"Synthetic regulatory networks with prescribed functions are engineered by assembling a reduced set of functional elements. We could also assemble them computationally if the mathematical models of those functional elements were predictive enough in different genetic contexts. Only after achieving this will we have libraries of models of biological parts able to provide predictive dynamical behaviors for most circuits constructed with them. We thus need tools that can automatically explore different genetic contexts, in addition to being able to use such libraries to design novel circuits with targeted dynamics. We have implemented a new tool, AutoBioCAD, aimed at the automated design of gene regulatory circuits. AutoBioCAD loads a library of models of genetic elements and implements evolutionary design strategies to produce (i) nucleotide sequences encoding circuits with targeted dynamics that can then be tested experimentally and (ii) circuit models for testing regulation principles in natural systems, providing a new tool for synthetic biology. AutoBioCAD can be used to model and design genetic circuits with dynamic behavior, thanks to the incorporation of stochastic effects, robustness, qualitative dynamics, multiobjective optimization, or degenerate nucleotide sequences, all facilitating the link with biological part/circuit engineering."
"Synthetic biology has recently been at the center of the world’s attention as a new scientific and engineering discipline. It allows us to design and construct finely controllable metabolic and regulatory pathways, circuits, and networks, as well as create new enzymes, pathways, and even whole cells. With this great power of synthetic biology, we can develop new organisms that can efficiently produce new drugs to benefit human healthcare and superperforming microorganisms capable of producing chemicals, fuels, and materials from renewable biomass, without the use of fossil oil. Based on several successful examples reported, this commentary aims at peeking into the potential of synthetic biology."
"The latest episode in the American Chemical Society's (ACS') award-winning Global Challenges/Chemistry Solutions podcast series describes bacteria that are "addicted" to caffeine in a way that promises practical uses ranging from decontamination of wastewater to bioproduction of medications for asthma.Based on a report by Jeffrey Barrick, Ph.D., and colleagues in the journal ACS Synthetic Biology, the new podcast is available without charge at iTunes and from http://www.acs.org/globalchallenges.Some people may joke about living on caffeine, but scientists now have genetically engineered E. coli bacteria to do that—literally.Barrick and colleagues note that caffeine and related chemical compounds have become important water pollutants due to widespread use in coffee, soda pop, tea, energy drinks, chocolate and certain medications. These include prescription drugs for asthma and other lung diseases.The scientists knew that a natural soil bacterium, Pseudomonas putida CBB5, can actually live solely on caffeine and could be used to clean up such environmental contamination. So they set out to transfer genetic gear for breaking down caffeine from P. putida into that old workhorse of biotechnology, E. coli, which is easy to handle and grow.The study reports their success in doing so, as well as use of the E. coli for decaffeination and measuring the caffeine content of beverages. It describes development of a synthetic packet of genes for breaking down caffeine and related compounds that can be moved easily to other microbes. When engineered into certain E. coli, the result was bacteria literally addicted to caffeine.The genetic packet could have applications beyond environmental remediation, the scientists say, citing potential use as a sensor to measure caffeine levels in beverages, in recovery of nutrient-rich byproducts of coffee processing and for the cost-effective bioproduction of medicines..."
Robert F. Service "Electronic components are invading the body. In the lab, cling wrap–like circuitry draped over the hearts of test animals can track the activity of each of the heart's four chambers and kill tissue that initiate potentially deadly arrhythmias. Other arrays penetrate brain tissue to monitor the abnormal nerve firing patterns in epilepsy or induce gene expression in the brain tissue of mice. One team has even made a 3D printed bionic ear able to pick up ultrasonic bleats that humans cannot hear. These early prototypes can't produce science-fiction cyborgs; most are used in medicine. But over time, expect devices that will make us better athletes and soldiers, or even improve our complexions."
*The exhibition “Yours Synthetically” is all about the thematic topic of synthetic biology*
by MARTIN HIESLMAIR
"Mr. Gardiner, as we are doing this interview you are collecting artistic works for the next exhibition at the Ars Electronica Center with the English title called “Yours Synthetically” that deals with synthetic biology. Why is this topic so relevant for us nowadays?
