"Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology." http://bit.ly/100FQ9G
Encouraging the Advancement of Synthetic Biology at iGEM 2012 SelectScience.net (press release) April's edition of DECODED, the international IDT customer newsletter, features the pioneering synthetic biology work of the Slovenian team (runners up...
by Stephan Binder, Solvej Siedler, Jan Marienhagen, Michael Bott and Lothar Eggeling
"Recombineering in bacteria is a powerful technique for genome reconstruction, but until now, it was not generally applicable for development of small-molecule producers because of the inconspicuous phenotype of most compounds of biotechnological relevance. Here, we establish recombineering for Corynebacterium glutamicum using RecT of prophage Rac and combine this with our recently developed nanosensor technology, which enables the detection and isolation of productive mutants at the single-cell level via fluorescence-activated cell sorting (FACS). We call this new technology RecFACS, which we use for genomic site-directed saturation mutagenesis without relying on pre-constructed libraries to directly isolate L-lysine-producing cells. A mixture of 19 different oligonucleotides was used targeting codon 81 in murE of the wild-type, at a locus where one single mutation is known to cause L-lysine production. Using RecFACS, productive mutants were screened and isolated. Sequencing revealed 12 different amino acid exchanges in the targeted murE codon, which caused different L-lysine production titers. Apart from introducing a rapid genome construction technology for C. glutamicum, the present work demonstrates that RecFACS is suitable to simply create producers as well as genetic diversity in one single step, thus establishing a new general concept in synthetic biology."
Register now for the 12 Annual Genomics Symposium entitled "Synthetic Biology & Microbial Ecology". The symposium takes place on June 7th. Reserve your spot now!
"The emergence and future of mammalian synthetic biology depends on technologies for orchestrating and custom tailoring complementary gene expression and signaling processes in a predictable manner. Here, we demonstrate for the first time multi-chromatic expression control in mammalian cells by differentially inducing up to three genes in a single cell culture in response to light of different wavelengths. To this end, we developed an ultraviolet B (UVB)-inducible expression system by designing a UVB-responsive split transcription factor based on the Arabidopsis thaliana UVB receptor UVR8 and the WD40 domain of COP1. The system allowed high (up to 800-fold) UVB-induced gene expression in human, monkey, hamster and mouse cells. Based on a quantitative model, we determined critical system parameters. By combining this UVB-responsive system with blue and red light-inducible gene control technology, we demonstrate multi-chromatic multi-gene control by differentially expressing three genes in a single cell culture in mammalian cells, and we apply this system for the multi-chromatic control of angiogenic signaling processes. This portfolio of optogenetic tools enables the design and implementation of synthetic biological networks showing unmatched spatiotemporal precision for future research and biomedical applications."
"The engineering-based approach of synthetic biology is characterized by an assumption that ‘engineering by design’ enables the construction of ‘living machines’. These ‘machines’, as biological machines, are expected to display certain properties of life, such as adapting to changing environments and acting in a situated way. This paper proposes that a tension exists between the expectations placed on biological artefacts and the notion of producing such systems by means of engineering; this tension makes it seem implausible that biological systems, especially those with properties characteristic of living beings, can in fact be produced using the specific methods of engineering. We do not claim that engineering techniques have nothing to contribute to the biotechnological construction of biological artefacts. However, drawing on Descartes’s and Kant’s thinking on the relationship between the organism and the machine, we show that it is considerably more plausible to assume that distinctively biological artefacts emerge within a paradigm different from the paradigm of the Cartesian machine that underlies the engineering approach. We close by calling for increased attention to be paid to approaches within molecular biology and chemistry that rest on conceptions different from those of synthetic biology’s engineering paradigm." http://bit.ly/18loqVW
"Eric Topol joins us to discuss what was perhaps the most talked about book in the life sciences in 2012, The Creative Destruction of Medicine. In his book, Topol tells of the now arriving era of individualized medicine and the rise of "homo digitus," or digital man. In today's show, Topol dives into some key topics from the book such as how to deal with misaligned incentives in healthcare.
"I just wish I could go back and start medical school again because this is truly an era . . a renaissance, an enlightenment in the medical space," says Topol when asked about what he advises young people. Dr. Topol recently hosted the Future of Genomic Medicine Conference at The Scripps in San Diego, and he begins the interview giving some highlights of patient stories ..." Listen to the Podcast http://bit.ly/11SHdGh
"Engineered bacteria make self-assembling tetrahedra.
