Computer-aided whole-cell design: taking a holistic approach by integrating synthetic with systems biology

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

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

22 Citations (Scopus)
174 Downloads (Pure)


Computer-aided design 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, 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. Computer-aided design strategies require quantitative representations of cells, able to 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, and we discuss several challenges for the realization of our vision. The possibility to describe and build in silico whole-cells offers an opportunity to develop increasingly automatized, precise and accessible computer-aided design tools and strategies throughout novel interdisciplinary collaborations.
Original languageEnglish
Article number942
Number of pages11
JournalFrontiers in Bioengineering and Biotechnology
Publication statusPublished - 7 Aug 2020

Structured keywords

  • Genome Design
  • BrisSynBio
  • Bristol BioDesign Institute
  • Engineering Mathematics Research Group


  • Whole-Cell Models
  • Synthetic Biology
  • Systems Biology
  • Bioengineering


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