DIVERSITY-BASED, MODEL-GUIDED CONSTRUCTION OF SYNTHETIC GENE NETWORKS WITH PREDICTED FUNCTIONS

By Tom Ellis, Xiao Wang, James J. Collins. Nature Biotechnology, 2009

482 citations recorded by the source corpus.

Engineering artificial gene networks from modular components is a major goal of synthetic biology. However, the construction of gene networks with predictable functions remains hampered by a lack of suitable components and the fact that assembled networks often require extensive, iterative retrofitting to work as intended. Here we present an approach that couples libraries of diversified components (synthesized with randomized nonessential sequence) with in silico modeling to guide predictable gene network construction without the need for post hoc tweaking. We demonstrate our approach in Saccharomyces cerevisiae by synthesizing regulatory promoter libraries and using them to construct feed-forward loop networks with different predicted input-output characteristics. We then expand our method to produce a synthetic gene network acting as a predictable timer, modifiable by component choice. We use this network to control the timing of yeast sedimentation, illustrating how the plug-and-play nature of our design can be readily applied to biotechnology.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/21302dbd47a34a816d47d0759ca22c24ec876f3d

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Citations in the corpus

Synthetic biology: applications come of age (2010, background): “To this end, there are ongoing synthetic biology efforts to create and characterize more reusable, biological control elements based on promoters for predictably tuning expression level”
Directed evolution: new parts and optimized function (2009, background): “Alternatively, having a library of tuned components already at hand allows rapid fine-tuning of circuit function, particularly with the aid of a validated mathematical model of the system [3].”
Genetic circuit design automation (2016, background): “These have begun to be integrated into biotechnological applications ( 34 , 35 ) — forexample,toimplementfeedbackcon-trol in a metabolic pathway ( 36 ).”
Biomolecular computing systems: principles, progress and potential (2012, methodology): “Thus, automated procedures have been proposed to translate abstract computations to molecular circuits using these components, using theoretical models and experimental measurements of these components in isolation 88,135–137 .”
A Synthetic Biology Framework for Programming Eukaryotic Transcription Functions (2012, background): “Within the circuit, sTF activators are ﬁrst transcribed from a previously described TetR-controlled GAL1 promoter (Ellis et al., 2009; Murphy et al., 2007), which is induced by anhydrotetracycline (ATc).”
125th Anniversary Review: Yeast Flocculation and Sedimentation in Brewing (2011, background): “Ellis et al. 16 designed a genetic network in which two genes mutually repressed each other and one of them re-pressed FLO1 .”