by Zhengjun Guan ; Lei Pei ; Markus Schmidt ; Wei Wei "While having developed into one of the most dynamic fields of the life sciences, synthetic biology may pose potential risks to the environment and human health. Based on current national and international risk assessment methods and current regulation of synthetic biology, we reviewed risk assessment in relation to synthetic biology’s research subfields (such as DNA-based biocircuits, minimal genome, protocells and chemical synthetic biology), its relation with biosafety engineering, its effect on ELSI (Ethics, Legal and Social Implications) and recent biosecurity challenges, such as biopunk (or biohackery), garage biology, do-it-yourself biology and bioterrorism. Additionally, we investigated existing strategies for management of synthetic biology research, focusing on self-regulatory or technology-focused methods and using the 5P (the principal investigator, the project, the premises, the provider of genetic material and its purchaser) strategy focusing in five different policy intervention points. Furthermore, we reviewed the current research and development of synthetic biology and its current biosafety regulations in China. Finally, we recommended management strategies to guide future research in synthetic biology with necessary amendments, including the establishment of regulations with a core of safety assessment, synthetic biology-specific good laboratory practice guidelines, and arguments for the reinforcement of internal regulation at the institution level and more active public outreach efforts for biosafety." http://www.doaj.org/doaj?func=abstract&id=1027935
DNA synthesis, assembly and applications in synthetic biology
by Ma S, Tang N, Tian J. "The past couple of years saw exciting new developments in microchip-based gene synthesis technologies. Such technologies hold the potential for significantly increasing the throughput and decreasing the cost of gene synthesis. Together with more efficient enzymatic error correction and genome assembly methods, these new technologies are pushing the field of synthetic biology to a higher level." http://1.usa.gov/LDsxEX
Shuler ML, Foley P, Atlas J. "One important aim of synthetic biology is to develop a self-replicating biological system capable of performing useful tasks. A mathematical model of a synthetic organism would greatly enhance its value by providing a platform in which proposed modifications to the system could be rapidly prototyped and tested. Such a platform would allow the explicit connection of genomic sequence information to physiological predictions. As an initial step toward this aim, a minimal cell model (MCM) has been formulated. The MCM is defined as a model of a hypothetical cell with the minimum number of genes necessary to grow and divide in an optimally supportive culture environment. It is chemically detailed in terms of genes and gene products, as well as physiologically complete in terms of bacterial cell processes (e.g., DNA replication and cell division). A mathematical framework originally developed for modeling Escherichia coli has been used to build the platform MCM. A MCM with 241 product-coding genes (those which produce protein or stable RNA products) is presented. This gene set is genomically complete in that it codes for all the functions that a minimal chemoheterotrophic bacterium would require for sustained growth and division. With this model, the hypotheses behind a minimal gene set can be tested using a chemically detailed, dynamic, whole-cell modeling approach. Furthermore, the MCM can simulate the behavior of a whole cell that depends on the cell's (1) metabolic rates and chemical state, (2) genome in terms of expression of various genes, (3) environment both in terms of direct nutrient starvation and competitive inhibition leading to starvation, and (4) genomic sequence in terms of the chromosomal locations of genes." http://1.usa.gov/JSYSTM
"The study of genome size (GS) and its variation is so fascinating to the scientific community because it constitutes the link between the present-day analytical and molecular studies of the genome and the old trunk of the holistic and synthetic view of the genome. The GS of several taxa vary over a broad range and do not correlate with the complexity of the organisms (the C-value paradox). However, the biology of transposable elements has let us reach a satisfactory view of the molecular mechanisms that give rise to GS variation and novelties, providing a less perplexing view of the significance of the GS (C-enigma). The knowledge of the composition and structure of a genome is a pre-requisite for trying to understand the evolution of the main genome signature: its size. The radiation of mammals provides an approximately 180-million-year test case for theories of how GS evolves. It has been found from data-mining GS databases that GS is a useful cyto-taxonomical instrument at the level of orders/superorders, providing genomic signatures characterizing Monotremata, Marsupialia, Afrotheria, Xenarthra, Laurasiatheria, and Euarchontoglires. A hypothetical ancestral mammalian-like GS of 2.9-3.7 pg has been suggested. This value appears compatible with the average values calculated for the high systematic levels of the extant Monotremata (∼2.97 pg) and Marsupialia (∼4.07 pg), suggesting invasion of mobile DNA elements concurrently with the separation of the older clades of Afrotheria (∼5.5 pg) and Xenarthra (∼4.5 pg) with larger GS, leaving the Euarchontoglires (∼3.4 pg) and Laurasiatheria (∼2.8 pg) genomes with fewer transposable elements. However, the paucity of GS data (546 mammalian species sized from 5,488 living species) for species, genera, and families calls for caution. Considering that mammalian species may be vanished even before they are known, GS data are sorely needed to phenotype the effects brought about by their variation and to validate any hypotheses on GS evolution in mammals."
