title: Tools and Principles for Microbial Gene Circuit Engineering.
abstract: Synthetic biologists aim to construct novel genetic circuits with useful applications through rational design and forward engineering. Given the complexity of signal processing that occurs in natural biological systems, engineered microbes have the potential to perform a wide range of desirable tasks that require sophisticated computation and control. Realising this goal will require accurate predictive design of complex synthetic gene circuits and accompanying large sets of quality modular and orthogonal genetic parts. Here we present a current overview of the versatile components and tools available for engineering gene circuits in microbes, including recently developed RNA-based tools that possess large dynamic ranges and can be easily programmed. We introduce design principles that enable robust and scalable circuit performance such as insulating a gene circuit against unwanted interactions with its context, and we describe efficient strategies for rapidly identifying and correcting causes of failure and fine-tuning circuit characteristics.
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom; School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, United Kingdom.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Bradley
authors.affiliation: Department of Life Sciences, Faculty of Natural Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
authors.forename: Martin
authors.initials: M
authors.lastname: Buck
authors.affiliation: School of Biological Sciences, University of Edinburgh, Edinburgh EH9 3FF, United Kingdom; Centre for Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3FF, United Kingdom. Electronic address: Baojun.Wang@ed.ac.uk.
authors.forename: Baojun
authors.initials: B
authors.lastname: Wang
mesh_terms: D053263:Gene Regulatory Networks; D018390:Gene Targeting / Q000379:methods*; D005818:Genetic Engineering / Q000379:methods*; D064349:Genome, Microbial; D058615:Synthetic Biology / Q000379:methods*
keywords: engineering tools; gene circuit; modularity and orthogonality; synthetic biology; transcriptional and translational control