by Ratushny AV, Saleem RA, Sitko K, Ramsey SA, Aitchison JD. Source 1] Institute for Systems Biology, Seattle, WA, USA  Seattle Biomedical Research Institute, Seattle, WA, USA. Abstract Positive feedback is a common mechanism enabling biological systems to respond to stimuli in a switch-like manner. Such systems are often characterized by the requisite formation of a heterodimer where only one of the pair is subject to feedback. This ASymmetric Self-UpREgulation (ASSURE) motif is central to many biological systems, including cholesterol homeostasis (LXRα/RXRα), adipocyte differentiation (PPARγ/RXRα), development and differentiation (RAR/RXR), myogenesis (MyoD/E12) and cellular antiviral defense (IRF3/IRF7). To understand why this motif is so prevalent, we examined its properties in an evolutionarily conserved transcriptional regulatory network in yeast (Oaf1p/Pip2p). We demonstrate that the asymmetry in positive feedback confers a competitive advantage and allows the system to robustly increase its responsiveness while precisely tuning the response to a consistent level in the presence of varying stimuli. This study reveals evolutionary advantages for the ASSURE motif, and mechanisms for control, that are relevant to pharmacologic intervention and synthetic biology applications.
"GenomeSpace is a software environment that seamlessly connects genomic analysis tools. GenomeSpace is available at: www.genomespace.org
Researchers from the Broad Institute of MIT and Harvard have announced that GenomeSpace, a software environment that seamlessly connects genomic analysis tools, is now available to the scientific community. During her keynote address at Bio-IT World Conference and Expo on Tuesday, Jill Mesirov, director of computational biology and bioinformatics at the Broad Institute, invited biomedical researchers and tool developers to explore this beta release of the new resource and to use it in their work.
Currently, in order to make use of multiple analysis tools and data sources, biologists need to convert between the different data formats they use. This often involves error-prone spreadsheet manipulations or requires programming skills to write scripts. Mesirov’s team and her collaborators set out to change that.
“Our goal is to bring the ever-changing wealth of genomic analysis methods and whatever data are required to the fingertips of any biologist,” said Mesirov.
The GenomeSpace environment currently connects six tools: GenePattern, Galaxy, Integrative Genomics Viewer (IGV), Cytoscape, Genomica, and the UCSC Genome Browser. Many projects in genomic research rely on one or more of these tools. For instance, if researchers want to test a hypothesis about genetic differences between two stages of breast cancer, they might first use an analytical tool such as GenePattern to detect genes of interest; then IGV to view their genetic sequence; and then Cytoscape to see protein-protein interactions. GenomeSpace allows them to seamlessly transition between all of these tools to carry a project through to completion...."
"We seek to construct physical and mathematical models of life. Such models allow us to test our understanding of how living systems function and how they respond to human imposed stimuli. One system is a genomically and chemically complete model of a minimal cell. This cell is a hypothetical bacterium with the fewest number of genes possible. Such a minimal cell provides a platform to ask about the essential features of a living cell and forms a platform to investigate "synthetic biology." A second system is "Body-on-a-Chip" which is a microfabricated microfluidic system with cells or tissue constructs representing various organs in the body. It can be constructed from human or animal cells and used in drug discovery development. That model is a physical representation of a physiologically based pharmacokinetic model. Both the computer and the physical models provide insight into the underlying biology and provide new tools to make use of that understanding to provide benefits to society."
"Synthetic biology is playing a key role in creating new tools for rapid detection of potentially fatal bacterial infections such as E. coli and allowing scientists to create novel molecules that may provide new antibiotics to tackle the problems of multiply-resistant strains.
Prof Chris Thomas and Dr Tim Dafforn from the University of Birmingham are part of a growing number of scientists worldwide searching for effective ways to deal with increasingly problematic superbugs. A critical stage in dealing with infection is identifying what the bacterium is that is causing the problem.
Tim Dafforn is an expert on biophysical spectroscopy and, more specifically, a spectroscopic technique that detects molecules when they line up in solution if you stir it – just like when you stir a bowl of spaghetti...."
