"Synthetic biology represents a recent attempt to bring engineering principles and practices to working with biology. In practice, the nature of the relationship between engineering and biology in synthetic biology is a subject of ongoing debate. The disciplines of biology and engineering are typically seen to involve different ways of knowing and doing, and to embody different assumptions and objectives. Tensions between these approaches are playing out as the field of synthetic biology is being established. Here, we study negotiations between engineering and biology through the International Genetically Engineered Machine (iGEM) competition. This undergraduate competition has been important in launching and bootstrapping the field of synthetic biology, and serves as a test-bed for the engineering approach. We show how a number of issues that iGEM teams must grapple with – including standardization, design, intellectual property, and the imagination of the social – involve the negotiation of engineering, biology, and other disciplines (including computer science), in ways more complex than the engineering rhetoric of synthetic biology implies. We suggest that a new moral economy for synthetic biology is being created, in which epistemic and institutional values, conventions, and practices are being negotiated and (re)defined."
"The emerging field of synthetic biology builds gene circuits for scientific, industrial and therapeutic needs. Adaptability of synthetic gene circuits across different organisms could enable a synthetic biology pipeline, where circuits are designed in silico, characterized in microbes and reimplemented in mammalian settings for practical usage. However, the processes affecting gene circuit adaptability have not been systematically investigated. Here we construct a mammalian version of a negative feedback-based 'linearizer' gene circuit previously developed in yeast. The first naïve mammalian prototype was non-functional, but a computational model suggested that we could recover function by improving gene expression and protein localization. After rationally developing and combining new parts as the model suggested, we regained function and could tune target gene expression in human cells linearly and precisely as in yeast. The steps we have taken should be generally relevant for transferring any gene circuit from yeast into mammalian cells."
Venue: Stata Center, MIT, Cambridge, Massachusetts, USA Date: Saturday morning, May 11 to Sunday noon May 12, 2013 Recognizing the fast emergence and potential significance of this field, the aim of this workshop is to bring together practitioners of mammalian synthetic biology together with experts from other relevant fields. The general goals of the workshop are to nucleate the nascent mammalian synthetic biology community, reach out to experts from other fields that can benefit from and contribute to this field, and define the important challenges and future directions. The workshop format will provide a forum for exposition of the latest developments in the field and discussions of how experts from other fields can benefit from and contribute to mammalian synthetic biology. Perhaps more importantly, the workshop will also include breakout sessions that will identify the main challenges and opportunities. Findings from the breakout sessions will be assembled into a written report that will be distributed to all workshop participants and to relevant government and funding agencies. The agenda on Saturday will include several 30 minute talks about mammalian synthetic biology tools and capabilities, talks about industrial and clinical applications, and two sets of breakout sessions. The first set of breakout sessions will focus on the technology, including large scale DNA assembly and integrationtranscriptional regulationsensors and actuatorsnon-transcriptional regulation.The second set of breakout sessions will focus on potential disease and scientific inquiry applications, including cancerstem cell and tissue engineeringvaccination and infectious diseasediabetes and metabolic diseasesdrug screening.The emphasis in these sessions will be on understanding and evaluating the transformative opportunities for synthetic biology in these areas. Sunday morning will include two talks and then reports from all breakout sessions. The workshop will end Sunday at noon. Organizing Committee: Ron Weiss, MIT, ChairPamela A. Silver, Harvard, Co-ChairNoubar Afeyan, Flagship VenturesJon Chesnut, Life TechnologiesGeorge M. Church, HarvardJames J. Collins, BULeonard Katz, SynBERCChristina D. Smolke, Stanford
"Color-tunable photonic fibers mimic the fruit of the "bastard hogberry" plant
A team of materials scientists at Harvard University and the University of Exeter, UK, have invented a new fiber that changes color when stretched. Inspired by nature, the researchers identified and replicated the unique structural elements that create the bright iridescent blue color of a tropical plant's fruit. The multilayered fiber, described today in the journal Advanced Materials, could lend itself to the creation of smart fabrics that visibly react to heat or pressure. "Our new fiber is based on a structure we found in nature, and through clever engineering we've taken its capabilities a step further," says lead author Mathias Kolle, a postdoctoral fellow at the Harvard School of Engineering and Applied Sciences (SEAS). "The plant, of course, cannot change color. By combining its structure with an elastic material, however, we've created an artificial version that passes through a full rainbow of colors as it's stretched."...."