Practitioners of DNA origami have spent the better part of the past decade folding the molecule into minuscule smiley faces, boxes, letters of the alphabet and dozens of other intricate shapes. Proteins, on the other hand, have been rather late in joining the origami party — even though nature is adept at moulding them into a dazzling array of functional shapes, including molecular-recognition systems and catalysts. Now Roman Jerala, a biochemist at the National Institute of Chemistry in Ljubljana, Slovenia, is making up for lost time. He and his colleagues have designed and built a protein that folds itself into a tetrahedron — a pyramid with a triangular base — and he says that the strategy could be used to make a wide range of other shapes. Whereas examples of DNA origami often look pretty, few of these creations have any practical use. Proteins, on the other hand, are much better suited to performing useful tasks, such as delivering drugs, according to Jerala..."
*Design of a single-chain polypeptide tetrahedron assembled from coiled-coil segments* byHelena Gradišar, Sabina Božič, Tibor Doles, Damjan Vengust, Iva Hafner-Bratkovič, Alenka Mertelj, Ben Webb, Andrej Šali, Sandi Klavžar & Roman Jerala
"Protein structures evolved through a complex interplay of cooperative interactions, and it is still very challenging to design new protein folds de novo. Here we present a strategy to design self-assembling polypeptide nanostructured polyhedra based on modularization using orthogonal dimerizing segments. We designed and experimentally demonstrated the formation of the tetrahedron that self-assembles from a single polypeptide chain comprising 12 concatenated coiled coil–forming segments separated by flexible peptide hinges. The path of the polypeptide chain is guided by a defined order of segments that traverse each of the six edges of the tetrahedron exactly twice, forming coiled-coil dimers with their corresponding partners. The coincidence of the polypeptide termini in the same vertex is demonstrated by reconstituting a split fluorescent protein in the polypeptide with the correct tetrahedral topology. Polypeptides with a deleted or scrambled segment order fail to self-assemble correctly. This design platform provides a foundation for constructing new topological polypeptide folds based on the set of orthogonal interacting polypeptide segments." http://bit.ly/17tJn2A
and
*Self-Assembling Cages from Coiled-Coil Peptide Modules*
by Jordan M. Fletcher et al
"An ability to mimic the boundaries of biological compartments would improve our understanding of self-assembly and provide routes to new materials for the delivery of drugs and biologicals, and the development of protocells. We show that short designed peptides can be combined to form unilamellar spheres approximately 100 nanometers in diameter. The design comprises two, noncovalent, heterodimeric and homotrimeric coiled-coil bundles. These are joined back-to-back to render two complementary hubs, which when mixed form hexagonal networks that close to form cages. This design strategy offers control over chemistry, self-assembly, reversibility, and size of such particles." http://bit.ly/11SATOV
"The first synthetic DNA nanostructures were created by self-assembly of a small number of oligonucleotides. Introduction of the DNA origami method provided a new paradigm for designing and creating two- and three-dimensional DNA nanostructures by folding a large single-stranded DNA and ‘stapling’ it together with a library of oligonucleotides. Despite its power and wide-ranging implementation, the DNA origami technique suffers from some limitations. Foremost among these is the limited number of useful single-stranded scaffolds of biological origin. This report describes a new approach to creating large DNA nanostructures exclusively from synthetic oligonucleotides. The essence of this approach is to replace the single-stranded scaffold in DNA origami with a library of oligonucleotides termed “scaples” (scaffold staples). Scaples eliminate the need for scaffolds of biological origin and create new opportunities for producing larger and more diverse DNA nanostructures as well as simultaneous assembly of distinct structures in a “single-pot” reaction."
http://www.thesciencenetwork.org Richard Dawkins, J. Craig Venter, Nobel laureates Sidney Altman and Leland Hartwell, Chris McKay, Paul Davies, Lawrence Krau...
"Richard Dawkins, J. Craig Venter, Nobel laureates Sidney Altman and Leland Hartwell, Chris McKay, Paul Davies, Lawrence Krauss, and The Science Network's Roger Bingham discuss the origins of life, the possibility of finding life elsewhere, and the latest development in synthetic biology."
