Synthetic Biology: An Emerging Engineering Discipline

Cheng, Allen A.; Lu, Timothy K.

doi:10.1146/annurev-bioeng-071811-150118

Cited by 211 publications

(165 citation statements)

References 134 publications

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“…1,2 To meet this promise, synthetic biology must become a rigorous engineering discipline based on rational and predictive design. [3][4][5][6] Modeling efforts within synthetic biology have so far focused on synthetic components and their interactions, where more detailed models have tried to refine these descriptions.…”

Section: Introductionmentioning

confidence: 99%

Towards a whole-cell modeling approach for synthetic biology

Purcell

Jain

Karr

et al. 2013

Chaos: An Interdisciplinary Journal of Nonlinear Science

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Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of wholecell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline. Synthetic biology aims to engineer synthetic genetic circuits to endow cells and organisms with the ability to address new applications, including the production of drugs and industrial products, the design of new therapeutics for human diseases, and the study of basic biological processes. Despite significant advances in the field over the last decade, the synthetic biology design cycle has been hampered by the lack of predictive models. In contrast, more established engineering disciplines, such as civil and electrical engineering can rely on rational design by using models that can capture the behavior of real-world systems with a high degree of accuracy. This is currently not the case for synthetic biology, as models are generally only able to make qualitative predictions about system behavior. As a result, producing a functional engineered biological system usually requires extensive manual tuning by trial-and-error, a timeconsuming process that significantly slows the biological design process. The lack of predictive power in current models is partly because these models account for only the synthetic circuits themselves, but not other ongoing processes in the cells in which they reside. However, the complex dynamics of synthetic circuits may affect the host cell and vice versa, leading to divergence between current models and experimental results. Recently, a whole-cell model of a small and simple bacteri...

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Section: Introductionmentioning

confidence: 99%

Towards a whole-cell modeling approach for synthetic biology

Purcell

Jain

Karr

et al. 2013

Chaos: An Interdisciplinary Journal of Nonlinear Science

Self Cite

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“…Powered by this emerging capability to program cells into living computers (1)(2)(3)(4)(5)(6), the integration of genetically encoded cells into freestanding materials and devices will not only provide new tools for scientific research but also, lead to unprecedented technological applications (7). However, the development of such living materials and devices has been significantly hampered by the demanding requirements for maintaining viable and functional cells in materials and devices plus biosafety concerns toward the release of genetically modified organisms into environments.…”

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confidence: 99%

Stretchable living materials and devices with hydrogel–elastomer hybrids hosting programmed cells

Liu

Tang

Tham

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Living systems, such as bacteria, yeasts, and mammalian cells, can be genetically programmed with synthetic circuits that execute sensing, computing, memory, and response functions. Integrating these functional living components into materials and devices will provide powerful tools for scientific research and enable new technological applications. However, it has been a grand challenge to maintain the viability, functionality, and safety of living components in freestanding materials and devices, which frequently undergo deformations during applications. Here, we report the design of a set of living materials and devices based on stretchable, robust, and biocompatible hydrogel-elastomer hybrids that host various types of genetically engineered bacterial cells. The hydrogel provides sustainable supplies of water and nutrients, and the elastomer is air-permeable, maintaining long-term viability and functionality of the encapsulated cells. Communication between different bacterial strains and with the environment is achieved via diffusion of molecules in the hydrogel. The high stretchability and robustness of the hydrogel-elastomer hybrids prevent leakage of cells from the living materials and devices, even under large deformations. We show functions and applications of stretchable living sensors that are responsive to multiple chemicals in a variety of form factors, including skin patches and gloves-based sensors. We further develop a quantitative model that couples transportation of signaling molecules and cellular response to aid the design of future living materials and devices. hydrogels | synthetic biology | genetically engineered bacteria | biochemical sensors | wearable devices G enetically engineered cells enabled by synthetic biology have accomplished multiple programmable functions, including sensing (1), responding (2), computing (3), and recording (4). Powered by this emerging capability to program cells into living computers (1-6), the integration of genetically encoded cells into freestanding materials and devices will not only provide new tools for scientific research but also, lead to unprecedented technological applications (7). However, the development of such living materials and devices has been significantly hampered by the demanding requirements for maintaining viable and functional cells in materials and devices plus biosafety concerns toward the release of genetically modified organisms into environments. For example, gene networks embedded in paper matrices have been used for low-cost rapid viruses detection and protein manufacturing (1). However, their gene networks are based on freeze-dried extracts from genetically engineered cells to operate, partially because the paper substrates cannot sustain long-term viability and functionality of living cells or prevent their leakage. As another example, by seeding cardiomyocytes on thin elastomer films, biohybrid devices have been developed as soft actuators (8) and biomimetic robots (9). However, because the cells are not protected or isolated...