*Expression of the sub-pathways of the Chloroflexus aurantiacus 3-hydroxypropionate carbon fixation bicycle in E. coli*
by Matthew Mattozzia, Marika Ziesacka, Mathias J. Vogesa Pamela A. Silvera, Jeffrey C. Waya
"The 3-hydroxypropionate (3-HPA) bicycle for CO2 fixation is unique among carbon-fixing systems in that none of its enzymes appear to be affected by oxygen. Moreover, the bicycle includes a number of enzymes that produce novel intermediates which may be of biotechnological interest, and the CO2-fixing steps in this pathway are relatively rapid. We therefore expressed portions of the 3-HPA bicycle in a heterologous organism, E. coli K12. We subdivided the 3-HPA bicycle into four sub-pathways: (1) synthesis of propionyl-CoA from acetyl-CoA, (2) synthesis of succinate from propionyl-CoA, (3) glyoxylate production and regeneration of acetyl-CoA, and (4) assimilation of glyoxylate and propionyl-CoA to form pyruvate and regenerate acetyl-CoA. We expressed the novel enzymes of the 3-HPA bicycle in operon form and used several phenotypic tests for activity. Sub-pathway 1 activated a propionate-specific biosensor. Sub-pathway 2, found in non-CO2-fixing bacteria, was reassembled in E. coli using genes from diverse sources. Sub-pathway 3, operating in reverse, generating succinyl-CoA sufficient to rescue a sucAD double mutant for its diaminopimelic acid (DAP) auxotrophy. Sub-pathway 4 was able to reduce the toxicity of propionate and allow propionate to contribute to cell biomass in a prpC-(2 methylcitrate synthase) mutant strain. These results indicate that all of the enzymes of the 3-HPA bicycle can function to some extent in vivo in a heterologous organism, as indicated by growth tests. Overexpression of certain enzymes was deleterious to cell growth, and, in particular, expression of MMC-CoA lyase caused a mucoid phenotype. These results have implications for metabolic engineering and for bacterial evolution through horizontal gene transfer."
"The notion of minimal cells refers to cellular structures that contain the minimal and sufficient complexity to still be defined as living, or at least capable to display the most important features of biological cells. Here we briefly describe the laboratory construction of minimal cells, a project within the broader field of synthetic biology. In particular we discuss the advancements in the preparation of semi-synthetic cells based on the encapsulation of biochemicals inside liposomes, illustrating from the one hand the origin of this research and the most recent developments; and from the other the difficulties and limits of the approach. The role of physicochemical understandings is greatly emphasized."
"By reproducing in the laboratory the complex interactions that cause human genes to turn on inside cells, Duke University bioengineers have created a system they believe can benefit gene therapy research and the burgeoning field of synthetic biology." http://bit.ly/14AyD0M
*Synergistic and tunable human gene activation by combinations of synthetic transcription factors*byPablo Perez-Pinera,David G Ousterout,Jonathan M Brunger,Alicia M Farin,Katherine A Glass,Farshid Guilak,Gregory E Crawford,Alexander J Hartemink& Charles A Gersbach http://bit.ly/XGvrwd
After Aaron, Reputation Metrics Startups Aim To Disrupt The Scientific Journal Industry by RICHARD PRICE
*SCIENTIFIC JOURNALS WILL DISAPPEAR*
"As I mentioned, the journal title has historically accounted for close to 100 percent of a scientist’s public reputation. That figure is probably now at 90 percent, with 10 percent for the new reputation metrics mentioned above. As new reputation metrics emerge, the journal title will decline in relative significance. Soon we will get to a point where the journal title contributes less than 10 percent of a scientist’s reputation, and the bulk of the scientist’s reputation metrics are coming from other sources.
