Researchers who hope to use stem cells—the unspecialized cells that produce all of our tissues—to treat diseases face a dilemma. Stem cells from embryos (ES cells) could provide a wealth of new cells but spark ethical objections. Stem cells produced from adult cells (so-called induced pluripotent stem [iPS] cells) avoid the ethical difficulties, but some scientists have questioned whether they are as powerful as ES cells. A new study suggests that the two types of stem cells are equivalent and may help soothe worries about the capabilities of iPS cells.
“I think it was a very well done study, and it will ease some of the concerns about ES cells versus iPS cells,” says stem cell biologist Joseph Wu of the Stanford University School of Medicine in Palo Alto, California, who wasn’t connected to the study. Stem cell biologist William Lowry of the University of California, Los Angeles, agrees. “It’s probably going to be a lot easier to go forward with iPS cells because of studies like this.”
ES cells can specialize into any type of cell in the body, but they are controversial because obtaining them destroys embryos. In 2006, researchers found a possible workaround. Adding four genes to a specialized adult cell—such as a skin cell from a patient—can convert it into an iPS cell. These cells seem to have similar abilities as ES cells in the lab, and iPS cells don’t rouse the ethical objections of ES cells. Such reprogrammed cells are now widely used by stem cell labs around the world, and the scientist who figured out how to make them, Shinya Yamanaka of Kyoto University in Japan, won the Nobel Prize in Physiology or Medicine in 2012 for the discovery.
Canadian designer Julie Legault has developed a desktop biolab to make synthetic biology more accessible, allowing users to hack DNA at home and monitor ...
Cells are complex machines capable of processing information by means of an entangled network of molecular interactions. A crucial component of these decision-making systems is the presence of memory and this is also a specially relevant target of engineered synthetic systems. A classic example of memory devices is a 1-bit memory element known as the flip-flop. Such system can be in principle designed using a single-cell implementation, but a direct mapping between standard circuit design and a living circuit can be cumbersome. Here we present a novel computational implementation of a 1-bit memory device using a reliable multicellular design able to behave as a set-reset flip-flop that could be implemented in yeast cells. The dynamics of the proposed synthetic circuit is investigated with a mathematical model using biologically-meaningful parameters. The circuit is shown to behave as a flip-flop in a wide range of parameter values. The repression strength for the NOT logics is shown to be crucial to obtain a good flip-flop signal. Our model also shows that the circuit can be externally tuned to achieve different memory states and dynamics, such as persistent and transient memory. We have characterized the parameter domains for robust memory storage and retrieval as well as the corresponding time response dynamics.
Bacteria adjust to different environmental conditions mainly by modulating transcription. Internal and external stimuli affect regulatory elements, all of which formulate the complex transcriptional profile of an organism at any given moment. In synthetic biology, the use of synthetic genetic circuits and metabolic pathways, which are often unresponsive to the aforementioned native regulation, is a common procedure. Such behavior can be advantageous, as it allows the organism to remain unaffected by unpredictable perturbations. In many cases, however, the lack of interaction with the internal control leads to undesired effects: metabolic intermediate accumulation, reduced fitness, and decreased product yields. This sets the framework of a recent research paper from the groups of Stephen Mayo and Richard Murray, where they describe a de novo transcription factor that is regulated by vanillin.
Vanillin is a byproduct of lignin degradation and an important substrate for the flavor industry. It is a phenolic compound with cytotoxic effects. In this article, the researchers modified qacR, a tetR-family repressor to bind vanillin, which binds to DNA via a helix-turn-helix domain. In the absence of the effector molecule, qacR physically inhibits RNA polymerase from transcribing the region downstream the binding site (see figure). The inducer causes conformational changes that prevent this binding, thus activating the gene. The procedure for qacR engineering consists of three steps:
(i) computational protein design. The researchers superimposed vanillin with the qacR crystal structure, enabling them to identify the potential binding conformations and the crucial aminoacids. They subsequently came up with a number of protein mutants that could form the correct interactions with vanillin and did not have steric clashes.
