Otero-Muras Irene, Perez-Carrasco Ruben, Banga Julio R, Barnes Chris P
Computational Synthetic Biology Group. Institute for Integrative Systems Biology (UV, CSIC), Spanish National Research Council, 46980 Valencia, Spain.
Department of Life Sciences. Imperial College London, London, UK.
iScience. 2023 May 9;26(6):106836. doi: 10.1016/j.isci.2023.106836. eCollection 2023 Jun 16.
Recent advances in synthetic biology are enabling exciting technologies, including the next generation of biosensors, the rational design of cell memory, modulated synthetic cell differentiation, and generic multifunctional biocircuits. These novel applications require the design of gene circuits leading to sophisticated behaviors and functionalities. At the same time, designs need to be kept minimal to avoid compromising cell viability. Bifurcation theory addresses such challenges by associating circuit dynamical properties with molecular details of its design. Nevertheless, incorporating bifurcation analysis into automated design processes has not been accomplished yet. This work presents an optimization-based method for the automated design of synthetic gene circuits with specified bifurcation diagrams that employ minimal network topologies. Using this approach, we designed circuits exhibiting the mushroom bifurcation, distilled the most robust topologies, and explored its multifunctional behavior. We then outline potential applications in biosensors, memory devices, and synthetic cell differentiation.
合成生物学的最新进展催生了令人兴奋的技术，包括下一代生物传感器、细胞记忆的合理设计、调控合成细胞分化以及通用多功能生物电路。这些新颖的应用需要设计出能产生复杂行为和功能的基因电路。与此同时，设计需要保持简洁，以避免损害细胞活力。分岔理论通过将电路动力学特性与其设计的分子细节相关联来应对此类挑战。然而，将分岔分析纳入自动化设计过程尚未实现。这项工作提出了一种基于优化的方法，用于自动设计具有特定分岔图且采用最小网络拓扑结构的合成基因电路。利用这种方法，我们设计了呈现蘑菇状分岔的电路，提炼出最稳健的拓扑结构，并探索了其多功能行为。然后，我们概述了在生物传感器、存储设备和合成细胞分化方面的潜在应用。