The costs of publishing a paper via a journal are significant, both in impact and money. Journals take a long time to publish research. There is an average time lag of 12 months between submitting a paper to a journal, and the journal publishing it. This is 12 months of lost impact for the scientist. Journals mostly put papers behind paywalls, which further limits the audience and impact of the paper. Some journals now make the paper accessible to readers for free, but the author typically has to pay $1,000-$3,000 to remove the paywall around their research. Increasingly it will be seen as perverse to submit a paper to a journal and wait 12 months for comments from two scientists, instead of sharing it on a platform like Academia.edu and getting comments from hundreds of scientists in two weeks. The first journals to disappear will be the ones whose titles offer the least reputation boost – the second- and third-tier journals. Shortly afterwards, Nature, Science and the top-tier journals will disappear. Scientists will be sharing their work on multiple platforms, and their reputations will be based on a constellation of metrics. And as journals lose their significance, the dream of open access will be realized: a villager in India will have the same access to the world’s scientific literature as a professor at Harvard."
"This Behind the Scenes article was provided to LiveScience in partnership with the National Science Foundation. While your last interaction with bacteria may have been unpleasant, to say the least, synthetic biologists can't get enough of these stomach bugs. "Bacteria are great model systems for synthetic biology," says Chris Voigt, Ph.D., an associate professor in the Biological Engineering department at the Massachusetts Institute of Technology. "They are relatively simple organisms but we know so much about their genes...." http://bit.ly/XyMujS
*Perspectives on the Automatic Design of Regulatory Systems for Synthetic Biology*
by Guillermo Rodrigo, Javier Carrera, Thomas E. Landrain, Alfonso Jaramillo
"Automatic design is based on computational modeling and optimization methods to provide proto- type designs to targeted problems in an unsupervised manner. For biological circuits, we need to produce quantitative predictions of cell behavior for a given genotype as consequence of the differ- ent molecular interactions. Automatic design techniques aim at solving the inverse problem of find- ing the sequences of nucleotides that better fit a targeted behavior. In the post-genomic era, our molecular knowledge and modeling capabilities have allowed to start using such methodologies with success. Herein, we describe how the emergence of this new type of tools could enable novel synthetic biology applications. We highlight the essential elements to develop automatic design pro- cedures for synthetic biology pointing out their advantages and bottlenecks. We discuss in detail the experimental difficulties to overcome in the in vivo implementation of designed networks. The use of automatic design to engineer biological networks is starting to emerge as a new technique to per- form synthetic biology, which should not be neglected in the future."
James Chappell, Kirsten Jensen and Paul S. Freemont
"A bottleneck in our capacity to rationally and predictably engineer biological systems is the limited number of well-characterized genetic elements from which to build. Current characterization methods are tied to measurements in living systems, the transformation and culturing of which are inherently time-consuming. To address this, we have validated a completely in vitro approach for the characterization of DNA regulatory elements using Escherichia coli extract cell-free systems. Importantly, we demonstrate that characterization in cell-free systems correlates and is reflective of performance in vivo for the most frequently used DNA regulatory elements. Moreover, we devise a rapid and completely in vitro method to generate DNA templates for cell-free systems, bypassing the need for DNA template generation and amplification from living cells. This in vitro approach is significantly quicker than current characterization methods and is amenable to high-throughput techniques, providing a valuable tool for rapidly prototyping libraries of DNA regulatory elements for synthetic biology."
