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Abstract
A transistor is a device that amplifies and switches electronic signals. Bonnet et al. (p. 599, published online 28 March; see the Perspective by Benenson) engineered a genetic circuit to behave like a transistor in individual living cells. Instead of regulating messenger RNA levels, which has been used previously in designing such systems, the approach relied on changing the state of double-stranded DNA. Six basic logic gates were designed and constructed that were based on the activity of two serine recombinases. ...
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Abstract
Development, regeneration, and even day-to-day physiology require plant and animal cells to make decisions based on their locations. The principles by which cells may do this are deceptively straightforward. But when reliability needs to be high--as often occurs during development--successful strategies tend to be anything but simple. Increasingly, the challenge facing biologists is to relate the diverse diffusible molecules, control circuits, and gene regulatory networks ...
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Abstract
Genome-modification technologies enable the rational engineering and perturbation of biological systems. Historically, these methods have been limited to gene insertions or mutations at random or at a few pre-defined locations across the genome. The handful of methods capable of targetedgene editing suffered from low efficiencies, significant labor costs, or both. Recent advances have dramatically expanded our ability to engineer cells in a directed and combinatorial manner. Here, we review current technologies and methodologies for genome-scale engineering, discuss the prospects for extending ...
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Abstract
Microbial systems are being increasingly developed as production hosts for a wide variety of chemical compounds. Broader adoption of microbial synthesis is hampered by a limited number of high-yielding natural pathways for molecules with the desired physical properties, as well as the difficulty in functionally assembling complex biosynthetic pathways in heterologous hosts. Here, we address both of these challenges by reporting the adaptation of the butanol biosynthetic pathway for the synthesis of odd-chain molecules and the development of a complementary modular ...
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Abstract
Nature has evolved a treasury of biological molecules that are logically connected to networks, enabling cells to maintain their functional integrity. Similar to electronic circuits, cells operate as information-processing systems that dynamically integrate and respond to distinct input signals. Synthetic biology aims to standardize and expand the natural toolbox of biological building blocks to engineer novel synthetic networks in living systems. Mammalian cells harboring integrated ...
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Abstract
It has been proposed1 that gene-regulatory circuits with virtually any desired property can be constructed from networks of simple regulatory elements. These properties, which include multistability and oscillations, have been found in specialized gene circuits such as the bacteriophage switch2 and the Cyanobacteria circadian oscillator3. However, these behaviours have not been demonstrated in networks of non-specialized regulatory components. Here we present the construction of a genetic toggle switch—a synthetic, bistable gene-regulatory network—in Escherichia coli and provide a simple theory that ...
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Abstract
Synthetic genetic programs are built from circuits that integrate sensors and implement temporal control of gene expression. Transcriptional circuits are layered by using promoters to carry the signal between circuits. In other words, the output promoter of one circuit serves as the input promoter to the next. Thus, connecting circuits requires physically connecting a promoter to the next circuit. We show that the sequence at ...
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posted to syntheticbiology
by Yitapi
on 2012-11-23 08:18:53
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Abstract
Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits, and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is ...
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Abstract
BACKGROUND:Engineering genetic Boolean logic circuits is a major research theme of synthetic biology. By altering or introducing connections between genetic components, novel regulatory networks are built in order to mimic the behaviour of electronic devices such as logic gates. While electronics is a highly standardized science, genetic logic is still in its infancy, with few agreed standards. In this paper we focus on the interpretation of logical values in terms of molecular concentrations.RESULTS:We describe the results of computational investigations of a ...
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Abstract
Since it was launched in 2006, PLOS ONE has published over fifty articles illustrating the many facets of the emerging field of synthetic biology. This article reviews these publications by organizing them into broad categories focused on DNA synthesis and assembly techniques, the development of libraries of biological parts, the use of synthetic biology in protein engineering applications, and the engineering of gene regulatory networks ...
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Abstract
Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally ...
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posted to syntheticbiology
by TRHvidsten
on 2012-07-06 12:24:43
Abstract
Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical network structure. Chemical Reaction Network Theory (CRNT) may help at this level to decide whether a given network has the ...
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Abstract
Synthetic biology has advanced the design of standardized control devices that program cellular functions and metabolic activities in living organisms. Rational interconnection of these synthetic switches resulted in increasingly complex designer networks that execute input-triggered genetic instructions with precision, robustness and computational logic reminiscent of electronic circuits. Using trigger-controlled transcription factors, which independently control gene expression, and RNA-binding proteins that inhibit the translation of transcripts ...
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Abstract
A metabolism is a complex network of chemical reactions that converts sources of energy and chemical elements into biomass and other molecules. To design a metabolism from scratch and to implement it in a synthetic genome is almost within technological reach. Ideally, a synthetic metabolism should be able to synthesize a desired spectrum of molecules at a high rate, from multiple different nutrients, while using few chemical reactions, and producing little or no waste. Not all of these properties are achievable ...