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“…Inspired by both these natural circuits and physical computing devices, synthetic biologists are designing sophisticated synthetic circuits that can perform complicated "computing-like" behaviors. Synthetic biologists have designed gene circuits executing a wide range of functionalities including switches 4 , oscillators 5 , counters 6 , and even cell-to-cell communicators 7 .Despite these successes, many challenges to harnessing the full potential of synthetic biology persist [8][9][10][11][12][13][14][15] . While there are guiding principles to synthetic biology 16 , actual construction of synthetic circuits often proceeds in an ad-hoc manner through a mixture of biological intuition and trial-and-error.…”

mentioning

confidence: 99%

“…Despite these successes, many challenges to harnessing the full potential of synthetic biology persist [8][9][10][11][12][13][14][15] . While there are guiding principles to synthetic biology 16 , actual construction of synthetic circuits often proceeds in an ad-hoc manner through a mixture of biological intuition and trial-and-error.…”

mentioning

confidence: 99%

Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

2016

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A central goal of synthetic biology is to design sophisticated synthetic cellular circuits that can perform complex computations and information processing tasks in response to specific inputs. The tremendous advances in our ability to understand and manipulate cellular information processing networks raises several fundamental physics questions: How do the molecular components of cellular circuits exploit energy consumption to improve information processing? Can one utilize ideas from thermodynamics to improve the design of synthetic cellular circuits and modules? Here, we summarize recent theoretical work addressing these questions. Energy consumption in cellular circuits serves five basic purposes: (1) increasing specificity, (2) manipulating dynamics, (3) reducing variability, (4) amplifying signal, and (5) erasing memory. We demonstrate these ideas using several simple examples and discuss the implications of these theoretical ideas for the emerging field of synthetic biology. We conclude by discussing how it may be possible to overcome these limitations using "post-translational" synthetic biology that exploits reversible protein modification.Cells live in complex and dynamic environments. They sense and respond to both external environmental cues and to each other through cell-to-cell communication.Adapting to changing environments often requires cells to perform complex information processing, and cells have developed elaborate signaling networks to accomplish this feat. These biochemical networks are ubiquitous in biology, ranging from the quorum-sensing 1 and chemotaxis networks 2 in single-celled organisms to developmental networks in higher organisms 3 . Inspired by both these natural circuits and physical computing devices, synthetic biologists are designing sophisticated synthetic circuits that can perform complicated "computing-like" behaviors. Synthetic biologists have designed gene circuits executing a wide range of functionalities including switches 4 , oscillators 5 , counters 6 , and even cell-to-cell communicators 7 .Despite these successes, many challenges to harnessing the full potential of synthetic biology persist [8][9][10][11][12][13][14][15] . While there are guiding principles to synthetic biology 16 , actual construction of synthetic circuits often proceeds in an ad-hoc manner through a mixture of biological intuition and trial-and-error. Furthermore, the functionality and applicability is limited by a dearth of biological components 17 . For this reason, it would be helpful to identify general principles that can improve the design of synthetic circuits and help guide the search for new biological parts. One promising direction along these lines is recent work examining the relationship between the information processing capabilities of these biochemical networks and their energetic costs (technically this is usually a cost in free energy, but for the sake of brevity we will refer to this as energy). Energetic costs place important constraints on the design of physical computing de...

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Synthetic Biology: An Emerging Engineering Discipline

Cited by 211 publications

References 134 publications

Towards a whole-cell modeling approach for synthetic biology

Towards a whole-cell modeling approach for synthetic biology

Stretchable living materials and devices with hydrogel–elastomer hybrids hosting programmed cells

Landauer in the Age of Synthetic Biology: Energy Consumption and Information Processing in Biochemical Networks

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