by Christina M Agapakis,Patrick M Boyle & Pamela A Silver NATURE CHEMICAL BIOLOGY | REVIEW "Metabolism is a highly interconnected web of chemical reactions that power life. Though the stoichiometry of metabolism is well understood, the multidimensional aspects of metabolic regulation in time and space remain difficult to define, model and engineer. Complex metabolic conversions can be performed by multiple species working cooperatively and exchanging metabolites via structured networks of organisms and resources. Within cells, metabolism is spatially regulated via sequestration in subcellular compartments and through the assembly of multienzyme complexes. Metabolic engineering and synthetic biology have had success in engineering metabolism in the first and second dimensions, designing linear metabolic pathways and channeling metabolic flux. More recently, engineering of the third dimension has improved output of engineered pathways through isolation and organization of multicell and multienzyme complexes. This review highlights natural and synthetic examples of three-dimensional metabolism both inter- and intracellularly, offering tools and perspectives for biological design." http://bit.ly/KoavSe
"There is one version of Craig Venter’s life story where he would’ve been a dutiful scientist at the National Institutes of Health, a respected yet anonymous researcher in genetics, perhaps. Thankfully, Venter saw that story line developing—and set about making sure it never happened.
Instead, in 1992 Venter left the NIH to head the nonprofit Institute for Genomic Research. Six years later he founded Celera Genomics, a brash rival to the NIH project that aimed to sequence the full code of the human genome. Venter had come up with a better technique—known as shotgun sequencing—to get the job done, and it changed the way we translate genetics from proteins into code. Not incidentally, it also served as a model for today’s Big Data explosion in science and research. In 2001 Celera officially “tied” the NIH to the genome finish line, though the company’s sequence was more than a bit further along. (Celera’s model genome, it just so happened, included Venter’s own DNA.)
In the decade since, Venter has been on a tear of invention and exploration. In 2004 he sailed around the world, discovering thousands of new species and sequencing millions of new genes. In 2007 he unveiled his own genome, unexpurgated (it revealed a predisposition for risk-taking, among other things). And in 2010 he announced the first successful synthesis of life—a unique critter borne from two distinct organisms, thus proving for the first time that it is indeed possible to create new organisms for specific purposes and functions. He is, in every respect, the epitome of an icon—a figure who has pushed science forward, sometimes by sheer force of will.
I spoke recently with Venter in San Francisco, at an event hosted by City Arts & Lectures and the California Academy of Sciences. What follows is an edited version of that conversation....."
RNA engineering is a quite interesting area in SynBio. The review by John C. Burnett and John J. Rossi might give some hints what kind of applications look promising in a clinical perspective:
"Recent advances of biological drugs have broadened the scope of therapeutic targets for a variety of human diseases. This holds true for dozens of RNA-based therapeutics currently under clinical investigation for diseases ranging from genetic disorders to HIV infection to various cancers. These emerging drugs, which include therapeutic ribozymes, aptamers, and small interfering RNAs (siRNAs), demonstrate the unprecedented versatility of RNA. However, RNA is inherently unstable, potentially immunogenic, and typically requires a delivery vehicle for efficient transport to the targeted cells. These issues have hindered the clinical progress of some RNA-based drugs and have contributed to mixed results in clinical testing. Nevertheless, promising results from recent clinical trials suggest that these barriers may be overcome with improved synthetic delivery carriers and chemical modifications of the RNA therapeutics. This review focuses on the clinical results of siRNA, RNA aptamer, and ribozyme therapeutics and the prospects for future successes." http://bit.ly/L4wa2W
"Biology Professor Vincent Martin describes synthetic biology as applying principles of engineering to biology — understanding how different pieces work together through modelling in order to produce a predictable result.
“If you want to build a microbe that produces an antibiotic, then you need to know what the parts or the genes are, and then how to assemble the genes together to give you what you expect you’re going to get in a reproducible, predictable way,” he explains.
Synthetic biology is generating a lot of interest, especially in Europe and the United States, perhaps owing to its almost limitless applications. Martin describes himself as “knee-deep” in synthetic biology, but says the Canadian scientific community as a whole has thus far shown only tepid interest in the new field. ...."
Hackteria is a collection of Open Source Biological Art Projects instigated in February 2009 by Andy Gracie, Marc Dusseiller and Yashas Shetty, after collaboration during the Interactivos?09 Garage Science at Medialab Prado in Madrid. The aim of the project is to develop a rich web resource for people interested in or developing projects that involve DIY bioart, open source software and electronic experimentation.
As a community platform hackteria tries to encourage the collaboration of scientists, hackers and artists to combine their experitise, write critical and theoretical reflections, share simple instructions to work with lifescience technologies and cooperate on the organization of workshops, festival and meetings.
