IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0039407.html
   My bibliography  Save this article

Bottom-Up Engineering of Biological Systems through Standard Bricks: A Modularity Study on Basic Parts and Devices

Author

Listed:
  • Lorenzo Pasotti
  • Nicolò Politi
  • Susanna Zucca
  • Maria Gabriella Cusella De Angelis
  • Paolo Magni

Abstract

Background: Modularity is a crucial issue in the engineering world, as it enables engineers to achieve predictable outcomes when different components are interconnected. Synthetic Biology aims to apply key concepts of engineering to design and construct new biological systems that exhibit a predictable behaviour. Even if physical and measurement standards have been recently proposed to facilitate the assembly and characterization of biological components, real modularity is still a major research issue. The success of the bottom-up approach strictly depends on the clear definition of the limits in which biological functions can be predictable. Results: The modularity of transcription-based biological components has been investigated in several conditions. First, the activity of a set of promoters was quantified in Escherichia coli via different measurement systems (i.e., different plasmids, reporter genes, ribosome binding sites) relative to an in vivo reference promoter. Second, promoter activity variation was measured when two independent gene expression cassettes were assembled in the same system. Third, the interchangeability of input modules (a set of constitutive promoters and two regulated promoters) connected to a fixed output device (a logic inverter) expressing GFP was evaluated. The three input modules provide tunable transcriptional signals that drive the output device. If modularity persists, identical transcriptional signals trigger identical GFP outputs. To verify this, all the input devices were individually characterized and then the input-output characteristic of the logic inverter was derived in the different configurations. Conclusions: Promoters activities (referred to a standard promoter) can vary when they are measured via different reporter devices (up to 22%), when they are used within a two-expression-cassette system (up to 35%) and when they drive another device in a functionally interconnected circuit (up to 44%). This paper provides a significant contribution to the study of modularity limitations in building biological systems by providing useful data on context-dependent variability of biological components.