(ii) cell-free initial screening. The proteins resulting from the previous step were tested in an in vitro transcription/translation system. This methodology let the authors of the paper validate the repression qacR imposes on a reporter gene (GFP), while screening the functionality of the engineered proteins. Since all of the initial modified proteins failed to be activated by vanillin, the researchers went back to step (i) and designed more modifications. This time, two mutants showed the desired phenotype.
(iii) in vivo validation. As a last step, the two proteins from step (ii) were tested in E.coli. Both were able to suppress GFP expression in the lack of activator. One of them responded positively to increasing concentrations of vanillin, resulting in increased fluorescence.
We need to science the sh*t out of this: Synthetic Biology in Space PLoS Blogs (blog) How often is the lead character in a film a Botanist? Or more to the point, how often would that be a good thing?!
A live chat hosted by PloS Synbio blog with Dr. Fuzhong Zhang and members of his group at Washington University in St. Louis. We explore Dr. Zhang's recent ...
Systems biology, some have claimed (1), attempts the impossible and is doomed to fail. Possible definitions abound, but systems biology is widely understood to be an approach for studying the behavior of systems of interacting biological components that combines experiments with computational and mathematical reasoning. Modeling complex systems occurs throughout the sciences, so it may not be immediately clear why it should attract greater skepticism in molecular and cell biology than in other scientific disciplines. The way in which biological models are often presented and interpreted (and overinterpreted) may be partly to blame. As with experimental results, the key to successfully reporting a mathematical model is to provide an honest appraisal and representation of uncertainty in the model's predictions, parameters, and (where appropriate) in the structure of the model itself.
Multipart and modular DNA part libraries and assembly standards have become common tools in synthetic biology since the publication of the Gibson and Golden Gate assembly methods, yet no multipart modular library exists for use in bacterial systems. Building upon the existing MoClo assembly framework, we have developed a publicly available collection of modular DNA parts and enhanced MoClo protocols to enable rapid one-pot, multipart assembly, combinatorial design and expression tuning in E. coli. The Cross-disciplinary Integration of Design Automation Research lab (CIDAR) MoClo Library is openly available and contains promoters, ribosomal binding sites, coding sequence, terminators, vectors, and a set of fluorescent control plasmids. Optimized protocols reduce reaction time and cost by >80% from previously published protocols.
By Steven Burgess Hello, my name is Steven. I am a postdoc in molecular plant biology based in Cambridge, UK. I am very grateful to the PLOS blogs to have entrusted me with the role
The advancement of synthetic biology over the past decade has contributed substantially to the growing bioeconomy. A recent report by the National Academies highlighted several areas of advancement that will be needed for further expansion of industrial biotechnology, including new focuses on design, feedstocks, processing, organism development, and tools for testing and measurement; more particularly, a focus on expanded chassis and end-to-end design in an effort to move beyond the use of E. coli and S. cerivisiea to organisms better suited to fermentation and production; second, continued efforts in systems biology and high-throughput screening with a focus on more rapid techniques that will provide the needed information for moving to larger scale; and finally, work to accelerate the building of a holacratic community with collaboration and engagement between the relevant government agencies, industry, academia, and the public.
Rational pathway design is the invention of an optimally efficient route from one state (e.g. chemical structure, state of differentiation, physiological state) to another, based on knowledge of biological processes: it contrasts with the use of natural pathways that have evolved by natural selection. Synthetic biology is a hybrid discipline of biology and engineering that offers a means for rationally designed pathways to be realized in living cells. Several areas of regenerative medicine could benefit from rational pathway design, including derivation of patient-specific stem cells, directed differentiation of stem cells, replicating physiological function in an alternative cell type, construction of custom interface tissues and building fail-safe systems into transplanted tissues. Synthetic biological approaches offer the potential for construction of these, for example controllable ex vivo stem cell niches, genetic networks for direct transdifferentiation from adult fibroblast to restricted stem cell without going via induced pluripotent stem cells, signalling pathways for realizing physiological regulation in alternative cell types, morphological modules for producing self-constructing novel 'tissues' and 'kill-switches' for therapeutically applied stem cells. Given the potential of this approach, a closer convergence of the regenerative medicine and synthetic biology research fields seems timely.