"In 1953, Watson and Crick not only described the double-helix structure of DNA, but also embraced the idea that genes contained a code that expresses information and thereby changed our view of life. This article traces how these ideas entered biological thinking and highlights the connections between different branches of science at the time, exploring the power of metaphor in science." http://bit.ly/11qmwB4
We should not forget Rosalind Franklin
She "is best known for her work on the X-ray diffraction images of DNA which led to the discovery of the DNA double helix. Her data, according to Francis Crick, were "the data we actually used" to formulate Crick and Watson's 1953 hypothesis regarding the structure of DNA. Franklin's images of X-ray diffraction confirming the helical structure of DNA were shown to Watson without her approval or knowledge. Though this image and her accurate interpretation of the data provided valuable insight into the DNA structure, Franklin's scientific contributions to the discovery of the double helix are often overlooked.." http://bit.ly/Kg2vU2
by Mannoor MS, Jiang Z, James T, Kong YL, Malatesta KA, Soboyejo W, Verma N, Gracias DH, McAlpine MC.
"The ability to three-dimensionally interweave biological tissue with functional electronics could enable the creation of bionic organs possessing enhanced functionalities over their human counterparts. However, current electronics are inherently two dimensional, preventing seamless multidimensional integration with biology as the processes and materials used to structure synthetic tissue constructs and conventional electronic devices are very different. Here, we present a novel strategy for overcoming these difficulties via additive manufacturing of biological cells with structural and nanoparticle derived electronic elements. As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the precise anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for the in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently connects to cochlear-like electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. Overall, our approach suggests a means to intricately merge biologic and nanoelectronic functionalities via 3D printing."
"Reconstituting an elementary gene expression system inside self-assembled lipid vesicles to mimic the cellular synthesis machinery is at the core of the development of a minimal cell following a bottom-up synthetic biology approach. The ability to operate the expression of multiple genes in a controlled manner and to generate the output proteins with predictable dynamics in liposomes relies on the link between genotype and phenotype. Here, we established this link in surface-tethered liposomes producing proteins from a linear DNA template using a reconstituted transcription/translation/aminoacylation apparatus fuelled by external supply of feedstock. The amounts of entrapped DNA molecules and synthesized proteins were visualized by fluorescence confocal microscopy in individual vesicles. We showed that there exists no linear correlation between the amount of encapsulated genes and the level of output proteins, which is a consequence of the compositional heterogeneity between liposomes due to the low-copy number of some constituents, as well as interfacing differences with the nutrient-containing environment. In order to decouple gene activity from those sources of variability and, thus, infer the probabilistic occupancy of transcriptionally active genes in protein synthesizing liposomes, we developed a dual gene expression assay consisting of the production of two fluorescent reporter proteins of distinguishable colors from two different DNA templates. The stochastic color-coding of the vesicles was analyzed and compared to the color pattern expected from a Poisson distribution of encapsulated genes. Unexpectedly, we found that the apparent number of transcriptionally active DNA molecules in liposomes corresponds only to ca. 10% of the bulk concentration. We believe that our study provides new insights about the relationship between the genotype and phenotype in protein synthesizing liposomes, which is of primary importance toward the construction of a programmable artificial cell implemented with regulatory gene networks of predictable dynamics." http://bit.ly/10vpfqp
A day after striking the latest in a series of its special "channel" collaborations, Intrexon has reloaded its bank account with a fresh $150 million infusion of cash, with significant added contributions from billionaire founder R.J.
"Pigeon is a Web-based tool that translates a textual description of a synthetic biology design into an image. It allows programmatic generation of design visualizations, is easy to learn, is easily extensible to new glyphs and notation, and can be connected to other software tools for visualizing their output. We present the Pigeon syntax, its current command set, and some examples of Pigeon programs and their output."
"The language of innovation often stresses disruption–eliminating inefficient industries and replacing them with more streamlined, technologically advanced versions. Nowhere is disruption more complex and important than in the energy industry, with implications for so much of the way that we live, affecting global industry, economics, and climate. A major focus of synthetic biology today is the design and production of biofuels, to disrupt the current practices of oil extraction and edge towards a more carbon-netural energy future. Biofuels have to disrupt not only the intricate complexity of cellular metabolic networks, but also the complex political, economic, and technological networks of global energy production. In the words of sociologist of science Adrian Mackenzie, “Biofuels, as it turns out, are extraordinarily messy entities to think with.”
In his recent paper “Synthetic biology and the technicity of biofuels” in the journal Studies in History and Philosophy of Biological and Biomedical Sciences, Mackenzie looks at three startup companies in the biofuels industry–Synthetic Genomics, Amyris, and Joule Unlimited–as case studies of how synthetic biology and biofuels “come into being, change and endure”, asking “how does synthetic biology translate a potential technical object into an actual technical object?”'
