All articles tagged with syntheticbiology from citeulike are automatically listed here.
| bibtexCitation | bibtexEntryType | abstract | author | citeulike-article-id | doi | journal | keywords | month | number | pages | posted-at | priority | title | url | volume | year | address | issn | publisher |
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| citeulike:142488 | article | Accurately predicting noise propagation in gene networks is crucial for understanding signal fidelity in natural networks and designing noise-tolerant gene circuits. To quantify how noise propagates through gene networks, we measured expression correlations between genes in single cells. We found that noise in a gene was determined by its intrinsic fluctuations, transmitted noise from upstream genes, and global noise affecting all genes. A model was developed that explains the complex behavior exhibited by the correlations and reveals the dominant noise sources. The model successfully predicts the correlations as the network is systematically perturbed. This approach provides a step toward understanding and manipulating noise propagation in more complex gene networks. | Pedraza, Juan M. ; van Oudenaarden, Alexander | 142488 | 10.1126/science.1109090 | Science | avano\_lab, expression, gene, genecircuits, geneticnetworks, genevariation, networks, noise, stochastic, syntheticbiology | March | 5717 | 1965--1969 | 2006-08-11 09:49:05 | 2 | Noise Propagation in Gene Networks | http://dx.doi.org/10.1126/science.1109090 | 307 | 2005 | |||
| citeulike:524531 | article | Bacteria can sense their environment, distinguish between cell types, and deliver proteins to eukaryotic cells. Here, we engineer the interaction between bacteria and cancer cells to depend on heterologous environmental signals. We have characterized invasin from Yersinia pseudotuburculosis as an output module that enables Escherichia coli to invade cancer-derived cells, including HeLa, HepG2, and U2OS lines. To environmentally restrict invasion, we placed this module under the control of heterologous sensors. With the Vibrio fischeri lux quorum sensing circuit, the hypoxia-responsive fdhF promoter, or the arabinose-inducible araBAD promoter, the bacteria invade cells at densities greater than 10(8)bacteria/ml, after growth in an anaerobic growth chamber or in the presence of 0.02\% arabinose, respectively. In the process, we developed a technique to tune the linkage between a sensor and output gene using ribosome binding site libraries and genetic selection. This approach could be used to engineer bacteria to sense the microenvironment of a tumor and respond by invading cancerous cells and releasing a cytotoxic agent. | Anderson, J. C. ; Clarke, E. J. ; Arkin, A. P. ; Voigt, C. A. | 524531 | 10.1016/j.jmb.2005.10.076 | J Mol Biol | ecoli, syntheticbiology | January | 4 | 619--627 | 2006-03-01 03:29:19 | 4 | Environmentally controlled invasion of cancer cells by engineered bacteria. | http://dx.doi.org/10.1016/j.jmb.2005.10.076 | 355 | 2006 | Howard Hughes Medical Institute, California Institute of Quantitative Biology Department of Bioengineering, University of California, 717 Potter Street, Room 257 Berkeley, CA 94720, USA. | 0022-2836 | |
| citeulike:464453 | article | Mycoplasma genitalium has the smallest genome of any organism that can be grown in pure culture. It has a minimal metabolism and little genomic redundancy. Consequently, its genome is expected to be a close approximation to the minimal set of genes needed to sustain bacterial life. Using global transposon mutagenesis, we isolated and characterized gene disruption mutants for 100 different nonessential protein-coding genes. None of the 43 RNA-coding genes were disrupted. Herein, we identify 382 of the 482 M. genitalium protein-coding genes as essential, plus five sets of disrupted genes that encode proteins with potentially redundant essential functions, such as phosphate transport. Genes encoding proteins of unknown function constitute 28\% of the essential protein-coding genes set. Disruption of some genes accelerated M. genitalium growth. | Glass, John I. ; Assad-Garcia, Nacyra ; Alperovich, Nina ; Yooseph, Shibu ; Lewis, Matthew R. ; Maruf, Mahir ; Hutchison, Clyde A. ; Smith, Hamilton O. ; Venter, Craig J. | 464453 | 10.1073/pnas.0510013103 | PNAS | minimalgenome, syntheticbiology | January | 2 | 425--430 | 2006-03-09 00:57:28 | 5 | Essential genes of a minimal bacterium | http://dx.doi.org/10.1073/pnas.0510013103 | 103 | 2006 | |||
| citeulike:521084 | article | Parikh, Monal R. ; Greene, Dina N. ; Woods, Kristen K. ; Matsumura, Ichiro | 521084 | 10.1093/protein/gzj010 | Protein Engineering, Design and Selection | biology, ecoli, energy, synthetic, syntheticbiology | March | 3 | 113--119 | 2006-06-05 20:42:48 | 4 | Directed evolution of RuBisCO hypermorphs through genetic selection in engineered E.coli | http://dx.doi.org/10.1093/protein/gzj010 | 19 | 2006 | 1741-0126 | Oxford University Press | ||