Expanding the Product Profile of a Microbial Alkane Biosynthetic Pathway
by Matthew Harger, Lei Zheng, Austin Moon, Casey Ager, Ju Hye An, Chris Choe, Yi-Ling Lai, Benjamin Mo, David Zong, Matthew D. Smith, Robert G. Egbert, Jeremy H. Mills, David Baker, Ingrid Swanson Pultz, and Justin B. Siegel
"Microbially produced alkanes are a new class of biofuels that closely match the chemical composition of petroleum-based fuels. Alkanes can be generated from the fatty acid biosynthetic pathway by the reduction of acyl-ACPs followed by decarbonylation of the resulting aldehydes. A current limitation of this pathway is the restricted product profile, which consists of n-alkanes of 13, 15, and 17 carbons in length. To expand the product profile, we incorporated a new part, FabH2 from Bacillus subtilis, an enzyme known to have a broader specificity profile for fatty acid initiation than the native FabH of Escherichia coli. When provided with the appropriate substrate, the addition of FabH2 resulted in an altered alkane product profile in which significant levels of n-alkanes of 14 and 16 carbons in length are produced. The production of even chain length alkanes represents initial steps toward the expansion of this recently discovered microbial alkane production pathway to synthesize complex fuels. This work was conceived and performed as part of the 2011 University of Washington international Genetically Engineered Machines (iGEM) project." http://bit.ly/11oAPcS
"In this paper we report on ethnographic work developed over two years, working as social scientists within a project on synthetic biology (SB), which aimed to use engineered bacteria as solutions to water industry problems. We were asked to help solve the ‘barrier to innovation’ by our engineering colleagues who believed that industrial and public ignorance would block their innovations. Instead of orienting around ‘ignorance’ we chose to explore the different ontologies of bacteria that were adopted in the various practices of the many sites involved in the project. We describe our observations in microbiological laboratories and compare them to a waste water treatment facility. Engineers in the lab understand bacteria as controllable but also vulnerable, thus their ability to manipulate and protect bacteria becomes important in their claims to expertise. In contrast, engineers in the water facility understand bacteria as dangerous, but they become skilled in protecting their bodies, make sense of their relation to bacteria through immunological narratives and claim expertise through an olfactory epistemology. Overall, we conclude that the ontologies of ‘engineer’ and ‘bacteria’ are interrelated through context-specific practices. Finally, we argue that this account is instructive for current policy and engagement discussions around SB."
"Learning Made Easier with Synthetic Biology Webinars Inquire, Understand, and Break Through to Discovery
At Life Technologies, we believe synthetic biology will change the way we create energy, produce food, optimize industrial processing, and detect, prevent, and cure diseases—improving the human condition and the world around us. We’re committed to offering unparalleled technology and solutions to the research community. With our platform of synthetic biology products, we intend to understand and answer some of life’s most challenging questions. Through design and engineering, our scientists enable researchers to study, alter, create, and re-create highly complex pathways, DNA sequences, genes, and natural biological systems. In the synthetic biology webinar series from Life Technologies, our scientists cover the different challenges that synthetic biology researchers encounter and address the solutions available to help them achieve their next breakthroughs.
Stay at the forefront of synthetic biology breakthroughs, register for a live webinar, or view our library of past webinars at your leisure. New webinars are added monthly, so subscribe now and be among the first to learn about the latest advances in synthetic biology research." http://bit.ly/XZNhsh
*A biological device made of DNA inserted into a bacterial cell works like a tiny diagnostic computer*
by Weizmann Institute of Science
"Scientists hope that one day in the distant future, miniature, medically-savvy computers will roam our bodies, detecting early-stage diseases and treating them on the spot by releasing a suitable drug, without any outside help. To make this vision a reality, computers must be sufficiently small to fit into body cells. Moreover, they must be able to “talk” to various cellular systems. These challenges can be best addressed by creating computers based on biological molecules such as DNA or proteins. The idea is far from outrageous; after all, biological organisms are capable of receiving and processing information, and of responding accordingly, in a way that resembles a computer.