If we look at it purely from the scientific point of view we can say that even from Robert Hooke who used the microscope to discover the cell, the science of biology has continually developed alongside new technologies. The discovery of the double helix and the structure of DNA and all the other milestones of scientific progresses led to the understanding that we could cut and paste genetic information from one organism to another. Early genetic experiments progressed to experiments by modern biologist like Craig Venter, who took a synthetic genome put it into a cell and replaced the old genome that was in the cell, and it started to reproduce. They then examined the new cells and discovered that the synthetic genome had completely replaced the organic one. So to use the computer metaphor – which is quite popular in these studies – we took the hardware of the cell and we changed the software. For a biologist this is very crude. This idea of synthetic biology being an engineering approach to nature – what people find quite frightening – actually is too simplistic. Engineering implies that you know everything that can happen, like you would know that a building will stand even in an earthquake. But how can a synthetic biologist or engineer know what impact of this very long sequence can have on the organism, on the whole environment? The word engineering was kind of being cut out because many people were quite afraid of this – genetic engineering if you remember is what’s called during the past decades. Synthetic biology is partly an attempt by science to reframe this whole field and separate it from the public relations disaster of Genetic Engineering....."
The future scientist will do coding and designing abstraction. Lab work is will be done by robots or outsourced.....
*A growing number of biotechnology companies employ a skeleton crew of managers and outsource hands-on science.*
Biotechnology: Virtual reality by Heidi Ledford
"If Rosana Kapeller has her way, her company will develop treatments for scourges such as cancer, cardiovascular disease and diabetes. And it will do so with only 12 full-time employees and no wet labs.
Kapeller shares a quiet office with eight colleagues at the headquarters of Nimbus Discovery in Cambridge, Massachusetts. The rest work from their homes in Missouri, Connecticut, Rhode Island and New York. This skeleton crew manages the company's operations and computer analyses; all hands-on experiments are outsourced to an international assembly of contract-research organizations (CROs). “It's a lot like managing a lab down the hall,” says Kapeller, the company's chief scientific officer. “But instead of down the hall, the lab's in China and we're using Skype.” Such is life at a 'virtual' biotechnology company, a lean, nimble model that is gaining popularity among cash-hungry start-ups. These companies consist of as few as one full-time employee who oversees a drug from preclinical development to tests in patients, all in the hands of outside contractors. To take advantage of this niche, scientists must have the management experience to run a remote team of researchers, and may need the financial backing to launch a company on their own. Aspirants should also be prepared for quick turnover with regard to projects and jobs: virtual start-ups are often designed to sell off individual projects — or the full company — to larger firms...."
*Coexpression of CPR from Various Origins Enhances Biotransformation Activity of Human CYPs in S. bombe*
by Ina Neunzig, Maria Widjaja, Frank T. Peters, Hans H. Maurer, Alain Hehn, Frédéric Bourgaud, Matthias Bureik
"Cytochrome P450 enzymes (CYPs or P450s) are the most important enzymes involved in the phase I metabolism of drugs (and other xenobiotics) in humans, and the corresponding drug metabolites are needed as reference substances for their structural confirmation and for pharmacological or toxicological characterization. We have previously shown that biotechnological synthesis of such metabolites is feasible by whole-cell biotransformation with human CYPs recombinantly expressed in the fission yeast Schizosaccharomyces pombe. It was the aim of this study to compare the activity of seven human microsomal CYPs (CYP2C9, CYP2D6, CYP3A4, CYP3A5, CYP3A7, CYP17, and CYP21) upon coexpression with NADPH-cytochrome P450 oxidoreductases (CPRs) from various origins, namely, human CPR (hCPR) and its homologues from fission yeast (ccr1) and the bishop’s weed Ammi majus (AmCPR), respectively. For this purpose, 28 recombinant strains were needed, with five of them having been constructed previously and 23 strains being newly constructed. Bioconversion experiments showed that coexpression of a CPR does not only influence the reaction rate but, in some cases, also exerts an influence on the metabolite pattern. For CYP3A enzymes, coexpression of hCPR yielded the best results, while for another two, hCPR was equally helpful as ccr1 (both CYP17 and CYP21) or AmCPR (CYP17 only), respectively. Interestingly, CYP2D6 displayed its highest activity when coexpressed with ccr1 and CYP2C9 with AmCPR. These results corroborate the view of CPR as a well-suited bio-brick in synthetic biology for the construction of artificial enzyme complexes."