| citeulike:682586 | article | Misawa, N. ; Satomi, Y. ; Kondo, K. ; Yokoyama, A. ; Kajiwara, S. ; Saito, T. ; Ohtani, T. ; Miki, W. | 682586 | J. Bacteriol. | ecoli, energy, syntheticbiology | November | 22 | 6575--6584 | 2006-06-03 07:46:14 | 4 | Structure and functional analysis of a marine bacterial carotenoid biosynthesis gene cluster and astaxanthin biosynthetic pathway proposed at the gene level | http://jb.asm.org/cgi/content/abstract/177/22/6575 | 177 | 1995 | |||||
| citeulike:2837 | article | Shaner, Nathan C. ; Campbell, Robert E. ; Steinbach, Paul A. ; Giepmans, Ben N. G. ; Palmer, Amy E. ; Tsien, Roger Y. | 2837 | 10.1038/nbt1037 | Nature Biotechnology | fluorescentreporter, syntheticbiology | November | 12 | 1567+ | 2006-05-29 22:46:09 | 0 | Improved monomeric red, orange and yellow fluorescent proteins derived from Discosoma sp. red fluorescent protein | http://dx.doi.org/10.1038/nbt1037 | 22 | 2004 | ||||
| citeulike:306413 | article | Gene function is typically evaluated by sampling the continuum of gene expression at only a few discrete points corresponding to gene knockout or overexpression. We argue that this characterization is incomplete and present a library of engineered promoters of varying strengths obtained through mutagenesis of a constitutive promoter. A multifaceted characterization of the library, especially at the single-cell level to ensure homogeneity, permitted quantitative assessment correlating the effect of gene expression levels to improved growth and product formation phenotypes in Escherichia coli. Integration of these promoters into the chromosome can allow for a quantitative accurate assessment of genetic control. To this end, we used the characterized library of promoters to assess the impact of phosphoenolpyruvate carboxylase levels on growth yield and deoxy-xylulose-P synthase levels on lycopene production. The multifaceted characterization of promoter strength enabled identification of optimal expression levels for ppc and dxs, which maximized the desired phenotype. Additionally, in a strain preengineered to produce lycopene, the response to deoxy-xylulose-P synthase levels was linear at all levels tested, indicative of a rate-limiting step, unlike the parental strain, which exhibited an optimum expression level, illustrating that optimal gene expression levels are variable and dependent on the genetic background of the strain. This promoter library concept is illustrated as being generalizable to eukaryotic organisms (Saccharomyces cerevisiae) and thus constitutes an integral platform for functional genomics, synthetic biology, and metabolic engineering endeavors. | Alper, Hal ; Fischer, Curt ; Nevoigt, Elke ; Stephanopoulos, Gregory | 306413 | 10.1073/pnas.0504604102 | Proc Natl Acad Sci U S A | syntheticbiology | August | 2006-05-19 19:56:31 | 2 | Tuning genetic control through promoter engineering. | http://dx.doi.org/10.1073/pnas.0504604102 | 2005 | Department of Chemical Engineering, Massachusetts Institute of Technology, Room 56-469, Cambridge, MA 02139. | 0027-8424 | ||||
| citeulike:687437 | article | Allosteric nucleic acid ligases have been used previously to transform analyte-binding into the formation of oligonucleotide templates that can be amplified and detected. We have engineered binary deoxyribozyme ligases whose two components are brought together by bridging oligonucleotide effectors. The engineered ligases can 'read' one sequence and then 'write' (by ligation) a separate, distinct sequence, which can in turn be uniquely amplified. The binary deoxyribozymes show great specificity, can discriminate against a small number of mutations in the effector, and can read and recode DNA information with high fidelity even in the presence of excess obscuring genomic DNA. In addition, the binary deoxyribozymes can read non-natural nucleotides and write natural sequence information. The binary deoxyribozyme ligases could potentially be used in a variety of applications, including the detection of single nucleotide polymorphisms in genomic DNA or the identification of short nucleic acids such as microRNAs. | Tabor, J. J. ; Levy, M. ; Ellington, A. D. | 687437 | 10.1093/nar/gkl176 | Nucleic Acids Res | ecoli, rna, syntheticbiology | 8 | 2166--2172 | 2006-06-06 20:40:53 | 4 | Deoxyribozymes that recode sequence information. | http://dx.doi.org/10.1093/nar/gkl176 | 34 | 2006 | Center for Systems and Synthetic Biology and Institute for Cell and Molecular Biology, University of Texas at Austin, Austin, TX 78712, USA. | 1362-4962 | ||