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Abstract
Synthetic gene circuits are designed to program new biological behaviour, dynamics and logic control. For all but the simplest synthetic phenotypes, this requires a structured approach to map the desired functionality to available molecular and cellular parts and processes. In other engineering disciplines, a formalized design process has greatly enhanced the scope and rate of success of projects. When engineering biological systems, a desired function must be achieved in a context that is incompletely known, is influenced by stochastic fluctuations and ...
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by Vitor B. Pinheiro, Alexander I. Taylor, Christopher Cozens, et al.Mikhail Abramov, Marleen Renders, Su Zhang, John C. Chaput, Jesper Wengel, Sew-Yeu Peak-Chew, Stephen H. McLaughlin, Piet Herdewijn, Philipp Holliger
Abstract
Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We ...
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Abstract
Advances in synthetic biology are contributing to diverse research areas, from basic biology to biomanufacturing and disease therapy. We discuss the theoretical foundation, applications, and potential of this emerging field. ...
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Abstract
BACKGROUND:We consider the possibility of engineering metabolic pathways in a chassis organism in order to synthesize novel target compounds that are heterologous to the chassis. For this purpose, we model metabolic networks through hypergraphs where reactions are represented by hyperarcs. Each hyperarc represents an enzyme-catalyzed reaction that transforms set of substrates compounds into product compounds. We follow a retrosynthetic approach in order to search in the metabolic space (hypergraphs) for pathways (hyperpaths) linking the target compounds to a source set of ...
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Abstract
Synthetic biology aims to create functional devices, systems and organisms with novel and useful functions on the basis of catalogued and standardized biological building blocks. Although they were initially constructed to elucidate the dynamics of simple processes, designed devices now contribute to the understanding of disease mechanisms, provide novel diagnostic tools, enable economic production of therapeutics and allow the design of novel strategies for the treatment of cancer, immune diseases and metabolic disorders, such as diabetes and gout, as well as ...
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Abstract
The models and simulation tools available to design functionally complex synthetic biological devices are very limited. We formulated a design-driven approach that used mechanistic modeling and kinetic RNA folding simulations to engineer RNA-regulated genetic devices that control gene expression. Ribozyme and metabolite-controlled, aptazyme-regulated expression devices with quantitatively predictable functions were assembled from components characterized in vitro, in vivo, and in silico. The models and design ...
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Abstract
The field of Synthetic Biology seeks to apply engineering principles to biology in order to produce novel biological systems. One approach to accomplish this goal is the genome-driven cell engineering approach, which searches for functioning minimal genomes in naturally occurring microorganisms, which can then be used as a template for future systems. Currently a prototypical minimal genome has not been discovered. This review analyzes the ...
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Abstract
Here we introduce a new design framework for synthetic biology that exploits the advantages of Bayesian model selection. We will argue that the difference between inference and design is that in the former we try to reconstruct the system that has given rise to the data that we observe, whereas in the latter, we seek to construct the system that produces the data that we would like to observe, i.e., the desired behavior. Our approach allows us to exploit methods from ...
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Abstract
How synthetic can "synthetic biology" be? A literal interpretation of the name of this new life science discipline invokes expectations of the systematic construction of biological systems with cells being built module by module--from the bottom up. But can this possibly be achieved, taking into account the enormous complexity and redundancy of living systems, which distinguish them quite remarkably from design features that characterize human inventions? There are several recent developments in biology, in tight conjunction with quantitative disciplines, that may ...
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Abstract
A major goal of synthetic biology is to develop a deeper understanding of biological design principles from the bottom up, by building circuits and studying their behavior in cells. Investigators initially sought to design circuits “from scratch” that functioned as independently as possible from the underlying cellular system. More recently, researchers have begun to develop a new generation of synthetic circuits that integrate more closely with endogenous cellular processes. These approaches are providing fundamental insights into the regulatory architecture, dynamics, and ...
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Abstract
Caulobacter crescentus is a model organism for the integrated circuitry that runs a bacterial cell cycle. Full discovery of its essential genome, including non-coding, regulatory and coding elements, is a prerequisite for understanding the complete regulatory network of a bacterial cell. Using hyper-saturated transposon mutagenesis coupled with high-throughput sequencing, we determined the essential Caulobacter genome at 8 bp resolution, including 1012 essential genome features: 480 ORFs, 402 regulatory sequences and 130 non-coding elements, including 90 intergenic segments of unknown function. The ...
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Abstract
Synthetic biology is a recently emerging field that applies engineering formalisms to design and construct new biological parts, devices, and systems for novel functions or life forms that do not exist in nature. Synthetic biology relies on and shares tools from genetic engineering, bioengineering, systems biology and many other engineering disciplines. It is also different from these subjects, in both insights and approach. Applications of synthetic biology have great potential for novel contributions to established fields and for offering opportunities to ...
