Synthesis of Nondeterministic Behavior in Recombinase-Based Genetic Circuits

Recombinases have been exploited in synthetic biology as a technique to engineer genetic circuits for various application tasks. Prior works mostly studied the construction of combinational or sequential circuits with deterministic behavior. Nevertheless, nondeterminism is ubiquitous in biochemical systems and is an essential resource to enable various biochemical processes, such as cell differentiation and pattern formation. In this work, we study the synthesis of nondeterministic recombinase-based genetics circuits specified by a Boolean relation. We develop methods to create nondeterminism and synthesize the intended nondeterministic circuit. The synthesis methodology is experimented to evaluate the effectiveness of DNA sequence length reduction in the constructed genetic circuits.

[1]  Jie-Hong Roland Jiang,et al.  Recombinase-based genetic circuit optimization , 2017, 2017 IEEE Biomedical Circuits and Systems Conference (BioCAS).

[2]  J. Liao,et al.  A synthetic gene–metabolic oscillator , 2005, Nature.

[3]  Franck Molina,et al.  Detection of pathological biomarkers in human clinical samples via amplifying genetic switches and logic gates , 2015, Science Translational Medicine.

[4]  Margaret C. M. Smith,et al.  Switching the polarity of a bacteriophage integration system , 2004, Molecular microbiology.

[5]  G. Church,et al.  Synthetic Gene Networks That Count , 2009, Science.

[6]  Timothy K Lu,et al.  Synthetic circuits integrating logic and memory in living cells , 2013, Nature Biotechnology.

[7]  G. Hatfull,et al.  Two-step site selection for serine-integrase-mediated excision: DNA-directed integrase conformation and central dinucleotide proofreading , 2008, Proceedings of the National Academy of Sciences.

[8]  T. Lu,et al.  Synthetic recombinase-based state machines in living cells , 2016, Science.

[9]  Arjun Raj,et al.  What's Luck Got to Do with It: Single Cells, Multiple Fates, and Biological Nondeterminism. , 2016, Molecular cell.

[10]  J. Keasling,et al.  Rapid metabolic pathway assembly and modification using serine integrase site-specific recombination , 2013, Nucleic acids research.

[11]  Tai-Yin Chiu,et al.  Logic Synthesis of Recombinase-Based Genetic Circuits , 2016 .

[12]  H. Nash.  Site-Specific Recombination : Integration , Excision , Resolution , and Inversion of Defined DNA Segments , 1999 .

[13]  Jie-Hong Roland Jiang,et al.  Interpolating functions from large Boolean relations , 2009, 2009 IEEE/ACM International Conference on Computer-Aided Design - Digest of Technical Papers.

[14]  J. Doudna,et al.  The new frontier of genome engineering with CRISPR-Cas9 , 2014, Science.