"Published in the Proceedings of the National Academy of Sciences (PNAS), the papers are both based on the manipulation of the same material—an atomic-scale defect in diamond known as the nitrogen vacancy center.
Both works also leverage the intrinsic “spin” of this defect for the applications in temperature measurement and information processing. This spintronics approach involves understanding and manipulating the spin of electronics for technological advancement.“These studies build on research efforts undertaken over the last 20 years to isolate and control single electronic spins in the solid state,” says David Awschalom, a principle investigator on both papers and a molecular engineering professor at the University of Chicago. “Much of the initial motivation for working in this field was driven by the desire to make new computing technologies based on the principles of quantum physics.“In recent years the research focus has broadened as we’ve come to appreciate that these same principles could enable a new generation of nanoscale sensors.” Control qubits with lightIn the first PNAS paper, Awschalom and six co-authors at the University of California, Santa Barbara and the University of Konstanz describe a technique that offers new routes toward the eventual creation of quantum computers, which would possess far more capability than modern classical computers.In this application, Awschalom’s team has developed protocols to fully control the quantum state of the defect with light instead of electronics.The quantum state of interest in this defect is its electronic spin, which acts as quantum bit, or qubit, the basic unit of a quantum computer.In classical computers, bits of information exist in one of only two states: zero or one. In the quantum mechanical realm, objects can exist in multiple states at once, enabling more complex processing.This all-optical scheme for controlling qubits in semiconductors “obviates the need to have microwave circuits or electronic networks,” Awschalom says. “Instead, everything can be done solely with photons, with light.”As a fully optical method, it shows promise as a more scalable approach to qubit control. In addition, this scheme is more versatile than conventional methods and could be used to explore quantum systems in a broad range of materials that might otherwise be difficult to develop as quantum devices.Single spin thermometersResearchers describe the quantum thermometer application in a second PNAS paper. The technology represents a new direction for the manipulation of quantum states, which is more commonly linked to computing, communications, and encryption.In recent years, defect spins had also emerged as promising candidates for nanoscale sensing of magnetic and electric fields at room temperature. With thermometry now added to the list, Awschalom foresees the possibility of developing a multifunctional probe based on quantum physics."
PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
Gerd Moe-Behrens's insight:
by Takahashi MK, Lucks JB.
"Antisense RNA transcription attenuators are a key component of the synthetic biology toolbox, with their ability to serve as building blocks for both signal integration logic circuits and transcriptional cascades. However, a central challenge to building more sophisticated RNA genetic circuitry is creating larger families of orthogonal attenuators that function independently of each other. Here, we overcome this challenge by developing a modular strategy to create chimeric fusions between the engineered transcriptional attenuator from plasmid pT181 and natural antisense RNA translational regulators. Using in vivo gene expression assays in Escherichia coli, we demonstrate our ability to create chimeric attenuators by fusing sequences from five different translational regulators. Mutagenesis of these functional attenuators allowed us to create a total of 11 new chimeric attenutaors. A comprehensive orthogonality test of these culminated in a 7 × 7 matrix of mutually orthogonal regulators. A comparison between all chimeras tested led to design principles that will facilitate further engineering of orthogonal RNA transcription regulators, and may help elucidate general principles of non-coding RNA regulation. We anticipate that our strategy will accelerate the development of even larger families of orthogonal RNA transcription regulators, and thus create breakthroughs in our ability to construct increasingly sophisticated RNA genetic circuitry."