Synthetic biology is on the path to becoming a US$13.4 billion market by 2019, exhibiting a sharp CAGR of 32.6% between 2013 and 2019, estimates Transparency Market Research in its latest report. The report, titled “Synthetic Biology Market – Global Industry Analysis, Size, Share, Growth, Trends and Forecast,2013 – 2019”, puts the value of the market at US$1.8 billion in 2012.Synthetic biology is a process that utilizes biology and genetic engineering to produce artificial biological systems and devices.
The process is proving to be especially pivotal in producing affordable medicines and improved nutritional products. The report zeroes in the following key factors that have shaped the growth curve of the global synthetic biology market: Increased government participation and investments being routed into scientific research as well as active initiatives taken by private players in R&D.
The information age was enabled by advances in microfabrication and communication theory that allowed information to be processed by electrons and transmitted by electromagnetic radiation. Despite immense capabilities, microelectronics has limited abilities to access and participate in the molecular-based communication that characterizes our biological world. Here, we use biological materials and methods to create components and fabricate devices to perform simple molecular communication functions based on bacterial quorum sensing (QS). Components were created by protein engineering to generate a multidomain fusion protein capable of sending a molecular QS signal, and by synthetic biology to engineer E. coli to receive and report this QS signal. The device matrix was formed using stimuli-responsive hydrogel-forming biopolymers (alginate and gelatin). Assembly of the components within the device matrix was achieved by physically entrapping the cell-based components, and covalently conjugating the protein-based components using the enzyme microbial transglutaminase. We demonstrate simple devices that can send or receive a molecular QS signal to/from the surrounding medium, and a two-component device in which one component generates the signal (i.e., issues a command) that is acted upon by the second component. These studies illustrate the broad potential of biofabrication to generate molecular communication devices.
Donwload Here http:///?book=1491904291&nejie=8grkj.html Today's synthetic biologists are in the early stages of engineering living cells to help treat diseases, ...
http://www.weforum.org/ John Heap from Imperial College London, has been hacking nature to turn waste into chemicals. Heap says we should embrace the ...
http://www.weforum.org/ "Discovery isn't the same as delivery,” says Karen Polizzi from Imperial College London. She explores how synthetic biology can scale ...
Engineered human cells that can give rise to every cell type have been induced to generate structures that resemble an embryonic kidney. This advance charts a course towards growing transplantable kidneys in culture
This is why the upcoming Investor Roundtable at SynBioBeta SF 2015 is such a valuable opportunity, because attendees get to hear from several of the major names within the current VC space.
GARTNER, an American consultancy, has a simple yet elegant way of describing the life of a promising new technology. First, it is talked up to a peak of inflated expectations. Then it falls into a trough of disillusionment. After that, if it survives, it begins climbing the slope of enlightenment. Finally, it reaches the plateau of productivity.
In the world of biotechnology CRISPR/Cas9 (see article), is still ascending towards peak expectations. True to the Gartner hype-cycle, though, an earlier star, RNA interference, or RNAi, is well and truly in the trough. The chart alongside, of Google searches for the two technologies, shows this. The question is, can RNAi climb the slope of enlightenment to become a productive and useful technology? And the answer looks increasingly likely to be “yes”.
One of the most promising applications of biosynthetic methods is to produce chemical products of high value from the ready-made chemicals. To explore the biosynthetic potentials of a chemical as a synthesis precursor, biosynthetic databases and related chemoinformatics tools are urgently needed. In the present work, a web-based tool, BioSynther, is developed to explore the biosynthetic potentials of precursor chemicals using BKM-react, Rhea, and more than 50,000 in-house RxnFinder reactions manually curated. BioSynther allows researchers to explore biosynthetic potentials, through so far known biochemical reactions, step by step interactively, which could be used as a useful tool in metabolic engineering and synthetic biology.
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