"This article uses data from Thomson Reuters Web of Science to map and analyse the scientific landscape for synthetic biology. The article draws on recent advances in data visualisation and analytics with the aim of informing upcoming international policy debates on the governance of synthetic biology by the Subsidiary Body on Scientific, Technical and Technological Advice (SBSTTA) of the United Nations Convention on Biological Diversity. We use mapping techniques to identify how synthetic biology can best be understood and the range of institutions, researchers and funding agencies involved. Debates under the Convention are likely to focus on a possible moratorium on the field release of synthetic organisms, cells or genomes. Based on the empirical evidence we propose that guidance could be provided to funding agencies to respect the letter and spirit of the Convention on Biological Diversity in making research investments. Building on the recommendations of the United States Presidential Commission for the Study of Bioethical Issues we demonstrate that it is possible to promote independent and transparent monitoring of developments in synthetic biology using modern information tools. In particular, public and policy understanding and engagement with synthetic biology can be enhanced through the use of online interactive tools. As a step forward in this process we make existing data on the scientific literature on synthetic biology available in an online interactive workbook so that researchers, policy makers and civil society can explore the data and draw conclusions for themselves."
Lehman N. "When RNA is replicated in cell-free systems, a ubiquitous problem is the hijacking of the system by short parasitic RNA sequences. In this issue of Chemistry & Biology, Bansho et al. show that compartmentalization into water-in-oil droplets can ameliorate this problem, but only if the droplets are small. This result helps to both recapitulate abiogenesis and optimize synthetic biology." http://1.usa.gov/Ici5En
" A lot of people were skeptical when two young California-based researchers set out more than a decade ago to create a completely human-derived alternative to the synthetic blood vessels commonly used in dialysis patients. Since then, they've done that and more. "There were a lot of doubts in the field that you could make a blood vessel, which is something that needs to resist pressure constantly, 24-7, without any synthetic materials in it," explains Nicolas L'Heureux, a co-founder and the chief scientific officer of Cytograft Tissue Engineering Inc. "They didn't think that was possible at all." But they were wrong." http://bit.ly/JlZlPa
Athena r4 – Modular CAD/CAM software for Synthetic Biology
"Athena is a software that allows biological models to be constructed as modules. Modules can be connected to one another without altering the modules themselves. In addition, Athena houses various tools useful for designing synthetic networks including tools to perform simulations, automatically derive transcription rate expressions, and view and edit synthetic DNA sequences. New tools can be incorporated into Athena without modifying existing program via a plugin interface, IronPython scripts, Systems Biology Workbench interfacing and the R statistical language.
Philipp Holliger - Synthetic biology of nucleic acid replication
"A critical event in the origin of life is thought to be the emergence of a molecule capable of self-replication as well as mutation, and hence evolution towards more efficient replication. We have built a powerful in vitro system for directed evolution, called compartmentalized self-replication (CSR), which mimics this process in the laboratory. Our current focus is the application of the CSR technology to the evolution of novel polymerases with an expanded substrate spectrum. Polymerases capable of replicating non-canonical nucleic acid substrates have applications ranging from the recovery of ancient DNA sequences from archaeological and palaeontological specimens to ultra-bright DNA probes for molecular genetics....." http://bit.ly/I2FQ2q
"Last summer, biologist Andrew Kasarskis was eager to help decipher the genetic origin of the Escherichia coli strain that infected roughly 4,000 people in Germany between May and July. But he knew it that might take days for the lawyers at his company — Pacific Biosciences of Menlo Park, California — to parse the agreements governing how his team could use data collected on the strain. Luckily, one team had released its data under a Creative Commons licence that allowed free use of the data, allowing Kasarskis and his colleagues to join the international research effort and publish their work1 without wasting time on legal wrangling.
Together with other funders, the Ewing Marion Kauffman Foundation, based in Kansas City, Missouri, is now launching a product that aims to “create the world’s largest pool of openly available, user-contributed data about health and genomics” in hopes of easing challenges with informed consent and data ownership that some biomedical researchers say are holding science back in the era of ‘big data’. The Portable Legal Consent for Common Genomics Research, developed by the Consent to Research project, is a system through which users can donate their data to databases that remove identifying details, such as name and e-mail address. The databases then assign an identification number to all of the data from each user and deliver the de-identified data to researchers, who must agree to broad conditions designed to prevent harm to the data contributors. Data donors must also undergo a detailed informed consent process, including, for instance, watching a six-and-a-half minute video that cannot be fast-forwarded...."
Podcast: What do speakers, skin and skirts have in common? Professor Paul Freemont from Imperial College London explains how bacterial cellulose is being exploited by industry and how the engineering approach of synthetic biology can help maximise its use.
Science Online New York (SoNYC) encourages audience participation in the discussion of how science is carried out and communicated online.
