Article

Cellular logic with orthogonal ribosomes

Mrc Harwell, Oxford, England, United Kingdom
Journal of the American Chemical Society (Impact Factor: 11.44). 01/2006; 127(50):17584-5. DOI: 10.1021/ja055338d
Source: PubMed

ABSTRACT The creation and use of unnatural molecules to control cellular function is a long standing goal of the chemical community, but in general, these efforts have been directed at finding molecules to inhibit or activate a particular molecular target or function, or to elicit a particular phenotype. Here we show that multiple unnatural molecules (orthogonal ribosomes) can be used combinatorially, in a single cell, to program Boolean logic functions. These experiments show how attention to the molecular specificity of noncovalent interactions between unnatural macromolecules allows the synthesis of complex function from the "bottom-up" in living matter.

1 Follower
 · 
94 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: It was previously thought that the proteins produced by ribosomes were dictated only by the sequences of the mRNAs they translated, however now it is apparent that subpopulations of ribosomes can have unique properties that influence the functions of the proteins they produce. Ribosomes have been engineered to discriminate between different mRNA templates or with unique decoding properties, and many new applications of unnatural ribosomes can be foreseen. In natural systems ribosomes with alternate protein and RNA composition have been shown to selectively translate specific mRNAs. As more is learned about ribosome structure and the mechanisms of translation, new opportunities to engineer ribosomes for applications in biotechnology and synthetic biology can be developed and new examples of ribosome-mediated regulation of translation are likely to emerge in nature.
    FEBS letters 02/2013; 587(8). DOI:10.1016/j.febslet.2013.02.032
  • Source
    The EMBO Journal 06/2011; 30(12):2312-24. DOI:10.1038/emboj.2011.160
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synthetic biology is a nascent technical discipline that seeks to enable the design and construction of novel biological systems to meet pressing societal needs. However, engineering biology still requires much trial and error because we lack effective approaches for connecting basic "parts" into higher-order networks that behave as predicted. Developing strategies for improving the performance and sophistication of our designs is informed by two overarching perspectives: "bottom-up" and "top-down" considerations. Using this framework, we describe a conceptual model for developing novel biological systems that function and interact with existing biological components in a predictable fashion. We discuss this model in the context of three topical areas: biochemical transformations, cellular devices and therapeutics, and approaches that expand the chemistry of life. Ten years after the construction of synthetic biology's first devices, the drive to look beyond what does exist to what can exist is ushering in an era of biology by design.
    BioMed Research International 11/2010; 2010(1110-7243):232016. DOI:10.1155/2010/232016