Suggested Citation

  • Lorenzo Pasotti & Nicolò Politi & Susanna Zucca & Maria Gabriella Cusella De Angelis & Paolo Magni, 2012. "Bottom-Up Engineering of Biological Systems through Standard Bricks: A Modularity Study on Basic Parts and Devices," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-10, July.
    • Handle: RePEc:plo:pone00:0039407
    DOI: 10.1371/journal.pone.0039407
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0039407
    Download Restriction: no
    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0039407&type=printable
    Download Restriction: no
    File URL: https://libkey.io/10.1371/journal.pone.0039407?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Baojun Wang & Richard I Kitney & Nicolas Joly & Martin Buck, 2011. "Engineering modular and orthogonal genetic logic gates for robust digital-like synthetic biology," Nature Communications, Nature, vol. 2(1), pages 1-9, September.
    2. Michael B. Elowitz & Stanislas Leibler, 2000. "A synthetic oscillatory network of transcriptional regulators," Nature, Nature, vol. 403(6767), pages 335-338, January.
    3. Roberta Kwok, 2010. "Five hard truths for synthetic biology," Nature, Nature, vol. 463(7279), pages 288-290, January.
    4. Drew Endy, 2005. "Foundations for engineering biology," Nature, Nature, vol. 438(7067), pages 449-453, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Weiyue Ji & Handuo Shi & Haoqian Zhang & Rui Sun & Jingyi Xi & Dingqiao Wen & Jingchen Feng & Yiwei Chen & Xiao Qin & Yanrong Ma & Wenhan Luo & Linna Deng & Hanchi Lin & Ruofan Yu & Qi Ouyang, 2013. "A Formalized Design Process for Bacterial Consortia That Perform Logic Computing," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-9, February.
    2. Mario A Marchisio & Jörg Stelling, 2011. "Automatic Design of Digital Synthetic Gene Circuits," PLOS Computational Biology, Public Library of Science, vol. 7(2), pages 1-13, February.
    3. Nasimul Noman & Taku Monjo & Pablo Moscato & Hitoshi Iba, 2015. "Evolving Robust Gene Regulatory Networks," PLOS ONE, Public Library of Science, vol. 10(1), pages 1-21, January.
    4. Javier Macia & Romilde Manzoni & Núria Conde & Arturo Urrios & Eulàlia de Nadal & Ricard Solé & Francesc Posas, 2016. "Implementation of Complex Biological Logic Circuits Using Spatially Distributed Multicellular Consortia," PLOS Computational Biology, Public Library of Science, vol. 12(2), pages 1-24, February.
    5. Nylund, Petra A. & Ferràs-Hernández, Xavier & Pareras, Luis & Brem, Alexander, 2022. "The emergence of entrepreneurial ecosystems based on enabling technologies: Evidence from synthetic biology," Journal of Business Research, Elsevier, vol. 149(C), pages 728-735.
    6. Jin Wang & Bo Huang & Xuefeng Xia & Zhirong Sun, 2006. "Funneled Landscape Leads to Robustness of Cell Networks: Yeast Cell Cycle," PLOS Computational Biology, Public Library of Science, vol. 2(11), pages 1-10, November.
    7. Avraham E Mayo & Yaakov Setty & Seagull Shavit & Alon Zaslaver & Uri Alon, 2006. "Plasticity of the cis-Regulatory Input Function of a Gene," PLOS Biology, Public Library of Science, vol. 4(4), pages 1-1, March.
    8. Ankit Gupta & Mustafa Khammash, 2022. "Frequency spectra and the color of cellular noise," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Bottani, Samuel & Grammaticos, Basile, 2008. "A simple model of genetic oscillations through regulated degradation," Chaos, Solitons & Fractals, Elsevier, vol. 38(5), pages 1468-1482.
    10. Chih-Yuan Hsu & Bor-Sen Chen, 2016. "Systematic Design of a Metal Ion Biosensor: A Multi-Objective Optimization Approach," PLOS ONE, Public Library of Science, vol. 11(11), pages 1-16, November.
    11. Margherita Carletti & Malay Banerjee, 2019. "A Backward Technique for Demographic Noise in Biological Ordinary Differential Equation Models," Mathematics, MDPI, vol. 7(12), pages 1-16, December.
    12. Konstantinos I Papadimitriou & Guy-Bart V Stan & Emmanuel M Drakakis, 2013. "Systematic Computation of Nonlinear Cellular and Molecular Dynamics with Low-Power CytoMimetic Circuits: A Simulation Study," PLOS ONE, Public Library of Science, vol. 8(2), pages 1-24, February.
    13. Inés P Mariño & Alexey Zaikin & Joaquín Míguez, 2017. "A comparison of Monte Carlo-based Bayesian parameter estimation methods for stochastic models of genetic networks," PLOS ONE, Public Library of Science, vol. 12(8), pages 1-25, August.
    14. Zhdanov, Vladimir P., 2012. "Periodic perturbation of genetic oscillations," Chaos, Solitons & Fractals, Elsevier, vol. 45(5), pages 577-587.
    15. Dhiman, Aman & Poria, Swarup, 2018. "Allee effect induced diversity in evolutionary dynamics," Chaos, Solitons & Fractals, Elsevier, vol. 108(C), pages 32-38.
    16. Javier Santos-Moreno & Eve Tasiudi & Hadiastri Kusumawardhani & Joerg Stelling & Yolanda Schaerli, 2023. "Robustness and innovation in synthetic genotype networks," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    17. T. Ochiai & J. C. Nacher, 2007. "Stochastic analysis of autoregulatory gene expression dynamics," Mathematical and Computer Modelling of Dynamical Systems, Taylor & Francis Journals, vol. 14(4), pages 377-388, November.
    18. Thomas B. Kepler & Timothy C. Elston, 2001. "Stochasticity in Transcriptional Regulation: Origins, Consequences and Mathematical Representations," Working Papers 01-06-033, Santa Fe Institute.
    19. Luis Mier-y-Terán-Romero & Mary Silber & Vassily Hatzimanikatis, 2010. "The Origins of Time-Delay in Template Biopolymerization Processes," PLOS Computational Biology, Public Library of Science, vol. 6(4), pages 1-15, April.
    20. VAN DEN OORD, Ad & VAN WITTELOOSTUIJN, Arjen & DUYSTERS, Geert & GILSING, Victor, 2010. "The ecology of technology: An empirical study of US biotechnology patents from 1976 to 2003," ACED Working Papers 2010008, University of Antwerp, Faculty of Business and Economics.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0039407. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.