I found especially two citations interesting "I am an open notebook scientist, which simply means that I share all of my research online in an open format in real-time." and "Unfortunately most of that data doesn’t make it to publication. On top of that many researchers have small side projects that may never get published nor will the data that is acquired from those projects. And that doesn’t include failed experiments." Both direct dynamic publishing and unblushing of negative data have the potential to speed up the discovery process. One get quick access to new data and can rapid discuss them in a social context. An immediate feed back from the community is possible, which could help to increase the quality of the experiments, get ideas for follow ups, and make potentially collaborators interested. Negative data might help to circumvent unnecessary experiments.
Synthetic Biology of secondary metabolite biosynthesis in actinomycetes: Engineering precursor supply as a way to optimize antibiotic production
by Wolfgang Wohlleben, , Yvonne Mast, Günther Muth, Marlene Röttgen, Evi Stegmann, Tilmann Weber "Actinomycetes are a rich source for the synthesis of medically and technically useful natural products. The genes encoding the enzymes for their biosynthesis are normally organized in gene clusters, which include also the information for resistance (in the case of antibacterial compounds), regulation, and transport. This facilitates the manipulation of such pathways by molecular genetic techniques. Recent advances in DNA sequencing and analytical chemistry revealed, that not only new strains isolated from yet unexplored habitats, but also already known strains possess a large potential for the synthesis of novel compounds. Synthetic Biology now offers a new perspective to exploit this potential further by generating novel pathways, and thereby novel products, by combining different biosynthetic steps originating from different bacteria.
The supply of precursors, which are subsequently incorporated into the final product, is often already organized in a modular manner in nature and may directly be exploited for Synthetic Biology. Here we report examples for the synthesis of building blocks and possibilities to modify and optimize antibiotic biosynthesis, exemplary for the synthesis of the manipulation of the synthesis of the glycopeptide antibiotic balhimycin." http://bit.ly/Iyq0L2
"Christina Agapakis is a synthetic biologist and postdoctoral research fellow at UCLA who blogs about about biology, engineering, biological engineering, and biologically inspired engineering at Oscillator. When you factor in the fertilizer needed to grow animal feed and the sheer volume of methane expelled by cows (mostly, though not entirely, from their mouths), a carnivore driving a Prius can contribute more to global warming than a vegan in a Hummer. Given the environmental toll of factory farming it’s easy to see why people get excited about the idea of meat grown in a lab, without fertilizer, feed corn, or burps. In this vision of the future, our steaks are grown in vats rather than in cows, with layers of cow cells nurtured on complex machinery to create a cruelty-free, sustainable meat alternative. The technology involved is today used mainly to grow cells for pharmaceutical development, but that hasn’t stopped several groups from experimenting with “in vitro meat,” as it’s called, over the last decade. In fact, a team of tissue engineers led by professor Mark Post at Maastricht University in the Netherlands recently announced their goal to make the world’s first in vitro hamburger by October 2012. The price tag is expected to be €250,000 (over $330,000), but we’re assured that as the technology scales up to industrial levels over the next ten years, the cost will scale down to mass-market prices...."
"Open access (OA) scholarly publishing is a contentious subject. The loudest, most-readily heard voices are often those from the extreme ends of the spectrum, those lost in unrealistic idealism or those mired in the mundane details of running a business. Pairing these extremes leads to interesting, but ultimately unproductive conversations.
Instead, we might turn our attention away from the shouting, and focus on those somewhere in the middle, a group more interested in finding real-world, pragmatic solutions to translate idealism into functional publishing models. Cameron Neylon has, for several years now, been one of the most thoughtful and thorough proponents of OA and opening science in general...."
The Bold Future of Alternative Energy Jay Keasling May 8 University of Nebraska-Lincoln
by IANR News Service
"A native Nebraskan is working to develop cost-effective biofuels to replace gasoline, diesel and jet fuels with a clean, renewable alternative.
......He is chief executive officer of the Joint BioEnergy Institute in Emeryville, Calif. The institute is one of three Bioenergy Research Centers funded by the U.S. Department of Energy to advance the next generation of biofuels.
A leader in the field of synthetic biology, Keasling and colleagues at JBEI have engineered a strain of Escherichia coli bacteria to produce biodiesel fuel from biomass such as switchgrass, without the need of enzyme additives.
His team currently is working to increase the efficiency and speed by which its engineered E. coli strain can be cost-effective and economically competitive in quantities needed to meet the world need.