Researchers at the Weizmann Institute of Science have recently made an important step in this direction: They have succeeded in creating a genetic device that operates independently in bacterial cells. The device has been programmed to identify certain parameters and mount an appropriate response. The device searches for transcription factors – proteins that control the expression of genes in the cell. A malfunction of these molecules can disrupt gene expression. In cancer cells, for example, the transcription factors regulating cell growth and division do not function properly, leading to increased cell division and the formation of a tumor. The device, composed of a DNA sequence inserted into a bacterium, performs a “roll call” of transcription factors. If the results match preprogrammed parameters, it responds by creating a protein that emits a green light – supplying a visible sign of a “positive” diagnosis. In follow-up research, the scientists – Prof. Ehud Shapiro and Dr. Tom Ran of the Biological Chemistry and Computer Science and Applied Mathematics Departments – plan to replace the light-emitting protein with one that will affect the cell’s fate, for example, a protein that can cause the cell to commit suicide. In this manner, the device will cause only “positively” diagnosed cells to self-destruct. In the present study, published in Nature's Scientific Reports, the researchers first created a device that functioned like what is known in computing as a NOR logical gate: It was programmed to check for the presence of two transcription factors and respond by emitting a green light only if both were missing. When the scientists inserted the device into four types of genetically engineered bacteria – those making both transcription factors, those making none of the transcription factors, and two types making one of the transcription factors each – only the appropriate bacteria shone green. Next, the research team – which also included graduate students Yehonatan Douek and Lilach Milo – created more complex genetic devices, corresponding to additional logical gates. Following the success of the study in bacterial cells, the researchers are planning to test ways of recruiting such bacteria as an efficient system to be conveniently inserted into the human body for medical purposes (which shouldn’t be a problem; recent research reveals there are already 10 times more bacterial cells in the human body than human cells). Yet another research goal is to operate a similar system inside human cells, which are much more complex than bacteria."
Boston Children's Hospital's blog about science, research, and clinical innovation in pediatric and adult medicine.
Gerd Moe-Behrens's insight:
by TOM ULRICH
"They don’t look like much sitting in your hand. A few pieces of clear plastic, each smaller than an Altoids tin, with channels visible inside and holes for plugging tubing into them.
But fill them with cells and treat those cells the right way, and they turn into something amazing: tiny hearts, lungs, guts, kidneys. They’re “organs on chips,” and they represent what’s probably the most comprehensive effort to date to physically model the functions of whole organs for drug development and disease research. Developed by a team of biologists and engineers led by Donald Ingber, MD, PhD, a member of Boston Children’s Hospital’s Vascular Biology Program and director of the Wyss Institute for Biologically Inspired Engineering at Harvard, they’re the building blocks for an ambitious project to create an artificial multi-organ system—essentially, a whole body on a chip....."
"Combining microfabrication techniques with modern tissue engineering, lung-on-a-chip offers a new in vitro approach to drug screening by mimicking the complicated mechanical and biochemical behaviors of a human lung. This version of the video (updated January 29, 2013) includes our findings when we mimicked pulmonary edema on the chip. Watch this video to see how it works." http://hvrd.me/YaXt1M
"“Robustness”, the network ability to maintain systematic performance in the face of intrinsic perturbations, and “response ability”, the network ability to respond to external stimuli or transduce them to downstream regulators, are two important complementary system characteristics that must be considered when discussing biological system performance. However, at present, these features cannot be measured directly for all network components in an experimental procedure. Therefore, we present two novel systematic measurement methods – Network Robustness Measurement (NRM) and Response Ability Measurement (RAM) – to estimate the network robustness and response ability of a gene regulatory network (GRN) or protein-protein interaction network (PPIN) based on the dynamic network model constructed by the corresponding microarray data. We demonstrate the efficiency of NRM and RAM in analyzing GRNs and PPINs, respectively, by considering aging- and cancer-related datasets. When applied to an aging-related GRN, our results indicate that such a network is more robust to intrinsic perturbations in the elderly than in the young, and is therefore less responsive to external stimuli. When applied to a PPIN of fibroblast and HeLa cells, we observe that the network of cancer cells possesses better robustness than that of normal cells. Moreover, the response ability of the PPIN calculated from the cancer cells is lower than that from healthy cells. Accordingly, we propose that generalized NRM and RAM methods represent effective tools for exploring and analyzing different systems-level dynamical properties via microarray data. Making use of such properties can facilitate prediction and application, providing useful information on clinical strategy, drug target selection, and design specifications of synthetic biology from a systems biology perspective."
by Pablo Perez-Pinera,David G Ousterout,Jonathan M Brunger,Alicia M Farin,Katherine A Glass,Farshid Guilak,Gregory E Crawford,Alexander J Hartemink& Charles A Gersbach
"Mammalian genes are regulated by the cooperative and synergistic actions of many transcription factors. In this study we recapitulate this complex regulation in human cells by targeting endogenous gene promoters, including regions of closed chromatin upstream of silenced genes, with combinations of engineered transcription activator–like effectors (TALEs). These combinations of TALE transcription factors induced substantial gene activation and allowed tuning of gene expression levels that will broadly enable synthetic biology, gene therapy and biotechnology."
