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Computer-Aided Whole-Cell Design: Taking a Holistic Approach by Integrating Synthetic With Systems Biology
Frontiers in Bioengineering and Biotechnology ( IF 5.7 ) Pub Date : 2020-08-07 , DOI: 10.3389/fbioe.2020.00942
Lucia Marucci 1, 2, 3 , Matteo Barberis 4, 5, 6 , Jonathan Karr 7 , Oliver Ray 8 , Paul R Race 3, 9 , Miguel de Souza Andrade 10, 11 , Claire Grierson 3, 12 , Stefan Andreas Hoffmann 13 , Sophie Landon 1, 3 , Elibio Rech 10 , Joshua Rees-Garbutt 3, 12 , Richard Seabrook 14 , William Shaw 15 , Christopher Woods 3, 16
Affiliation  

Computer-aided design (CAD) for synthetic biology promises to accelerate the rational and robust engineering of biological systems. It requires both detailed and quantitative mathematical and experimental models of the processes to (re)design biology, and software and tools for genetic engineering and DNA assembly. Ultimately, the increased precision in the design phase will have a dramatic impact on the production of designer cells and organisms with bespoke functions and increased modularity. CAD strategies require quantitative models of cells that can capture multiscale processes and link genotypes to phenotypes. Here, we present a perspective on how whole-cell, multiscale models could transform design-build-test-learn cycles in synthetic biology. We show how these models could significantly aid in the design and learn phases while reducing experimental testing by presenting case studies spanning from genome minimization to cell-free systems. We also discuss several challenges for the realization of our vision. The possibility to describe and build whole-cells in silico offers an opportunity to develop increasingly automatized, precise and accessible CAD tools and strategies.

中文翻译:

计算机辅助全细胞设计:通过将合成与系统生物学相结合采取整体方法

用于合成生物学的计算机辅助设计 (CAD) 有望加速生物系统的合理和稳健工程。它需要详细和定量的数学和实验模型来(重新)设计生物学,以及用于基因工程和 DNA 组装的软件和工具。最终,设计阶段精度的提高将对具有定制功能和更高模块化的设计细胞和生物体的生产产生巨大影响。CAD 策略需要能够捕捉多尺度过程并将基因型与表型联系起来的细胞定量模型。在这里,我们提出了关于全细胞多尺度模型如何改变合成生物学中的设计-构建-测试-学习周期的观点。我们展示了这些模型如何通过展示从基因组最小化到无细胞系统的案例研究,在减少实验测试的同时显着帮助设计和学习阶段。我们还讨论了实现我们愿景的几个挑战。在计算机中描述和构建全细胞的可能性为开发日益自动化、精确和可访问的 CAD 工具和策略提供了机会。
更新日期:2020-08-07
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