| citeulike:141524 | article | The quantitative relation between transcription factor concentrations and the rate of protein production from downstream genes is central to the function of genetic networks. Here we show that this relation, which we call the gene regulation function (GRF), fluctuates dynamically in individual living cells, thereby limiting the accuracy with which transcriptional genetic circuits can transfer signals. Using fluorescent reporter genes and fusion proteins, we characterized the bacteriophage lambda promoter P(R) in Escherichia coli. A novel technique based on binomial errors in protein partitioning enabled calibration of in vivo biochemical parameters in molecular units. We found that protein production rates fluctuate over a time scale of about one cell cycle, while intrinsic noise decays rapidly. Thus, biochemical parameters, noise, and slowly varying cellular states together determine the effective single-cell GRF. These results can form a basis for quantitative modeling of natural gene circuits and for design of synthetic ones. | Rosenfeld, N. ; Young, J. W. ; Alon, U. ; Swain, P. S. ; Elowitz, M. B. | 141524 | 10.1126/science.1106914 | Science | syntheticbiology | March | 5717 | 1962--1965 | 2006-03-21 01:42:22 | 4 | Gene regulation at the single-cell level. | http://dx.doi.org/10.1126/science.1106914 | 307 | 2005 | Departments of Molecular Cell Biology and Physics of Complex Systems, Weizmann Institute of Science, Rehovot, 76100, Israel. | 1095-9203 | |
| citeulike:211037 | article | Church, George M. | 211037 | 10.1038/msb4100007 | Molecular Systems Biology | syntheticbiology, systemsbiology, thoughtleaders | March | 1 | msb4100007-E1--msb4100007-E2 | 2007-08-03 06:08:57 | 0 | From systems biology to synthetic biology | http://dx.doi.org/10.1038/msb4100007 | 1 | 2005 | Nature Publishing Group | |||
| citeulike:1526398 | article | Wong, Wilson W. ; Tsai, Tony Y. ; Liao, James C. | 1526398 | 10.1038/msb4100172 | Mol Syst Biol | degradation, ssra, syntheticbiology, tag | July | 2007-08-27 01:52:34 | 0 | Single-cell zeroth-order protein degradation enhances the robustness of synthetic oscillator | http://dx.doi.org/10.1038/msb4100172 | 3 | 2007 | ||||||
| citeulike:1595400 | article | Anderson, Christopher J. ; Voigt, Christopher A. ; Arkin, Adam P. | 1595400 | 10.1038/msb4100173 | Mol Syst Biol | gates, logic, modularity, syntheticbiology | 2007-08-27 01:50:06 | 0 | Environmental signal integration by a modular AND gate | http://dx.doi.org/10.1038/msb4100173 | 3 | 2007 | |||||||
| citeulike:1916535 | article | Rosenfeld, Nitzan ; Young, Jonathan W. ; Alon, Uri ; Swain, Peter S. ; Elowitz, Michael B. | 1916535 | 10.1038/msb4100185 | Mol Syst Biol | circuit, prediction, syntheticbiology | November | 2007-12-30 03:35:39 | 0 | Accurate prediction of gene feedback circuit behavior from component properties | http://dx.doi.org/10.1038/msb4100185 | 3 | 2007 | EMBO and Nature Publishing Group | |||||
| citeulike:2213003 | article | In the field of synthetic biology, recent genetic engineering efforts have enabled the construction of novel genetic circuits with diverse functionalities and unique activation mechanisms. Because of these advances, artificial genetic networks are becoming increasingly complex, and are demonstrating more robust behaviors with reduced crosstalk between defined modules. These properties have allowed for the identification of a growing set of design principles that govern genetic networks, and led to an increased number of applications for genetic circuits in the fields of metabolic engineering and biomedical engineering. Such progress indicates that synthetic biology is rapidly evolving into an integrated engineering practice that uses rational and combinatorial design of synthetic gene networks to solve complex problems in biology, medicine, and human health. | Sayut, D. J. ; Kambam, P. K. ; Sun, L. | 2213003 | 10.1039/b700547d | Mol Biosyst | syntheticbiology | December | 12 | 835--840 | 2008-01-10 04:22:33 | 2 | Engineering and applications of genetic circuits. | http://dx.doi.org/10.1039/b700547d | 3 | 2007 | Department of Chemical Engineering, University of Massachusetts Amherst, 686 N. Pleasant Street, Amherst, MA 01003. lsun@ecs.umass.edu. | 1742-206X | |
