ArticleNucleic acids research2011
Computational design of synthetic regulatory networks from a genetic library to characterize the designability of dynamical behaviors.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Automatic design of gene regulatory mechanisms for spatial pattern formation.NPJ systems biology and applications · 2024Article
- Repurposing the mammalian RNA-binding protein Musashi-1 as an allosteric translation repressor in bacteria.eLife · 2024Article
- Gene regulation by a protein translation factor at the single-cell level.PLoS computational biology · 2022Article
- Microbial production of small peptide: pathway engineering and synthetic biology.Microbial biotechnology · 2021Review
- Towards an Aspect-Oriented Design and Modelling Framework for Synthetic Biology.Processes (Basel, Switzerland) · 2018Article
- A computational method for the investigation of multistable systems and its application to genetic switches.BMC systems biology · 2016Article
- Process-based design of dynamical biological systems.Scientific reports · 2016Article
- Design Principles of Biological Oscillators through Optimization: Forward and Reverse Analysis.PloS one · 2016Article
- Atypical PKCs in memory maintenance: the roles of feedback and redundancy.Learning & memory (Cold Spring Harbor, N.Y.) · 2015Article
- Synthesizing genetic sequential logic circuit with clock pulse generator.BMC systems biology · 2014Article
- Bridging the gap: a roadmap to breaking the biological design barrier.Frontiers in bioengineering and biotechnology · 2014Review
- Systematic design methodology for robust genetic transistors based on I/O specifications via promoter-RBS libraries.BMC systems biology · 2013Article
- Computational design of genomic transcriptional networks with adaptation to varying environments.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Automatic design of synthetic gene circuits through mixed integer non-linear programming.PloS one · 2012Article
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Authors and funding
3 authors.
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Abstract
The engineering of synthetic gene networks has mostly relied on the assembly of few characterized regulatory elements using rational design principles. It is of outmost importance to analyze the scalability and limits of such a design workflow. To analyze the design capabilities of libraries of regulatory elements, we have developed the first automated design approach that combines such elements to search the genotype space associated to a given phenotypic behavior. Herein, we calculated the designability of dynamical functions obtained from circuits assembled with a given genetic library. By designing circuits working as amplitude filters, pulse counters and oscillators, we could infer new mechanisms for such behaviors. We also highlighted the hierarchical design and the optimization of the interface between devices. We dissected the functional diversity of a constrained library and we found that even such libraries can provide a rich variety of behaviors. We also found that intrinsic noise slightly reduces the designability of digital circuits, but it increases the designability of oscillators. Finally, we analyzed the robust design as a strategy to counteract the evolvability and noise in gene expression of the engineered circuits within a cellular background, obtaining mechanisms for robustness through non-linear negative feedback loops.
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