 15;23(11):101688. doi: 10.1016/j.isci.2020.101688. eCollection 2020 Nov 20.
Biological circuits and systems within even a single cell need to be represented by large-scale feedback networks of nonlinear, stochastic, stiff, asynchronous, non-modular coupled differential equations governing complex molecular interactions. Thus, rational drug discovery and synthetic biological design is difficult. We suggest that a four-pronged interdisciplinary approach merging biology and electronics can help: (1) The mapping of biological circuits to electronic circuits via quantitatively exact schematics; (2) The use of existing electronic circuit software for hierarchical modeling, design, and analysis with such schematics; (3) The use of cytomorphic electronic hardware for rapid stochastic simulation of circuit schematics and associated parameter discovery to fit measured biological data; (4) The use of bio-electronic reporting circuits rather than bio-optical circuits for measurement. We suggest how these approaches can be combined to automate design, modeling, analysis, simulation, and quantitative fitting of measured data from a synthetic biological operational amplifier circuit in living microbial cells.
即使是单个细胞内的生物电路和系统,也需要用大规模的反馈网络来表示,这些网络由控制复杂分子相互作用的非线性、随机、刚性、异步、非模块化耦合微分方程组成。因此,合理的药物发现和合成生物学设计很困难。我们认为,将生物学和电子学相结合的四管齐下的跨学科方法会有所帮助:(1)通过定量精确的原理图将生物电路映射到电子电路;(2)使用现有的电子电路软件对这类原理图进行层次建模、设计和分析;(3)使用细胞形态电子硬件对电路原理图进行快速随机模拟,并发现相关参数以拟合实测生物学数据;(4)使用生物电子报告电路而非生物光学电路进行测量。我们提出了如何将这些方法结合起来,以实现对活微生物细胞中合成生物运算放大器电路的测量数据进行自动化设计、建模、分析、模拟和定量拟合。