| citeulike:2169082 | article | Synthetic biology has a promising outlook in biotechnology and for understanding the self-organizing principle of biological molecules in life. However, synthetic biologists have been looking for new molecular "parts" that function as modular units required in designing and constructing new "devices" and "systems" for regulating cell function because the number of such parts is strictly limited at present. In this review, we focus on RNA/ribonucleoprotein (RNP) architectures that hold promise as new "parts" for synthetic biology. They are constructed with molecular design and an experimental evolution technique. So far, designed self-folding RNAs, RNA (RNP) enzymes, and nanoscale RNA architectures have been successfully constructed by utilizing Watson-Crick base-pairs together with specific RNA-RNA or RNA-protein binding motifs of known defined 3D structures. Riboregulators for regulating targeted gene expression have also been designed and produced in vitro as well as in vivo. Lately, RNA and ribonucleoprotein complexes have been strongly attracting the attention of molecular biologists because a variety of noncoding RNAs discovered in nature perform spatiotemporal gene expressions. Thus we hope that newly accumulating knowledge on naturally occurring RNAs and RNP complexes will provide a variety of new parts, devices and systems for synthetic biology. | Saito, Hirohide ; Inoue, Tan | 2169082 | 10.1016/j.jbiotec.2007.07.952 | Journal of Biotechnology | design, ribozyme, rna, syntheticbiology | October | 1 | 1--7 | 2007-12-26 03:48:47 | 0 | RNA and RNP as new molecular parts in synthetic biology | http://dx.doi.org/10.1016/j.jbiotec.2007.07.952 | 132 | 2007 | |||
| citeulike:2587778 | article | Plasmid-borne gene expression systems have found wide application in the emerging fields of systems biology and synthetic biology, where plasmids are used to implement simple network architectures, either to test systems biology hypotheses about issues such as gene expression noise or as a means of exerting artificial control over a cell's dynamics. In both these cases, fluorescent proteins are commonly applied as a means of monitoring the expression of genes in the living cell, and efforts have been made to quantify protein expression levels through fluorescence intensity calibration and by monitoring the partitioning of proteins among the two daughter cells after division; such quantification is important in formulating the predictive models desired in systems and synthetic biology research. A potential pitfall of using plasmid-based gene expression systems is that the high protein levels associated with expression from plasmids can lead to the formation of inclusion bodies, insoluble aggregates of misfolded, nonfunctional proteins that will not generate fluorescence output; proteins caught in these inclusion bodies are thus "dark" to fluorescence-based detection methods. If significant numbers of proteins are incorporated into inclusion bodies rather than becoming biologically active, quantitative results obtained by fluorescent measurements will be skewed; we investigate this phenomenon here. We have created two plasmid constructs with differing average copy numbers, both incorporating an unregulated promoter (P(LtetO-1) in the absence of TetR) expressing the GFP derivative enhanced green fluorescent protein (EGFP), and inserted them into Escherichia coli bacterial cells (a common model organism for work on the dynamics of prokaryotic gene expression). We extracted the inclusion bodies, denatured them, and refolded them to render them active, obtaining a measurement of the average number of EGFP per cell locked into these aggregates; at the same time, we used calibrated fluorescent intensity measurements to determine the average number of active EGFP present per cell. Both measurements were carried out as a function of cellular doubling time, over a range of 45-75 min. We found that the ratio of inclusion body EGFP to active EGFP varied strongly as a function of the cellular growth rate, and that the number of "dark" proteins in the aggregates could in fact be substantial, reaching ratios as high as approximately five proteins locked into inclusion bodies for every active protein (at the fastest growth rate), and dropping to ratios well below 1 (for the slowest growth rate). Our results suggest that efforts to compare computational models to protein numbers derived from fluorescence measurements should take inclusion body loss into account, especially when working with rapidly growing cells. Proteins 2008. (c) 2008 Wiley-Liss, Inc. | Iafolla, Marco A J A. ; Mazumder, Mostafizur ; Sardana, Vandit ; Velauthapillai, Tharsan ; Pannu, Karanbir ; McMillen, David R R. | 2587778 | 10.1002/prot.22024 | Proteins | body, gfp, inclusion, syntheticbiology, useful | March | 2008-03-25 22:38:26 | 0 | Dark proteins: Effect of inclusion body formation on quantification of protein expression. | http://dx.doi.org/10.1002/prot.22024 | 2008 | Department of Chemical and Physical Sciences, and Institute for Optical Sciences, University of Toronto Mississauga, Mississauga ON L5L 1C6, Canada. | 1097-0134 | ||||
| citeulike:2162716 | article | Yeh, Brian J. ; Lim, Wendell A. | 2162716 | 10.1038/nchembio0907-521 | Nat Chem Biol | commentary, syntheticbiology | 9 | 521--525 | 2007-12-23 23:31:04 | 0 | Synthetic biology: lessons from the history of synthetic organic chemistry | http://dx.doi.org/10.1038/nchembio0907-521 | 3 | 2007 | |||||