"With today's concerns about how petroleum-based fuels are affecting the global climate, and how increasing costs and dependence on foreign sources of petroleum-based fuels affect countries, fuels that are renewable and sustainable are vital," said Ronnie Green, Institute of Agriculture and Natural Resources Harlan vice chancellor at UNL and moderator of the Heuermann Lectures.
"We are tremendously fortunate to have this leader in the field discuss alternative energy as we end our first year of Heuermann Lectures," Green added.
Synthetic biology tools
A story in Discover magazine once said "Keasling spent his childhood immersed in the practical end of biology, chemistry, and engineering – he was raised on a farm" near Harvard, Neb.
It was work to save lives of malaria sufferers that provided him the insight into the work he now does with biofuels. Up to a million people, many of them children, die of malaria a year.
Using synthetic biology tools to produce a microbial-based version of the most powerful anti-malarial drug artemisinin at a price affordable to the poor, he saw ways the same synthetic biology techniques would apply to producing carbon-neutral transportation fuels from plant biomass......"
BY DREW ENDY "BIOLOGISTS HAVE BECOME ENGINEERS OF THE LIVING WORLD. BY MAKING THEIR BIOENGINEERED SOLUTIONS TO GLOBAL PROBLEMS OPENLY AVAILABLE, WE CAN TRANSFORM THE DEVELOPING WORLD Can the reengineering of biology be coupled to the spread of tools and knowledge sufficient to improve the health of people and the environment worldwide? We believe the answer is yes, albeit with much work to be accomplished both technically and culturally. Practically, a comprehensive overhaul of the process by which living systems are engineered is needed. Legal, political, and cultural innovations are also required to collectively insure that the resulting knowledge and tools are freely availably to those who would use them constructively.
We do not know how to make biology easy to engineer (think playing with Legos or coding software with Java). However, technical inventions prototyped over the past six years point the way to a future in which biology is much easier to engineer relative to today. For example, in the summer of 2009, a team of undergraduates at the University of Cambridge won the International Genetically Engineered Machines (iGEM) competition by engineering seven strains of E. coli, each capable of synthesizing a different pigment visible to the naked eye. The resulting set, collectively known as E. chromi, required rerouting the metabolism of the bacteria so that natural precursor chemicals are converted across a palette of seven colors, from red to purple; such genetic color generators can be used to program microbes to change color in response to otherwise invisible environmental pollutants or health conditions. A few years ago such a project would have required several PhD-level experts in biology and metabolic engineering and would have likely taken a few years. Today, undergraduates can perform such work in months. This change in reality is due to two advances—tools and sharing—both of which are ready for their own revolutions...." http://bit.ly/gKBVUt
"Genomes are complicated. Even the concept of a “gene” isn’t as straightforward as you might expect. Genes are the units of heredity, the bits of DNA and RNA that do something inside a cell. But DNA doesn’t do much of anything by itself; genes need proteins to copy themselves and to turn the small percentage of DNA that codes for a protein into enzymes. Functional parts of DNA can code for proteins or tell the cellular machinery where to start copying the chromosomes, where to start and stop the transcription of DNA into RNA and the translation of RNA into protein. In the genomes of even the simplest cells, these different components are jumbled together, overlapping with each other backwards and forwards in a dense and highly evolved sequence. While we can read DNA sequences at exponentially increasing speed and decreasing cost, understanding in detail how all these sequences are tuned to control when and where and in what conditions specific proteins are expressed is still often plodding along one PhD thesis at a time.
A paper published last week in the Proceedings of the National Academy of Science by Karsten Temme, Dehua Zhao, and Chris Voigt uses our increasing ability to synthesize DNA to tackle the problem from a very different angle. Instead of picking apart a complex set of genes to understand the regulatory details, the sequence was entirely redesigned to strip out complexity and to create a more understandable, computer-readable version of the genes. The authors started with the 23,500 base pair, 20-gene cluster that the bacteria Klebsiella oxytoca uses to fix nitrogen and “refactored” it, rewriting the sequence so that the expression of each protein-coding gene was controlled by a synthetic regulator. Refactoring is: “a term borrowed from software development whereby the code underlying a program is rewritten to achieve some goal (e.g., stability) without changing functionality.” Refactoring the nitrogen fixation gene cluster to make its regulation easier to understand and engineer involved replacing every start and stop sequence (promoter, ribosome binding site, and terminator) with synthetic versions, clustering co-regulated genes together, removing non-coding regions, and re-encoding the protein coding sequence to “create a DNA sequence as divergent as possible from the wild-type gene” and remove potential internal regulation sites......"
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