WASHINGTON – The number of private and public entities conducting research in synthetic biology worldwide grew significantly between 2009 and 2013, according to the latest version of an interactive map produced by the Synthetic Biology Project at ...
"The finite reservation of fossil fuels accelerates the necessity of development of renewable energy sources. Recent advances in synthetic biology encompassing systems biology and metabolic engineering enable us to engineer and/or create tailor made microorganisms to produce alternative biofuels for the future bio-era. For the efficient transformation of biomass to bioenergy, microbial cells need to be designed and engineered to maximize the performance of cellular metabolisms for the production of biofuels during energy flow. Toward this end, two different conceptual approaches have been applied for the development of platform cell factories: forward minimization and reverse engineering. From the context of naturally minimized genomes,non-essential energy-consuming pathways and/or related gene clusters could be progressively deleted to optimize cellular energy status for bioenergy production. Alternatively, incorporation of non-indigenous parts and/or modules including biomass-degrading enzymes, carbon uptake transporters, photosynthesis, CO2 fixation, and etc. into chassis microorganisms allows the platform cells to gain novel metabolic functions for bioenergy. This review focuses on the current progress in synthetic biology-aided pathway engineering in microbial cells and discusses its impact on the production of sustainable bioenergy."
Interview with George Church, Professor of Genetics at Harvard Medical School, where he discusses the Glowing Plant project and the potential of Synthetic Bi...
To tie in with this month’s SoNYC birthday celebrations,SpotOn is osting a collection of case studies that discuss how social media can be used for science outreach
Julia Percival answers
"Tell us a bit about you and your social media project Why did you decide to start this project? How did you get started and did you encounter any problems? What were the outcomes of your project? How did you assess whether the project was a success and whether it achieved your original goals? Did you unexpectedly achieve other things as well? List your five top tips for anyone wanting to start a similar project"
by Xingguo Liang *†‡, Mengguang Zhou †, Kenjiro Kato
"We demonstrated the generality of a strategy for photoswitching the activity of functional oligonucleotides by modulating their topological structure. Our strategy was proved to be versatile because it can be used to photoregulate functional oligonucleotides, e.g., ribozymes and DNAzymes, which have two binding arms and a catalytic loop. Repeated reversible photoregulation of RNA cleavage by a ribozyme or a DNAzyme was achieved by attaching two photoresponsive strands, artificial oligomers involving azobenzene moieties and nucleobases capable of forming a duplex as the supraphotoswitch. Individual strands were attached to the 3′ and 5′ ends of a RNA-cleavage oligonucleotide. Thus, the topological structure of the ribozyme or DNAzyme was constrained, and RNA cleavage was greatly suppressed when the supraphotoswitch duplex formed (OFF state). In contrast, RNA cleavage resumed when the supraphotoswitch duplex dissociated (ON state). Light irradiation was used to repeatedly switch the supraphotoswitch between the ON and OFF states so that RNA cleavage activity could be efficiently photoregulated. Analysis of the regulatory mechanism showed that topological constraints suppressed the RNA cleavage by causing both structural changes at the catalytic site and lower binding affinity between the RNA substrates and the functional oligonucleotides."
"Christina Agapakis is a rising star among the new generation of biology researchers. Trained in the science of custom-building organisms known as synthetic biology, the UCLA researcher likes to think about the way her field intersects with culture and industry more broadly.
Case in point: Through a program of the BioBricks Foundation, she worked with artist Sissel Tolaas to create cheeses cultured with the microbes that help produce our body odor. The project highlights the meaning that humans assign to the productions of the invisible world of bacteria. And Agapakis wants us to rethink our relationships with the microbial communities that live in and around us. "Re-contextualizing these ostensibly 'bad' smells, we saw that when the odor is in cheese it smells good and it's a sign of culture and good taste. But the same smell on a body is disgusting," she told me an interview for our most recent issue. "By making cheese using bacteria from the body, we're showing that we should be able to think about the microbes in our lives in different ways." Since the beginning of the 20th century, we've learned so much about the machinery that powers life, but the larger societal and political issues that the biosciences raise receive far less attention than technological developments like smartphones or social networks. Biology is so complex that we need people like Agapakis who provide pathways towards a better understanding of how we interact with all the life we can't see."
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by
Luo R, Ye L, Tao C, Wang K.
"Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called 'GeneCircuits', which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology."
http://bit.ly/100FQ9G