| citeulike:2230829 | article | Engineered microbes are of great potential utility in biotechnology and basic research. In principle, a cell can be built from scratch by assembling small molecule sets with auto-catalytic properties. Alternatively, DNA can be isolated or directly synthesized and molded into a synthetic genome using existing genomic blueprints and molecular biology tools. Activating such a synthetic genome will yield a synthetic cell. Here we examine obstacles associated with this latter approach using a model system whereby a donor genome from H. influenzae is fragmented, and the pieces are then modified and reassembled stepwise in an E. coli host cell. There are obstacles associated with this strategy related to DNA transfer, DNA replication, cross-talk in gene regulation and compatibility of gene products between donor and host. Encouragingly, analysis of gene expression indicates widespread transcription of H. influenzae genes in E. coli, and analysis of gap locations in H. influenzae and other microbial genome assemblies reveals few genes routinely incompatible with E. coli. In conclusion, rebuilding and booting a genome remains a feasible and pragmatic approach to creating a synthetic microbial cell. BioEssays 29:580-590, 2007. {\copyright} 2007 Wiley Periodicals, Inc. | Holt, Robert A. ; Warren, Rene ; Flibotte, Stephane ; Missirlis, Perseus I. ; Smailus, Duane E. | 2230829 | 10.1002/bies.20585 | BioEssays | genome, syntheticbiology, transfer | 6 | 580--590 | 2008-01-14 15:29:13 | 0 | Rebuilding microbial genomes | http://dx.doi.org/10.1002/bies.20585 | 29 | 2007 | Canada's Michael Smith Genome Sciences Centre, Vancouver, British Columbia, Canada | |||
| citeulike:2169164 | article | Motivation: The sequence of artificial genetic constructs is composed of multiple functional fragments, or genetic parts, involved in different molecular steps of gene expression mechanisms. Biologists have deciphered structural rules that the design of genetic constructs needs to follow in order to ensure a successful completion of the gene expression process, but these rules have not been formalized, making it challenging for non-specialists to benefit from the recent progress in gene synthesis. Results: We show that context-free grammars (CFG) can formalize these design principles. This approach provides a path to organizing libraries of genetic parts according to their biological functions, which correspond to the syntactic categories of the CFG. It also provides a framework for the systematic design of new genetic constructs consistent with the design principles expressed in the CFG. Using parsing algorithms, this syntactic model enables the verification of existing constructs. We illustrate these possibilities by describing a CFG that generates the most common architectures of genetic constructs in Escherichia coli. Availability: A web site allows readers to experiment with the algorithms presented in this article: www.genocad.org Contact: peccoud@vt.edu Supplementary information: Sequences and models are available at Bioinformatics online. 10.1093/bioinformatics/btm446 | Cai, Yizhi ; Hartnett, Brian ; Gustafsson, Claes ; Peccoud, Jean | 2169164 | 10.1093/bioinformatics/btm446 | Bioinformatics | abstraction, grammar, parts, syntheticbiology | October | 20 | 2760--2767 | 2007-12-26 04:23:47 | 0 | A syntactic model to design and verify synthetic genetic constructs derived from standard biological parts | http://dx.doi.org/10.1093/bioinformatics/btm446 | 23 | 2007 | |||
| citeulike:1003874 | article | Kim, Jongmin ; White, Kristin S. ; Winfree, Erik | 1003874 | 10.1038/msb4100099 | Mol Syst Biol | circuit, dna, invitro, rna, syntheticbiology, transcription | December | 2008-03-17 19:30:17 | 0 | Construction of an in vitro bistable circuit from synthetic transcriptional switches | http://dx.doi.org/10.1038/msb4100099 | 2 | 2006 | ||||||
| citeulike:1073636 | article | Genetic engineering is entering a new era, where microorganisms can be programmed using synthetic constructs of DNA encoding logic and operational commands. A toolbox of modular genetic parts is being developed, comprised of cell-based environmental sensors and genetic circuits. Systems have already been designed to be interconnected with each other and interfaced with the control of cellular processes. Engineering theory will provide a predictive framework to design operational multicomponent systems. On the basis of these developments, increasingly complex cellular machines are being constructed to build specialty chemicals, weave biomaterials, and to deliver therapeutics. | Voigt, C. A. | 1073636 | 10.1016/j.copbio.2006.09.001 | Curr Opin Biotechnol | syntheticbiology | October | 5 | 548--557 | 2007-09-11 22:46:00 | 0 | Genetic parts to program bacteria. | http://dx.doi.org/10.1016/j.copbio.2006.09.001 | 17 | 2006 | Biophysics and Chemistry \& Chemical Biology, Department of Pharmaceutical Chemistry, University of California San Francisco, QB3 Box 2540, 1700 4th Street, San Francisco, CA 94158, USA. cavoigt@picasso.ucsf.edu | 0958-1669 | |