by +David Bikard Wenyan Jiang, Poulami Samai, Ann Hochschild, Feng Zhang and Luciano A. Marraffini
"The ability to artificially control transcription is essential both to the study of gene function and to the construction of synthetic gene networks with desired properties. Cas9 is an RNA-guided double-stranded DNA nuclease that participates in the CRISPR-Cas immune defense against prokaryotic viruses. We describe the use of a Cas9 nuclease mutant that retains DNA-binding activity and can be engineered as a programmable transcription repressor by preventing the binding of the RNA polymerase (RNAP) to promoter sequences or as a transcription terminator by blocking the running RNAP. In addition, a fusion between the omega subunit of the RNAP and a Cas9 nuclease mutant directed to bind upstream promoter regions can achieve programmable transcription activation. The simple and efficient modulation of gene expression achieved by this technology is a useful asset for the study of gene networks and for the development of synthetic biology and biotechnological applications.>>"
*Supreme Court Decision Opens the Doors to A Boom in Synthetic Biology*
by Morgan Clendaniel
"Today’s Supreme Court ruling on the patenting of human genes was a boost to the field of synthetic biology. While human genes cannot be directly patented, the Court found, so-called complementary DNA can. This is DNA that is synthesized from the rNA in a genetic template and then cloned. The Court found that while naturally occurring DNA is not a human creation, "the lab technician unquestionably creates something new when cDNA is made. "
Synthetic biology relies on this synthesized cDNA. Synthetic biology has been in the news lately for many reasons. Last Friday a unique Kickstarter campaign closed with almost $500,000 in donations (well over a $65,000 goal). As a result, three young DIY bio enthusiasts will distribute to almost 6,000 backers, who kicked in at least $40 each, packages of synthetically genetically engineered seeds that supposedly will allow each of them to grow bioluminescent house plants--Arabidopsis and eventually roses--at home. Synthetic biology is an emerging and controversial scientific field that uses gene-writing software to compile DNA sequences, in this case, taken and modified from a firefly, that are then printed onto a blotter. The Glowing Plants project will use a "Gene Gun" to "fire" particles of gold coated in DNA into living cells. The use of the gun does an end run around USDA regulations that govern the use of viruses or other pathogens to modify DNA. The project started at Singularity University. It’s designed as a public demonstration of the power of DIY Biology. And herein lies the problem for some critics. The potential applications of synthetic biology are to create immensely useful, lifesaving things, like a cure for Alzheimer’s disease, or a rice crop that needs as little water as a cactus, or an algae or other single-celled species that can produce near-perfect petroleum analogues from the sun or from toxic chemicals. These glowing plants don’t do any of that, and scientists and environmentalists question if the wow factor is really worth the risk. Though the project is technically legal, its sheer hubris has kickstarted some serious from scientists and environmental groups that object to the release of these seeds to the public, with the chance that the DNA will get into the natural gene pool with unknown consequences. An anti-synthetic bio group called ETC has started a fundraising drive of their own, dubbed a "Kickstopper." "To date all [experts] have agreed that no synthetic organisms should yet be released into the environment without 'precaution,' 'prudent vigilance,' regulation, monitoring and other sober and sensible safeguards. Yet now the US government appears ready to avert its eyes," they write on their website. And a on Avaaz.org has over 13,000 signatures. Other scientists object that it’s unlikely that the small plant will actually be able to process enough energy to visibly glow, even slightly or for a few seconds at a time. The journal Nature notes that the Glowing Plants project is among other genetically modified, glow in the dark creature to be available to the public soon. A company called BioGlow in St. Louis also intends to sell glowing houseplants. Commercially available synthetically engineered animals, to say nothing of human cDNA, are still far away, but if they appear, they’ll be protected by intellectual property law."
