Abstract
Mathematical models and synthetic gene circuits are powerful tools to develop novel treatments for patients with drug-resistant infections and cancers. Mathematical modeling guides the rational design of synthetic gene circuits. These systems are then assembled into unified constructs from existing and/or modified genetic components from a range of organisms. In this chapter, we describe modeling tools for the design and characterization of chemical- and light-inducible synthetic gene circuits in different organisms and highlight how synthetic gene circuits are advancing biomedical research. Specifically, we demonstrate how these quantitative model systems are being used to study drug resistance in microbes and to probe the spatial–temporal dimensions of cancer in mammalian cells.
Highlights
A primary goal of synthetic biology is to rationally design and engineer synthetic gene circuits as tools to advance basic research [1, 2], optimize the production of chemicals or biofuels [3, 4], build biocomputational systems [5], and enhance clinical therapeutics [6]
Mathematical models and synthetic gene circuits have established that the architecture of the gene network modulates gene expression noise [14]
The pleiotropic drug resistance (PDR) network was recapitulated in mathematical and synthetic gene circuit models that demonstrated that the network architecture is optimized for drug resistance, with gene expression noise making important contributions to fitness during drug treatment
Summary
A primary goal of synthetic biology is to rationally design and engineer synthetic gene circuits as tools to advance basic research [1, 2], optimize the production of chemicals or biofuels [3, 4], build biocomputational systems [5], and enhance clinical therapeutics [6]. The fast temporal and single-cell spatial resolutions that light provides as a stimulus for gene circuits is unmatched; chemical stimulus regulates transcription on longer timescales and at a cell-population level. Like their gene circuit predecessors, optogenetic gene circuits can be used to control functional proteins. This chapter describes the construction and characterization of synthetic gene circuits in yeast and mammalian cells (Section 2) and optogenetic gene circuits in mammalian cells (Section 3) with various transcriptional network architectures, along with their applications in biomedical research. The mathematical approaches to model synthetic and optogenetic gene circuits are discussed
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