| citeulike:2481328 | article | Bacteria employ quorum sensing, a form of cell-cell communication, to sense changes in the population density and regulate gene expression accordingly. This work investigates rewiring of one quorum-sensing module, the lux circuit from the marine bacterium Vibrio fischeri. Steady-state experiments demonstrate that rewiring the network architecture of this module can yield graded, threshold, and bi-stable gene expression as predicted by a mathematical model. The experiments also show that the native lux operon is most consistent with a threshold as opposed to bi-stable response. Each of the rewired networks yielded functional population sensors at biologically relevant conditions, suggesting that this operon is particu-larly robust. These findings (1) permit prediction of the behaviors of quorum-sensing operons in bacterial pathogens and (2) facilitate forward engineering of synthetic gene circuits. 10.1128/AEM.01688-07 | Haseltine, Eric L. ; Arnold, Frances H. | 2481328 | 10.1128/AEM.01688-07 | Appl. Environ. Microbiol. | syntheticbiology | November | AEM.01688-07+ | 2008-03-07 02:10:59 | 2 | Implications of Rewiring Bacterial Quorum Sensing | http://dx.doi.org/10.1128/AEM.01688-07 | 2007 | |||||
| citeulike:2413970 | article | Del Vecchio, Domitilla ; Ninfa, Alexander J. ; Sontag, Eduardo D. | 2413970 | 10.1038/msb4100204 | Mol Syst Biol | excellent, modularity, syntheticbiology | February | 2008-03-24 17:37:50 | 0 | Modular cell biology: retroactivity and insulation | http://dx.doi.org/10.1038/msb4100204 | 4 | 2008 | EMBO and Nature Publishing Group | |||||
| citeulike:1866782 | article | The ability to logically engineer novel cellular functions promises a deeper understanding of biological systems. Here we demonstrate the rational design of cellular memory in yeast that employs autoregulatory transcriptional positive feedback. We built a set of transcriptional activators and quantitatively characterized their effects on gene expression in living cells. Modeling in conjunction with the quantitative characterization of the activator-promoter pairs accurately predicts the behavior of the memory network. This study demonstrates the power of taking advantage of components with measured quantitative parameters to specify eukaryotic regulatory networks with desired properties. | Ajo-Franklin, C. M. ; Drubin, D. A. ; Eskin, J. A. ; Gee, E. P. ; Landgraf, D. ; Phillips, I. ; Silver, P. A. | 1866782 | 10.1101/gad.1586107 | Genes Dev | logic, memory, syntheticbiology | September | 18 | 2271--2276 | 2007-12-26 03:37:28 | 0 | Rational design of memory in eukaryotic cells. | http://dx.doi.org/10.1101/gad.1586107 | 21 | 2007 | Department of Systems Biology, Harvard Medical School, Boston, MA 02115, USA. | 0890-9369 | |
| citeulike:1691183 | article | MOTIVATION: The goal of synthetic biology is to design and construct biological systems that present a desired behavior. The construction of synthetic gene networks implementing simple functions has demonstrated the feasibility of this approach. However, the design of these networks is difficult, notably because existing techniques and tools are not adapted to deal with uncertainties on molecular concentrations and parameter values. RESULTS: We propose an approach for the analysis of a class of uncertain piecewise-multiaffine differential equation models. This modeling framework is well adapted to the experimental data currently available. Moreover, these models present interesting mathematical properties that allow the development of efficient algorithms for solving robustness analyses and tuning problems. These algorithms are implemented in the tool RoVerGeNe, and their practical applicability and biological relevance are demonstrated on the analysis of the tuning of a synthetic transcriptional cascade built in Escherichia coli. AVAILABILITY: RoVerGeNe and the transcriptional cascade model are available at http://iasi.bu.edu/\%7Ebatt/rovergene/rovergene.htm. | Batt, G. ; Yordanov, B. ; Weiss, R. ; Belta, C. | 1691183 | 10.1093/bioinformatics/btm362 | Bioinformatics | modeling, syntheticbiology | September | 18 | 2415--2422 | 2007-12-26 03:36:09 | 0 | Robustness analysis and tuning of synthetic gene networks. | http://dx.doi.org/10.1093/bioinformatics/btm362 | 23 | 2007 | Centers for Information and Systems Engineering and for BioDynamics, Boston University, Boston, MA, USA. gregory.batt@imag.fr | 1460-2059 | |
