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

TL;DR

This paper discusses how integrating multiscale whole-cell models with synthetic biology can revolutionize design-build-test cycles, enabling more precise, automated, and modular engineering of biological systems.

Contribution

It presents a perspective on using comprehensive whole-cell models to enhance synthetic biology design processes and discusses challenges and opportunities for implementation.

Findings

Whole-cell models can improve design accuracy and efficiency.

Case studies demonstrate potential applications in genome minimization and cell-free systems.

Challenges include model complexity and data integration.

Abstract

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.