"For millennia, people have gone out of their way to change the biological world around them. We’ve killed threatening species, domesticated others, and manipulated the habitats of still others to make food production and basic survival an easier undertaking. So the notion that our tinkering with nature is a fundamental departure from a past Eden in which we were “a part of nature” is a false dichotomy: every action we take – and some have been more intentional than others – contributes to a changing world.
The potential magnitude of our intervention, however, is greater today than ever before. Before the advent of molecular biology, the complexity of living systems kept the underlying mechanisms of our tinkering obscure. We may engage in selective breeding (a crude form of biological engineering) to produce a more productive crop or a cuter dog, but our metric of selection – size of an ear of corn, or furriness – is the end result of millions of intricate biological interactions. Following the great reductionist tradition of experimental science, we’ve traced biological function to the genetic level and are now looking for codified ways of enacting discrete interventions in predictable ways. This is synthetic biology: a young field promising great things. Kevin Munnelly is the President and CEO of Gen9, a company founded by some of the biggest names in synthetic biology research to commercialize a better way of synthesizing DNA. In a recent article published in the journal ACS Synthetic Biology, Munnelly outlines the transformative potential of the field and identifies a key obstacle standing in its way: standardization. As experimental techniques have advanced, individual researchers have jumped right in, designing new genes or regulatory elements, seeing how they affect a microbe, and publishing the results. Another scientist may have accomplished the same feat in a different way, leading future investigators unclear on which method is most desirable. If there were a trusted repository of DNA sequences vetted to produce certain results to spec, it would save a lot of time and minimize the number of variables in a given experiment. Standardization of parts is not a particularly glamorous field of work, but, leading synthetic biologists, agree, it’s essential. Imagine trying to construct a Boeing Dreamliner from a heap of metal and wires. Standard parts get everyone on the same 8.5”x11” page. Fortunately, the global community of synthetic biology coppersmiths is already building a stockroom. The Registry for Standard Biology Parts is up to more than 7000 components. “These are all annotated and confirmed gene sequences,” explains Munnelly, “vetted through peer review publications or public companies that provide validation.” Things like gene promoters, protein coding domains, termination sequences, plasmids, vector sequences, or genes for specific functions...."
"What is the origin of life on Earth? What is the future of life in the age of synthetic biology? These are two of the biggest questions of contemporary biology, and the questions that drive Adam Rutherford’s new book, Creation: How Science is Reinventing Life Itself, a compelling and accessible two-part look through the history and future of living cells. Through chapters that span the early history of microscopy to recent debates on the regulation of biotechnology and genomics, Rutherford tells the complicated story of the science of life as it might have been and as it might be. These two difficult questions, of origins and offspring, have been tightly linked in the life sciences for over a century. In the work of engineer-biologists like Jacques Loeb–who at the beginning of the 20th century sought to create “artificial life” through manipulation of sea urchin eggs–engineering was a tool for experimentation to better understand biology. For Loeb, engineering could be used to examine the validity of biological theory: “the proof of the explicability of any single life phenomenon is furnished as soon at it is successfully controlled unequivocally through physical or chemical means or is repeated in all details with nonliving materials.” Echoes of this sentiment are found everywhere in synthetic biology today, where Richard Feynman’s much more quotable remark is frequently invoked: “What I cannot create, I do not understand.”..."
*Bacteria are single celled organisms that can do amazing things in multicellular groups, with complex coordinated behaviors emerging from the interaction of genetic networks, chemical environments, and the physics of cell growth. Last year I wrote about the work of Tim Rudge and Fernan Federici and their incredible images of bacterial growth patterns. Their paper, with colleagues from the Haseloff Lab at the University of Cambridge, was recently published in ACS Synthetic Biology, showing how complex fractal patterns in colonies of E. coli emerge simply from the physical interactions of rod shaped cells. In this experiment, E. coli cells are labelled with two colors of fluorescent protein (they are otherwise genetically identical) and seeded at low density onto a surface. As they grow and divide, the rod shaped cells begin to bump into each other, creating jagged boundaries between the two fluorescent populations. These jagged lines are fractal, self-similar at many scales. Using their CellModeller program, the team found that they could accurately model this fractal behavior by including only physical parameters like viscous drag, cell shape, and growth rate, rather than biological properties like cell-cell communication or chemotaxis. Indeed, when they used E. coli mutants that were spherical instead of rod-shaped, the fractal pattern disappeared..."