Pawelczyk S, Scott KA, Hamer R, Blades G, Deane CM, Wadhams GH.
"Phosphosignalling pathways are an attractive option for the synthetic biologist looking for a wide repertoire of modular components from which to build. We demonstrate that two-component systems can be used in synthetic biology. However, their potential is limited by the fact that host cells contain many of their own phosphosignalling pathways and these may interact with, and cross-talk to, the introduced synthetic components. In this paper we also demonstrate a simple bioinformatic tool that can help predict whether interspecies cross-talk between introduced and native two-component signalling pathways will occur and show both in vitro and in vivo that the predicted interactions do take place. The ability to predict potential cross-talk prior to designing and constructing novel pathways or choosing a host organism is essential for the promise that phosphosignalling components hold for synthetic biology to be realised."
Richard Van Noorden "Ethanol has dominated the biofuel industry’s attention over the past few years. But synthetic-biology companies are now scaling up production of what some say is a superior fuel: butanol, an alcohol with four carbon atoms to ethanol’s two. Compared to ethanol, butanol stores more energy per litre, is less corrosive to pipelines, is more easily separated from water and can be blended into gasoline (petrol) at higher concentrations before vehicle engines are damaged....." http://bit.ly/KLDmQC
Dongsheng Li, Michael H. Nielsen, Jonathan R. I. Lee, Cathrine Frandsen, Jillian F. Banfield, James J. De Yoreo "The oriented attachment of molecular clusters and nanoparticles in solution is now recognized as an important mechanism of crystal growth in many materials, yet the alignment process and attachment mechanism have not been established. We performed high-resolution transmission electron microscopy using a fluid cell to directly observe oriented attachment of iron oxyhydroxide nanoparticles. The particles undergo continuous rotation and interaction until they find a perfect lattice match. A sudden jump to contact then occurs over less than 1 nanometer, followed by lateral atom-by-atom addition initiated at the contact point. Interface elimination proceeds at a rate consistent with the curvature dependence of the Gibbs free energy. Measured translational and rotational accelerations show that strong, highly direction-specific interactions drive crystal growth via oriented attachment." http://bit.ly/LjFWll
"Embryologists have classically approached the ideas in Turing's "The chemical basis of morphogenesis" in two ways: (a) they have modelled embryos in silico to see if Turing patterning could make a particular pattern in principle; and (b) they have sought evidence, from gene expression patterns and knockout phenotypes, for Turing patterning in vivo.
We are taking a third approach, effectively a hybrid of the other two and of synthetic biology: we seek to assemble a synthetic Turing patterning system in cultures of living cells. Here, we will present our design, how it behaves in models, and will describe the state of our construction at the time of the meeting.
Presented by Professor Jamie Davies, Physiology Department, the University of Edinburgh
Recorded on Friday 11 May 2012 at the Informatics Forum, The University of Edinburgh.
The Turing Research Symposium was organised by the Royal Society of Edinburgh and the University of Edinburgh School of Informatics in partnership with SICSA and supported by Cambridge University Press." http://bit.ly/JJMjtV
A team of researchers at the Council for Scientific and Industrial Research (CSIR) is the first in Africa to establish groundbreaking biomedical stem cell technology, which could hold the key to finding cures for some of Africa’s most prevalent...
BY WILL MENDELSON "Keith Tyo specializes in synthetic biology, engineering cells that can provide inexpensive diagnosis and treatment for disease.
Keith Tyo applies synthetic biology - genetically reprogramming cells - to combat global health crises such as malaria.
Malaria strikes nearly 500 million people and causes a million deaths every year, according to the World Health Organization.
Tyo, a chemical and biological engineer at Northwestern University, recently received a $100,000 grant from the Bill & Melinda Gates Foundation for his work. His global health projects focus on creating new compounds to treat a host of diseases, including HIV and tuberculosis. He plans to produce low-cost biosensors for underprivileged countries desperately in need of basic medical diagnostic equipment....."