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In Current Opinion in Microbiology, Vol. 13, No. 2. (2010), 240-245
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
1369-5274
doi: DOI: 10.1016/j.mib.2010.01.003
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/msb.2008.24
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In The International Journal of Biochemistry & Cell Biology, Vol. In Press, Uncorrected Proof (2010)
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/nrg2697
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Abstract
The general central dogma frames the emergent properties of life, which make biology both necessary and difficult to engineer. In a process engineering paradigm, each biological process stream and process unit is heavily influenced by regulatory interactions and interactions with the surrounding environment. Synthetic biology is developing the tools and methods that will increase control over these interactions, eventually resulting in an integrative synthetic biology that will allow ground-up cellular optimization. In this review, we attempt to contextualize the areas of ...
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In Wiley Interdisciplinary Reviews: Systems Biology and Medicine, Vol. 3, No. 1. (2010), 7-20, doi:10.1002/wsbm.104
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Abstract
Synthetic biology has been used to describe many biological endeavors over the past thirty years-from designing enzymes and in vitro systems, to manipulating existing metabolisms and gene expression, to creating entirely synthetic replicating life forms. What separates the current incarnation of synthetic biology from the recombinant DNA technology or metabolic engineering of the past is an emphasis on principles from engineering such as modularity, standardization, and rigorously predictive models. As such, synthetic biology represents a new paradigm for learning about and ...
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by Anselm Levskaya, Aaron A. Chevalier, Jeffrey J. Tabor, et al.Zachary B. Simpson, Laura A. Lavery, Matthew Levy, Eric A. Davidson, Alexander Scouras, Andrew D. Ellington, Edward M. Marcotte, Christopher A. Voigt
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/nature04405
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/469171a
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/nchembio.378
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
Note (first note only)
10.1038/nrg2775
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In Trends in biotechnology, Vol. 28, No. 10. (2010), 534-542
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:06
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In Journal of Biological Engineering, Vol. 3, No. 1. (2009), 11
by Jordan Baumgardner, Karen Acker, Oyinade Adefuye, et al.Samuel Crowley, Will DeLoache, James Dickson, Lane Heard, Andrew Martens, Nickolaus Morton, Michelle Ritter, Amber Shoecraft, Jessica Treece, Matthew Unzicker, Amanda Valencia, Mike Waters, A. Malcolm Campbell, Laurie Heyer, Jeffrey Poet, Todd Eckdahl
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Abstract
BACKGROUND: The Hamiltonian Path Problem asks whether there is a route in a directed graph from a beginning node to an ending node, visiting each node exactly once. The Hamiltonian Path Problem is NP complete, achieving surprising computational complexity with modest increases in size. This challenge has inspired researchers to broaden the definition of a computer. DNA computers have been developed that solve NP complete problems. Bacterial computers can be programmed by constructing genetic circuits to execute an algorithm that is ...
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
10.1038/nature09565
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
10.1038/nchembio.369
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In Bioinformatics, Vol. 26, No. 20. (2010), 2633-2634
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Abstract
Motivation: RBSDesigner predicts the translation efficiency of existing mRNA sequences and designs synthetic ribosome binding sites (RBSs) for a given coding sequence (CDS) to yield a desired level of protein expression. The program implements the mathematical model for translation initiation described in Na et al. (Mathematical modeling of translation initiation for the estimation of its efficiency to computationally design mRNA sequences with a desired expression level in prokaryotes. BMC Syst. Biol., 4, 71). The program additionally incorporates the effect on translation ...
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by Dae-Kyun Ro, Eric M. Paradise, Mario Ouellet, et al.Karl J. Fisher, Karyn L. Newman, John M. Ndungu, Kimberly A. Ho, Rachel A. Eachus, Timothy S. Ham, James Kirby, Michelle C. Y. Chang, Sydnor T. Withers, Yoichiro Shiba, Richmond Sarpong, Jay D. Keasling
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
10.1038/nature04640
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
1552-4450
10.1038/nchembio719
10.1038/nchembio719
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In Current Opinion in Biotechnology, Vol. 19, No. 6. (2008), 556-563
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
doi: DOI: 10.1016/j.copbio.2008.10.014
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In Current Opinion in Biotechnology, Vol. 19, No. 5. (2008), 414-419
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
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In BMC Systems Biology, Vol. 4, No. 1. (2010), 71
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Abstract
BACKGROUND:Within the emerging field of synthetic biology, engineering paradigms have recently been used to design biological systems with novel functionalities. One of the essential challenges hampering the construction of such systems is the need to precisely optimize protein expression levels for robust operation. However, it is difficult to design mRNA sequences for expression at targeted protein levels, since even a few nucleotide modifications around the start codon may alter translational efficiency and dramatically (up to 250-fold) change protein expression. Previous studies ...
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In Cell, Vol. 144, No. 6. (2011), 855-859
posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
0092-8674
doi: DOI: 10.1016/j.cell.2011.02.020
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posted to syntheticbiology
by goksel
on 2011-06-26 22:27:05
Note (first note only)
10.1111/j.1365-2958.2008.06467.x
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