"Three billion years after inanimate chemistry first became animate life, a newly synthesized laboratory compound is behaving in uncannily lifelike ways.
The particles aren’t truly alive — but they’re not far off, either. Exposed to light and fed by chemicals, they form crystals that move, break apart and form again. “There is a blurry frontier between active and alive,” said biophysicist Jérémie Palacci of New York University. “That is exactly the kind of question that such works raise.” Palacci and fellow NYU physicist Paul Chaikin led a group of researchers in developing the particles, which are described Jan. 31 in Science as forming “living crystals” in the right chemical conditions. Their experiments are rooted in the researchers’ interest in self-organizing collective behaviors, which are easier to study in controlled particle form than in schooling fish or flocking birds. Each particle is made from a microscopic cube of hematite, a compound consisting of iron and oxygen, sheathed in a spherical polymer coat. One corner is left exposed. Under certain wavelengths of blue light, hematite conducts electricity. When the particles are placed in a hydrogen peroxide bath under blue light, chemical reactions catalyze around the exposed tips."
by Nicole Kronberger, Peter Holtz and Wolfgang Wagner
"Whenever a new, potentially controversial technology enters public aware-ness, stakeholders suggest that education and public engagement are needed toensure public support. Both theoretical and empirical analyses suggest, how-ever, that more information and more deliberation per se will not make peoplemore supportive. Rather, taking into account the functions of public sense-making processes, attitude polarisation is to be expected. In a real-worldexperiment, this study on synthetic biology investigated the effect of informa-tion uptake and deliberation on opinion certainty and opinion valence in natu-ral groups. The results suggest (a) that biotechnology represents an importantanchor for sense-making processes of synthetic biology, (b) that real-worldinformation uptake and deliberation make people feel more certain about their opinions, and (c) that group attitudes are likely to polarise over the course of deliberation if the issue is important to the groups." http://bit.ly/11ApHVY
"In his recent ‘Tomorrow’s World’ speech at the Policy Exchange, the Right Honorable David Willetts MP, Minister for Universities and Science sets out a vision for how the UK could become a world leader in eight future technologies (building on the Chancellor’s speech at the Royal Society in November). These technologies will receive an extra £600m of funding as announced in last year’s Autumn Statement.
This week I attended a workshop on synthetic biology (one of the eight technologies set out by the Minister – receiving £88m) at Imperial College, under the auspices of the US National Academy of Sciences’ Committee on Science, Technology, and Law. The 20 or so participants, drawn from academia, industry, policy and the legal community were tasked with assessing the demand for international discussion on ownership and sharing issues that may impede research and prospects for commercialisation. For example, the participants discussed if existing patent regimes are fit for purpose and how/if to respond to options for achieving global standards (for example in data exchange, units of measurement and registering parts and devices). Naturally differences between patent systems (e.g. in the US, UK/EU and China), result in mixed views. For example the UK and EU systems offer academic exclusions from patent infringement that are not available under US jurisdiction. But some UK researchers still feel strongly that existing patent regimes impose major barriers to achieving the commercialisation and economic growth potential that synthetic biology offers. Whether these barriers are new and specific to synthetic biology also raises mixed views. On the one hand, some argue the design principles of synthetic biology leave researchers particularly prone to a perfect storm of excessive costs through patent stacking, unintentional infringement and patent hold-up (see discussion on ownership and sharing available here for more on this). On the other hand, others argue that the issues are not new; yes the system(s) may be imperfect, but they are far from completely broken, and may in fact offer some advantages… It is true that synthetic biology is a still an emerging field and there are few examples of case law to help us assess if fears are real or imagined. But research is also moving very fast and expectations for commercialisation are growing. In the meantime, we can expect to go through a few growing pains as research progresses through to adolescence (if not maturation) and the debates should continue to bring in a wide range of expertise and perspectives."
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