Just read this statement by +Eric Schmidt in wired uk http://www.wired.co.uk/news/archive/2012-05/23/eric-schmidt-science-education "the scientific method of hypothesise, test, revise and repeat must remain paramount", adding "careful and repeatable experimentation is the crux of science". I see this quite different: contemporary “science” has moved from the hypothesis method as it fail in respect to the challenges we face today. We have a paradigm change form hypothesis to data driven science. A reductionistic science moves to a holistic systemics (for review see: http://www.leukippos.org/Leukippos_Institute/Video.html ) This is a complicated question to answer and requires knowledge in history of philosophy, formal logic and philosophy of science. The cited review gives you a brief introduction to this subject. Some of the major points: The hypothesis method is reductionistic. It can deal with single correlations, but not with complex systems, because it is impossible to deduce an empirical consequence in multi factor systems. Our move into the digital age has also fundamental impact on the way we perform science. The enormous amount of data we have online access to, has a fundamental impact on the science paradigm. We have now access to huge data amounts, which build complex data systems. This data flooding problem can not be solved by normal science. The hypothesis method failed in this context. Contemporary research has come to a point where we change the perspective from reduction to holism. The reductionistic approach has successfully identified many components and interactions, but does not provide convincing explanation for how a complex system, such as a living being work. Today we are in the situation that we have huge amounts of data from high throughput experiments, but we do not understand the whole picture. Moreover, huge amounts of data and facts available mean lesser need for models. The word science has it’s indo-european root in the word scy. This means separating. Scy belongs to a reductionistic world of thinking. Science is a synonym with reductionism based on a materialistic concept. Heinz Foerster (1911-2002), an architect of cybernetics, saw an end to a 2000 years movement started with Aristotle. He stated: “If you take in account all system theory and systems researchers, which appear today in art and science I would not call this science any longer I would call it systemics. Contemporary science moved to a position, which sees thing together, short systemics. Thus: From science to systemics. This is how I see the steps today.” Beside Norbert Wiener, William Ross Ashby, and Ludwig Bertalanffy is Heinz Foerster one of the key figures, who developed a new theory for dealing with huge data amounts and complex systems: Systems Theory. Systems theory is the basis for Systems Biology and it’s practical application Synthetic Biology, two key sciences of the 21st century which already have moved form the hypothesis method to sytemics.
Katherine A Riccione, Robert P Smith, Anna J Lee, and Lingchong You "The survival of cells and organisms requires proper responses to environmental signals. These responses are governed by cellular networks, which serve to process diverse environmental cues. Biological networks often contain recurring network topologies called ‘motifs’. It has been recognized that the study of such motifs allows one to predict the response of a biological network, and thus cellular behavior. However, studying a single motif in complete isolation of all other network motifs in a natural setting is difficult. Synthetic biology has emerged as a powerful approach to understanding the dynamic properties of network motifs. In addition to testing existing theoretical predictions, construction and analysis of synthetic gene circuits has led to the discovery of novel motif dynamics such as how the combination of simple motifs can lead to autonomous dynamics or how noise in transcription and translation can affect the dynamics of a motif. Here, we review developments in synthetic biology as they pertain to increasing our understanding of cellular information processing. We highlight several types of dynamic behaviors that diverse motifs can generate, including the control of input/output responses, the generation of autonomous spatial and temporal dynamics, as well as the influence of noise in motif dynamics and cellular behavior."
"We analyzed DNA microarrays to identify highly expressed genes during stationary phase of Synechocystis sp. PCC 6803. Many identified genes are on endogenous plasmids, with copy numbers between 0.4 and 7 per chromosome. The promoters of such genes will be useful parts for synthetic biology applications in this phototrophic host."
Logic gates based on ion transistors by Klas Tybrandt, Robert Forchheimer & Magnus Berggren "Precise control over processing, transport and delivery of ionic and molecular signals is of great importance in numerous fields of life sciences. Integrated circuits based on ion transistors would be one approach to route and dispense complex chemical signal patterns to achieve such control. To date several types of ion transistors have been reported; however, only individual devices have so far been presented and most of them are not functional at physiological salt concentrations. Here we report integrated chemical logic gates based on ion bipolar junction transistors. Inverters and NAND gates of both npn type and complementary type are demonstrated. We find that complementary ion gates have higher gain and lower power consumption, as compared with the single transistor-type gates, which imitates the advantages of complementary logics found in conventional electronics. Ion inverters and NAND gates lay the groundwork for further development of solid-state chemical delivery circuits." http://bit.ly/KqX9tf
"Chirality is absolutely central in chemistry and biology. The recent findings of chiral self-assembling peptides' remarkable chemical complementarity and structural compatibility make it one of the most inspired designer materials and structures in nanobiotechnology. The emerging field of designer chemistry and biology further explores biological and medical applications of these simple d,l- amino acids through producing marvellous nanostructures under physiological conditions. These self-assembled structures include well-ordered nanofibers, nanotubes and nanovesicles. These structures have been used for 3-dimensional tissue cultures of primary cells and stem cells, sustained release of small molecules, growth factors and monoclonal antibodies, accelerated wound-healing in reparative and regenerative medicine as well as tissue engineering. Recent advances in molecular designs have also led to the development of 3D fine-tuned bioactive tissue culture scaffolds. They are also used to stabilize membrane proteins including difficult G-protein coupled receptors for designing nanobiodevices. One of the self-assembling peptides has been used in human clinical trials for accelerated wound-healings. It is our hope that these peptide materials will open doors for more and diverse clinical uses. The field of chiral self-assembling peptide nanobiotechnology is growing in a number of directions that has led to many surprises in areas of novel materials, synthetic biology, clinical medicine and beyond."