| citeulike:1910555 | article | Cox, Robert S. ; Surette, Michael G. ; Elowitz, Michael B. | 1910555 | 10.1038/msb4100187 | Mol Syst Biol | design, excellent, promoter, rules, syntheticbiology | November | 2007-12-30 03:05:27 | 0 | Programming gene expression with combinatorial promoters | http://dx.doi.org/10.1038/msb4100187 | 3 | 2007 | EMBO and Nature Publishing Group | |||||
| citeulike:1595409 | article | Henkel, Joachim ; Maurer, Stephen M. | 1595409 | 10.1038/msb4100161 | Mol Syst Biol | syntheticbiology | June | 2007-08-27 02:00:43 | 0 | The economics of synthetic biology | http://dx.doi.org/10.1038/msb4100161 | 3 | 2007 | ||||||
| citeulike:2173789 | article | Summary Here we report the ribosomal polymerization of [alpha]-hydroxy acids by means of genetic code reprogramming. The flexizyme system, a ribozyme-based tRNA acylation tool, was used to reassign individual codons to seven types of [alpha]-hydroxy acids, and then polyesters were synthesized under controls of the reprogrammed genetic code using a reconstituted cell-free translation system. The sequence and length of the polyester segments were specified by the mRNA template, indicating that high-fidelity ribosome expression of polyesters was possible. This work opens a door for the mRNA-directed synthesis of backbone-altered biopolymers. | Ohta, Atsushi ; Murakami, Hiroshi ; Higashimura, Eri ; Suga, Hiroaki | 2173789 | 10.1016/j.chembiol.2007.10.015 | Chemistry \& Biology | code, genetic, invitro, neat, syntheticbiology, translation | December | 12 | 1315--1322 | 2007-12-26 23:24:59 | 0 | Synthesis of Polyester by Means of Genetic Code Reprogramming | http://dx.doi.org/10.1016/j.chembiol.2007.10.015 | 14 | 2007 | |||
| citeulike:1846870 | article | Microbial consortia form when multiple species colocalize and communally generate a function that none is capable of alone. Consortia abound in nature, and their cooperative metabolic activities influence everything from biodiversity in the global food chain to human weight gain. Here, we present an engineered consortium in which the microbial members communicate with each other and exhibit a "consensus" gene expression response. Two colocalized populations of Escherichia coli converse bidirectionally by exchanging acyl-homoserine lactone signals. The consortium generates the gene-expression response if and only if both populations are present at sufficient cell densities. Because neither population can respond without the other's signal, this consensus function can be considered a logical AND gate in which the inputs are cell populations. The microbial consensus consortium operates in diverse growth modes, including in a biofilm, where it sustains its response for several days. | Brenner, Katie ; Karig, David K K. ; Weiss, Ron ; Arnold, Frances H H. | 1846870 | 10.1073/pnas.0704256104 | Proc Natl Acad Sci U S A | circuit, quorum, sensing, syntheticbiology | October | 2008-01-01 23:18:43 | 0 | Engineered bidirectional communication mediates a consensus in a microbial biofilm consortium. | http://dx.doi.org/10.1073/pnas.0704256104 | 2007 | Division of Chemistry and Chemical Engineering, California Institute of Technology, MC 210-41, Pasadena, CA 91125. | 0027-8424 | ||||
| citeulike:1716154 | article | Although adjustable transgene expression systems are considered essential for future therapeutic and biopharmaceutical manufacturing applications, the currently available transcription control modalities all require side-effect-prone inducers such as immunosupressants, hormones and antibiotics for fine-tuning. We have designed a novel mammalian transcription-control system, which is reversibly fine-tuned by non-toxic vitamin H (also referred to as biotin). Ligation of vitamin H, by engineered Escherichia coli biotin ligase (BirA), to a synthetic biotinylation signal fused to the tetracycline-dependent transactivator (tTA), enables heterodimerization of tTA to a streptavidin-linked transrepressor domain (KRAB), thereby abolishing tTA-mediated transactivation of specific target promoters. As heterodimerization of tTA to KRAB is ultimately conditional upon the presence of vitamin H, the system is vitamin H responsive. Transgenic Chinese hamster ovary cells, engineered for vitamin H-responsive gene expression, showed high-level, adjustable and reversible production of a human model glycoprotein in bench-scale culture systems, bioreactor-based biopharmaceutical manufacturing scenarios, and after implantation into mice. The vitamin H-responsive expression systems showed unique band pass filter-like regulation features characterized by high-level expression at low (02 nM biotin), maximum repression at intermediate (1001000 nM biotin), and high-level expression at increased (>100 000 nM biotin) biotin concentrations. Sequential ON-to-OFF-to-ON, ON-to-OFF and OFF-to-ON expression profiles with graded expression transitions can all be achieved by simply increasing the level of a single inducer molecule without exchanging the culture medium. These novel expression characteristics mediated by an FDA-licensed inducer may foster advances in therapeutic cell engineering and manufacturing of difficult-to-produce protein therapeutics. 