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Methods in molecular biology (Clifton, N.J.)
2021;2229 267-291.

Prediction of Cellular Burden with Host-Circuit Models.

Evangelos-Marios Nikolados, Andrea Y Weiße, Diego A Oyarzún
Author Information
  1. Evangelos-Marios Nikolados: School of Biological Sciences, University of Edinburgh, Edinburgh, UK.
  2. Andrea Y Weiße: School of Informatics, University of Edinburgh, Edinburgh, UK.
  3. Diego A Oyarzún: School of Biological Sciences, University of Edinburgh, Edinburgh, UK. d.oyarzun@ed.ac.uk.
PMID: 33405227 DOI: 10.1007/978-1-0716-1032-9_13

Abstract

Heterologous gene expression draws resources from host cells. These resources include vital components to sustain growth and replication, and the resulting cellular burden is a widely recognized bottleneck in the design of robust circuits. In this tutorial we discuss the use of computational models that integrate gene circuits and the physiology of host cells. Through various use cases, we illustrate the power of host-circuit models to predict the impact of design parameters on both burden and circuit functionality. Our approach relies on a new generation of computational models for microbial growth that can flexibly accommodate resource bottlenecks encountered in gene circuit design. Adoption of this modeling paradigm can facilitate fast and robust design cycles in synthetic biology.

Keywords

Cellular burden Gene circuit design Growth models Resource allocation Synthetic biology Whole-cell modeling

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MeSH Term

Bacteria
Bacterial Physiological Phenomena
Bacterial Proteins
Gene Expression
Gene Regulatory Networks
Genes, Synthetic
Models, Biological
Synthetic Biology
Systems Biology

Chemicals

Bacterial Proteins
Journal Article
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