Yadav VG, De Mey M, Lim CG, Ajikumar PK, Stephanopoulos G.
"Industrial biotechnology promises to revolutionize conventional chemical manufacturing in the years ahead, largely owing to the excellent progress in our ability to re-engineer cellular metabolism. However, most successes of metabolic engineering have been confined to over-producing natively synthesized metabolites in E. coli and S. cerevisiae. A major reason for this development has been the descent of metabolic engineering, particularly secondary metabolic engineering, to a collection of demonstrations rather than a systematic practice with generalizable tools. Synthetic biology, a more recent development, faces similar criticisms. Herein, we attempt to lay down a framework around which bioreaction engineering can systematize itself just like chemical reaction engineering. Central to this undertaking is a new approach to engineering secondary metabolism known as 'multivariate modular metabolic engineering' (MMME), whose novelty lies in its assessment and elimination of regulatory and pathway bottlenecks by re-defining the metabolic network as a collection of distinct modules. After introducing the core principles of MMME, we shall then present a number of recent developments in secondary metabolic engineering that could potentially serve as its facilitators. It is hoped that the ever-declining costs of de novo gene synthesis; the improved use of bioinformatic tools to mine, sort and analyze biological data; and the increasing sensitivity and sophistication of investigational tools will make the maturation of microbial metabolic engineering an autocatalytic process. Encouraged by these advances, research groups across the world would take up the challenge of secondary metabolite production in simple hosts with renewed vigor, thereby adding to the range of products synthesized using metabolic engineering."
Jane Calvert "Synthetic biology is in the process of inventing itself and its ownership regimes. There are currently two dominant approaches to ownership and sharing in the field. The work of the J. Craig Venter Institute is grounded in molecular biology and in gene patenting. Parts-based approaches to synthetic biology, in contrast, are inspired by engineering, open source software and distributed innovation, and they are building new communities to help further this agenda. Despite these differences, the two approaches make very similar use of informational and computational metaphors. They both also have a place in a vision for the future of synthetic biology as a ‘diverse ecology’ of the open and the proprietary. It remains to be seen whether such a diverse ecology will be sustainable, whether synthetic biology will go down the patenting route taken by previous biotechnologies or whether different forms of ownership and sharing will emerge. Which path is taken will depend on the success of synthetic biology in achieving both its technical objectives and its social innovations." http://bit.ly/JCQVs0
"In the fields of proteomics, metabolic engineering and synthetic biology there is a need for high-throughput and reliable cloning methods to facilitate construction of expression vectors and genetic pathways. Here, we describe a new approach for solid-phase cloning in which both the vector and the gene are immobilized to separate paramagnetic beads and brought into proximity by magnetic force. Ligation events were directly evaluated using fluorescent-based microscopy and flow cytometry. The highest ligation efficiencies were obtained when gene- and vector-coated beads were brought into close contact by application of a magnet during the ligation step. An automated procedure was developed using a laboratory workstation to transfer genes into various expression vectors and more than 95% correct clones were obtained in a number of various applications. The method presented here is suitable for efficient subcloning in an automated manner to rapidly generate a large number of gene constructs in various vectors intended for high throughput applications."
"In April, the White House released a policy paper what was styled the "National Bioeconomy Blueprint." Its presumptions are based on the idea that the portion of the economy "fueled by research and innovation in the biological sciences" is a "large and rapidly growing segment of the world economy that provides substantial public benefit." This has caused innovation in the biological sciences to become a priority of the Obama Administration, promising not only economic development but to "live longer, healthier lives, reduce our dependence on oil, address key environmental challenges, transform manufacturing processes, and increase the productivity and scope of the agricultural sector while growing new jobs and industries." Successes of the bioeconomy touted by the Blueprint include $76 billion in revenues from genetically engineered crops and $100 billion in revenues from "industrial biotechnology" (including "fuels, materials, chemicals, and industrial enzymes derived from genetically modified systems"). The Blueprint identifies genetic engineering technology, DNA sequence analysis and "automated high-throughput manipulations of biomolecules" as "foundational technologies," while identifying "synthetic biology," proteomics and bio-informatics as "emerging technologies."
The result of the "bioeconomy" becoming an Administration "priority" is a directive (Executive Memorandum (M-10-30)) to all Federal agencies to "support research to establish the foundations for a 21st century bioeconomy," an effort that the Blueprint says has made "significant early progress." While these efforts also "raise important ethical and security issues that are also top priorities for the Administration," discussions of these concerns are expressly deemed to be outside the scope of the Blueprint itself.
The first chapter of the Blueprint sets out the broad goals, citing the National Research Council's 2009 report, A New Biology for the 21st Century, ...."
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