10.1093/nar/gkm466 | Weber, Wilfried ; Bacchus, William ; Daoud-El ; Fussenegger, Martin | 1716154 | 10.1093/nar/gkm466 | Nucl. Acids Res. | syntheticbiology | September | 17 | e116+ | 2007-12-26 01:04:37 | 0 | Vitamin H-regulated transgene expression in mammalian cells | http://dx.doi.org/10.1093/nar/gkm466 | 35 | 2007 | |||
| citeulike:2505250 | article | Riboswitches, as previously reported, are natural RNA aptamers that regulate the expression of numerous bacterial metabolic genes in response to small molecule ligands. It has recently been shown that these RNA genetic elements are also present near the splice site junctions of plant and fungal introns, thus raising the possibility of their involvement in regulating mRNA splicing. Here it is shown for the first time that a riboswitch can be engineered to regulate pre-mRNA splicing in vitro. We show that insertion of a high-affinity theophylline binding aptamer into the 3' splice site (3' ss) region of a model pre-mRNA (AdML-Theo29AG) enables its splicing to be repressed by the addition theophylline. Our results indicate that the location of 3' ss AG within the aptamer plays a crucial role in conferring theophylline-dependent control of pre-mRNA splicing. We also show that theophylline-mediated control of pre-mRNA splicing is highly specific by first demonstrating that a small molecule ligand similar in shape and size to theophylline had no effect on the splicing of AdML-Theo29AG pre-mRNA. Second, theophylline failed to exert any influence on the splicing of a pre-mRNA that does not contain its binding site. Third, theophylline specifically blocks the step II of the splicing reaction. Finally, we provide evidence that theophylline-dependent control of pre-mRNA splicing is functionally relevant. 10.1261/rna.2162205 | Kim, Dong-Suk ; Gusti, Veronica ; Pillai, Sailesh G. ; Gaur, Rajesh K. | 2505250 | 10.1261/rna.2162205 | RNA | riboswitch, splicing, syntheticbiology, theophylline | November | 11 | 1667--1677 | 2008-03-11 01:46:16 | 0 | An artificial riboswitch for controlling pre-mRNA splicing | http://dx.doi.org/10.1261/rna.2162205 | 11 | 2005 | |||
| citeulike:1591514 | article | Edited by Arthur D. Riggs, Beckman Research Institute, City of Hope, Duarte, CA, and approved July 12, 2007 (received for review May 1, 2007)Engineered biological systems hold promise in addressing pressing human needs in chemical processing, energy production, materials construction, and maintenance and enhancement of human health and the environment. However, significant advancements in our ability to engineer biological systems have been limited by the foundational tools available for reporting on, responding to, and controlling intracellular components in living systems. Portable and scalable platforms are needed for the reliable construction of such communication and control systems across diverse organisms. We report an extensible RNA-based framework for engineering ligand-controlled gene-regulatory systems, called ribozyme switches, that exhibits tunable regulation, design modularity, and target specificity. These switch platforms contain a sensor domain, comprised of an aptamer sequence, and an actuator domain, comprised of a hammerhead ribozyme sequence. We examined two modes of standardized information transmission between these domains and demonstrate a mechanism that allows for the reliable and modular assembly of functioning synthetic RNA switches and regulation of ribozyme activity in response to various effectors. In addition to demonstrating examples of small molecule-responsive, in vivo functional, allosteric hammerhead ribozymes, this work describes a general approach for the construction of portable and scalable gene-regulatory systems. We demonstrate the versatility of the platform in implementing application-specific control systems for small molecule-mediated regulation of cell growth and noninvasive in vivo sensing of metabolite production. 10.1073/pnas.0703961104 | Win, Maung N. ; Smolke, Christina D. | 1591514 | 10.1073/pnas.0703961104 | PNAS | ribozyme, syntheticbiology | August | 0703961104+ | 2007-10-16 21:37:33 | 0 | A modular and extensible RNA-based gene-regulatory platform for engineering cellular function | http://dx.doi.org/10.1073/pnas.0703961104 | 2007 |