Frontiers in Bioengineering and Biotechnology (Aug 2020)

Computer-Aided Whole-Cell Design: Taking a Holistic Approach by Integrating Synthetic With Systems Biology

  • Lucia Marucci,
  • Lucia Marucci,
  • Lucia Marucci,
  • Matteo Barberis,
  • Matteo Barberis,
  • Matteo Barberis,
  • Jonathan Karr,
  • Oliver Ray,
  • Paul R. Race,
  • Paul R. Race,
  • Miguel de Souza Andrade,
  • Miguel de Souza Andrade,
  • Claire Grierson,
  • Claire Grierson,
  • Stefan Andreas Hoffmann,
  • Sophie Landon,
  • Sophie Landon,
  • Elibio Rech,
  • Joshua Rees-Garbutt,
  • Joshua Rees-Garbutt,
  • Richard Seabrook,
  • William Shaw,
  • Christopher Woods,
  • Christopher Woods

DOI
https://doi.org/10.3389/fbioe.2020.00942
Journal volume & issue
Vol. 8

Abstract

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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.

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