Engineering Biology
Volume 1, Issue 2, December 2017
Volumes & issues:
Volume 1, Issue 2
December 2017
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- Author(s): Lionel J. Clarke
- Source: Engineering Biology, Volume 1, Issue 2, p. 66 –70
- DOI: 10.1049/enb.2017.0022
- Type: Article
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Drawing comparisons with the study of scientific revolutions by Thomas Kuhn over 50 years ago it is possible to frame synthetic biology as a new paradigm, approaching biology and its potential for redesign from an engineering and information management standpoint. This may help relate it to current thinking about potentially revolutionary future developments stemming from the recent and very rapidly progressing convergence of relevant technologies. However, striking differences from Kuhn's historic examples may also be noted – not only a greater awareness today of potential impacts that highlights the importance of explicitly incorporating broader issues of responsibility and governance but also the rapid growth in numbers of new researchers and entrepreneurs to the field globally which could accelerate the paradigm-shift process. The UK Synthetic Biology Roadmap 2012 and subsequent 2016 Strategy set out to develop a mechanism to respond nationally to this wider perspective, and examples, both UK and global, are drawn upon to help assess current progress towards the realisation of an ‘engineering biology’ paradigm.
Synthetic biology UK: progress, paradigms and prospects
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- Author(s): Elise Cachat ; Weijia Liu ; Jamie A. Davies
- Source: Engineering Biology, Volume 1, Issue 2, p. 71 –76
- DOI: 10.1049/enb.2017.0013
- Type: Article
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This study reports a proof-of-concept study as a step toward synthetic-biological morphogenesis of tissues. Events in normal animal development usually follow the sequence: patterning → differential gene expression → morphogenesis. A synthetic biological approach to development might follow a similar sequence, with each stage under the control of synthetic biological modules. The authors have constructed and published a synthetic module that drives self-organised patterning of mammalian cell populations into patches of different cell types. Here, as a proof of concept, they extend the self-patterning module with a morphogenetic effector that drives elective cell death in just one cell type. The result is a self-constructing pattern of two cell types, one of which can be selectively eliminated to leave remaining cells as a monolayer with a net-like structure. This simple device demonstrates and validates the idea of coupling synthetic biological morphogenetic effectors to synthetic biological patterning devices. It opens the path to engineering more sophisticated structures and, perhaps eventually, tissues.
- Author(s): Konstantinos Markakis ; Aitor De Las Heras ; Alistair Elfick
- Source: Engineering Biology, Volume 1, Issue 2, p. 77 –85
- DOI: 10.1049/enb.2017.0002
- Type: Article
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Characterisation of promoters, repressors, enhancers and so on, is not only essential for unravelling the inner workings of gene regulation, but also to enable the rational engineering of novel synthetic elements. Each putative regulatory region requires experimental assessment across a range of chassis and growth conditions, in order to be categorised as a fully defined functional element. In most studies, promoter activity is represented as the magnitude of a reporter signal, usually fluorescence, normalised to the biomass, as given by the optical density (OD). Such experimental values are often obtained from a coupled time-series experiment. Applying simple mathematical reasoning, a tool that describes promoter activity at each time point has been implemented. Protein expression and maturation, are modelled as first-order differential equations, taking into account the degradation and maturation rates which need to be known in advance. The promoter activity is then expressed based on the measured values of fluorescence and OD with a formula derived by mathematical manipulations of the defined quantities and the differential equations that comprise the model. Continuous expressions for fluorescence and OD are obtained from Gaussian process regression. Validation of the tool with experimental data from several constructs showed the expected behaviour of promoter activities.
- Author(s): Abhishek Deshpande and Thomas E. Ouldridge
- Source: Engineering Biology, Volume 1, Issue 2, p. 86 –99
- DOI: 10.1049/enb.2017.0017
- Type: Article
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Retroactivity arises when the coupling of a molecular network to a downstream network results in signal propagation back from to . The phenomenon represents a breakdown in modularity of biochemical circuits and hampers the rational design of complex functional networks. Considering simple models of signal-transduction architectures, the authors demonstrate the strong dependence of retroactivity on the properties of the upstream system, and explore the cost and efficacy of fuel-consuming insulating motifs that can mitigate retroactive effects. They find that simple insulating motifs can suppress retroactivity at a low fuel cost by coupling only weakly to the upstream system . However, this design approach reduces the signalling network's robustness to perturbations from leak reactions, and potentially compromises its ability to respond to rapidly varying signals.
- Author(s): Stefan Claesen ; Anna Stone ; Mark van Rossum ; Richard I. Kitney
- Source: Engineering Biology, Volume 1, Issue 2, p. 100 –102
- DOI: 10.1049/enb.2017.0019
- Type: Article
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100
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Synthetic biology, particularly in relation to characterisation experiments relating to the description of bio-parts frequently involves the use of a wide range of equipment, including, for example, plate reader's, flow cytometers, and mass spectrometers. This equipment is often from multiple manufacturers. The study describes broker technology that has been developed which has the ability to connect multiple types of equipment into a common information environment; the connectivity from the databases and equipment is achieved using Visbion's ‘cube’ technology that involves military specification encryption for data security. The broker technology uses a new, developing standard, Digital Imaging and Communication in Medicine (DICOM)-SB, that is based on the highly successful international standard for biomedicine, DICOM. The broker uses a version of the DICOM data model that has been specifically designed for synthetic biology and, in particular, characterisation data.
Synthetic self-patterning and morphogenesis in mammalian cells: a proof-of-concept step towards synthetic tissue development
Analytical approach for the calculation of promoter activities based on fluorescent protein expression data
High rates of fuel consumption are not required by insulating motifs to suppress retroactivity in biochemical circuits
Comprehensive web-based broker for bio-technology design and manufacturing
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