"Constructing polycistronic operons is an advantageous strategy for coordinating the expression of multiple genes in a prokaryotic host. Unfortunately, a basic construct consisting of an inducible promoter and genes cloned in series does not generally lead to optimal results. Here, a combinatorial approach for tuning relative gene expression in operons is presented. The method constructs libraries of post-transcriptional regulatory elements that can be cloned into the noncoding sequence between genes. Libraries can be screened to identify sequences that optimize expression of metabolic pathways, multisubunit proteins, or other situations where precise stoichiometric ratios of proteins are desired."
byTarl W. Prow, Daniel Sundh, Gerard A. Lutty "Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in diverse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS...."http://bit.ly/15U7uqE
"It is a paradox that bedevils genomic medicine: despite near-universal agreement that doctors and geneticists should exchange more data, there has been scant movement towards achieving this goal.
Now, a consortium of 69 institutions in 13 countries hopes to address the problem by creating an organization to enable the free flow of information in genomic medicine. On 5 June, the consortium, which is calling itself the ‘global alliance’, announced that the organization will develop standards and policies to encourage data-sharing of a person’s DNA sequence combined with clinical information. The alliance’s founders are basing their model on the World Wide Web Consortium, which in the 1990s established standards for the programming language HTML and spurred the growth of web pages across the Internet....."
Figure: Children making DNA ladders out of plasticine as part of a Science, Art and Writing (SAW) project on the theme of synthetic biology.
*Building foundations for an open perspective on synthetic biology research and innovation*
by Jenni Rant, Joyce Tait
"Most present day scientists are extremely specialized in their respective fields and hard-wired into a peer review system that forms an integral part of research. Regulations to limit negative impacts of their research together with guidelines to ensure that research is carried out ethically are pervasive. Scientists collaborate on projects that bring complementary expertise together and are well equipped to share factual, accurate and relevant accounts of their research within the scientific community. The global communication network, increasingly driven by social media, enables the latest findings in research to be shared at an almost synaptic speed with recipients who perceive this knowledge in diverse ways. One could assume that the translation of research into a language accessible to a broad audience would be easy, contributing to maintaining informed public assessment of research and innovation, and also encouraging a more general interest in science as part of society. However, the reality has been patchy communication that is often reactive, triggered by recent developments and potential negative publicity rather than carefully considered proactive engagement. The recent measles outbreak serves as a powerful example of how messages from a single scientific paper published in 1998 caused a ripple effect leading to public concern, reduced uptake of vaccination and a general mistrust of scientists and government organizations. The paper has since been retracted (Wakefield et al., 1998; The Editors of The Lancet, 2010) but the implications demonstrate how society processes, disseminates and reacts to information. When a new area of scientific advancement emerges from basic research, communication in a wide variety of forms will be key to framing that technology in the minds of members of the public, affecting market potential and the regulatory systems derived through the political process. Restrictions imposed by the UK government in 2004 for the cultivation of a herbicide-resistant maize variety were deemed too unfavourable for economic viability even after Farm Scale Evaluation trials showed that it caused less damage to wildlife than conventional varieties (Mason, 2004). In Europe discussions on the future governance of new technologies such as synthetic biology frequently refer to the genetic modification (GM) crop experience, where negative public framing of GM technology, driven by a pressure group campaign with uncritical media support, has proven very resistant to change, despite strong and consistent evidence of the benefits of GM crops and their relative safety compared to the pesticides they replace. The prospect of another polarized public debate of the type that has surrounded GM crops had already convinced policy-makers and scientists to pay early attention to public dialogue on synthetic biology (Bhattachary et al., 2010). Communication processes that are balanced and evidence-based will be increasingly important in the framing of new technologies or the re-framing of existing ones...."
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