Advertisement

Boolean Recombinase-Based Devices

Conference paper
  • 266 Downloads
Part of the Lecture Notes in Computer Science book series (LNCS, volume 11934)

Abstract

This paper relates to a central problem in synthetic biology, which is that of designing Recombinase-based biological devices by matching a functional specification expressed as a Boolean function. This task is challenging as exploring the space of possibilities is typically unfeasible, and therefore many non-trivial design alternatives remain unexplored. Also, the issue has been so far regarded mainly from a practical perspective and is still lacking of formal foundations on which the definition of algorithms for assisting the biologists in their design tasks can be based. In this work, we present the first formal study of the problem, and give a formal semantics for a family of Recombinase-based biological devices. We then exhibit a set of semantic properties leading to the definition of representative devices, a notion that allows one to express infinitely large classes of design possibilities in a finite way. Building on this, we then provide a terminating algorithm for generating representative devices for n-input Boolean functions. An open online database of 18M design solutions for 4-inputs devices generated with our method has been released at http://recombinator.lirmm.fr.

Keywords

Boolean devices Synthetic biology 

References

  1. 1.
    Astola, J., Stankovic, R.: Fundamentals of Switching Theory and Logic Design A Hands on Approach. Springer, Cham (2006).  https://doi.org/10.1007/0-387-30311-1CrossRefGoogle Scholar
  2. 2.
    Bischof, J., Maeda, R.K., Hediger, M., Karch, F., Basler, K.: An optimized transgenesis system for drosophila using germ-line-specific \(\varphi \)c31 integrases. Proc. Natl. Acad. Sci. 104(9), 3312–3317 (2007)CrossRefGoogle Scholar
  3. 3.
    Bonnet, J., Yin, P., Ortiz, M.E., Subsoontorn, P., Endy, D.: Amplifying genetic logic gates. Science 340(6132), 599–603 (2013)CrossRefGoogle Scholar
  4. 4.
    Chiu, T.Y., Jiang, J.H.R.: Logic synthesis of recombinase-based genetic circuits. Sci. Rep. 7(1), 12873 (2017)CrossRefGoogle Scholar
  5. 5.
    Dueber, J.E., Yeh, B.J., Chak, K., Lim, W.A.: Reprogramming control of an allosteric signaling switch through modular recombination. Science 301(5641), 1904–1908 (2003)CrossRefGoogle Scholar
  6. 6.
    Endy, D.: Foundations for engineering biology. Nature 438(7067), 449 (2005)CrossRefGoogle Scholar
  7. 7.
    Guiziou, S., Pérution-Kihli, G., Ulliana, F., Leclère, M., Bonnet, J.: Exploring the design space of recombinase logic circuits. bioRxiv (2019).  https://doi.org/10.1101/711374
  8. 8.
    Guiziou, S., Ulliana, F., Moreau, V., Leclère, M., Bonnet, J.: An automated design framework for multicellular recombinase logic. ACS Synth. Biol. 7(5), 1406–1412 (2018)CrossRefGoogle Scholar
  9. 9.
    Kumari, A., Pasini, P., Daunert, S.: Detection of bacterial quorum sensing n-acyl homoserine lactones in clinical samples. Anal. Bioanal. Chem. 391(5), 1619–1627 (2008)CrossRefGoogle Scholar
  10. 10.
    Nielsen, A.A., et al.: Genetic circuit design automation. Science 352(6281), aac7341 (2016)CrossRefGoogle Scholar
  11. 11.
    Wang, Y., Yau, Y.Y., Perkins-Balding, D., Thomson, J.G.: Recombinase technology: applications and possibilities. Plant Cell Rep. 30(3), 267–285 (2011).  https://doi.org/10.1007/s00299-010-0938-1CrossRefGoogle Scholar
  12. 12.
    Weinberg, B.H., et al.: Large-scale design of robust genetic circuits with multiple inputs and outputs for mammalian cells. Nat. Biotechnol. 35(5), 453 (2017)CrossRefGoogle Scholar
  13. 13.
    Win, M.N., Smolke, C.D.: Higher-order cellular information processing with synthetic RNA devices. Science 322(5900), 456–460 (2008)CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.LIRMM, CNRS UMR 5506University of MontpellierMontpellierFrance
  2. 2.CBS, INSERM U154, CNRS UMR 5048University of MontpellierMontpellierFrance
  3. 3.Department of BiologyUniversity of WashingtonSeattleUSA

Personalised recommendations