Foundations for the design and implementation of synthetic genetic circuits
Nature Reviews Genetics by Slusarczyk AL, Lin A, Weiss R. "Synthetic gene circuits are designed to program new biological behaviour, dynamics and logic control. For all but the simplest synthetic phenotypes, this requires a structured approach to map the desired functionality to available molecular and cellular parts and processes. In other engineering disciplines, a formalized design process has greatly enhanced the scope and rate of success of projects. When engineering biological systems, a desired function must be achieved in a context that is incompletely known, is influenced by stochastic fluctuations and is capable of rich nonlinear interactions with the engineered circuitry. Here, we review progress in the provision and engineering of libraries of parts and devices, their composition into large systems and the emergence of a formal design process for synthetic biology." http://bit.ly/JeUCTy
by Jeong Wook Lee, Dokyun Na, Jong Myoung Park, Joungmin Lee Sol Choi & Sang Yup Lee "Growing concerns over limited fossil resources and associated environmental problems are motivating the development of sustainable processes for the production of chemicals, fuels and materials from renewable resources. Metabolic engineering is a key enabling technology for transforming microorganisms into efficient cell factories for these compounds. Systems metabolic engineering, which incorporates the concepts and techniques of systems biology, synthetic biology and evolutionary engineering at the systems level, offers a conceptual and technological framework to speed the creation of new metabolic enzymes and pathways or the modification of existing pathways for the optimal production of desired products. Here we discuss the general strategies of systems metabolic engineering and examples of its application and offer insights as to when and how each of the different strategies should be used. Finally, we highlight the limitations and challenges to be overcome for the systems metabolic engineering of microorganisms at more advanced levels." http://bit.ly/JVo53m Comment Metabolic engineering - Production of chemicals without petroleum " In our everyday life, we use gasoline, diesel, plastics, rubbers, and numerous chemicals that are derived from fossil oil through petrochemical refinery processes. However, this is not sustainable due to the limited nature of fossil resources. Furthermore, our world is facing problems associated with climate change and other environmental problems due to the increasing use of fossil resources. One solution to address above problems is the use of renewable non-food biomass for the production of chemicals, fuels and materials through biorefineries. Microorganisms are used as biocatalysts for converting biomass to the products of interest. However, when microorganisms are isolated from nature, their efficiencies of producing our desired chemicals and materials are rather low. Metabolic engineering is thus performed to improve cellular characteristics to desired levels. Over the last decade, much advances have been made in systems biology that allows system-wide characterization of cellular networks, both qualitatively and quantitatively, followed by whole-cell level engineering based on these findings. Furthermore, rapid advances in synthetic biology allow design and synthesis of fine controlled metabolic and gene regulatory circuits. The strategies and methods of systems biology and synthetic biology are rapidly integrated with metabolic engineering, thus resulting in "systems metabolic engineering"....." http://bit.ly/JVpsPu
This post points to one of the main challenges contemporary science is facing, the problem of big data (see Nature, SoapBox Science http://bit.ly/Jzz16M , actually an important part of what the Leukippos project is about). I did not look into the code for detail, however, the main strategy they are describing goes in the right direction. In my view provides systems theory the solution for the big data problem. We need to apply holistic thinking. On a technical side, we need a to provide the data both human and computer readable. This will allow us automated analysis, which will be readable by humans. The output data need to be structured hierarchical form the general to the detail. Eg we can structure in species, individual, organ organelle, protein, rna, dna, dna parts. Your search output will be at the highest level of abstraction, the most general group. You can than klick down to the detail. Moreover, a graphical representation of data will help to represent a huge amount of data on a small space. We will need for this a sematic web, and open and free accessible common database. This will demand open access publishing. Authors have also to deliver their data in a computer readable form. Projects like Wikidata doing some groundbreaking work for this. If I understand the app described in this paper goes in this direction described. The infrastructure, as I described it, has to be developed further in order to make this work. On a long run, I guess apps like this will be successfully. Finally, I would like to put another aspect for the solution of big data up to discussion: crowd sourcing. It has been shown in several apps like e.g. the Foldit game, that the crowd has the potential to analyze big data sets. In respect to genetic data certain ethical standards have to be meet (such as anonymity). However, this has a big potential.
Correa E, Sletta H, Ellis DI, Hoel S, Ertesvåg H, Ellingsen TE, Valla S, Goodacre R.
"Alginate is an important medical and commercial product and currently is isolated from seaweeds. Certain microorganisms also produce alginate and these polymers have the potential to replace seaweed alginates in some applications, mainly because such production will allow much better and more reproducible control of critical qualitative polymer properties. The research conducted here presents the development of a new approach to this problem by analysing a transposon insertion mutant library constructed in an alginate-producing derivative of the Pseudomonas fluorescens strain SBW25. The procedure is based on the non-destructive and reagent-free method of Fourier transform infrared (FT-IR) spectroscopy which is used to generate a complex biochemical infrared fingerprint of the medium after bacterial growth. First, we investigate the potential differences caused by the growth media fructose and glycerol on the bacterial phenotype and alginate synthesis in 193 selected P. fluorescens mutants and show that clear phenotypic differences are observed in the infrared fingerprints. In order to quantify the level of the alginate we also report the construction and interpretation of multivariate partial least squares regression models which were able to quantify alginate levels successfully with typical normalized root-mean-square error in predictions of only approximately 14 %. We have demonstrated that this high-throughput approach can be implemented in alginate screens and we believe that this FT-IR spectroscopic methodology, when combined with the most appropriate chemometrics, could easily be modified for the quantification of other valuable microbial products and play a valuable screening role for synthetic biology."
"The vascular system of a leaf provides its structure and delivers its nutrients. When you light up that vascular structure with some fluorescent dye and view it using time lapse photography, details begin to emerge that reveal nature's mathematical formula for survival. When it comes to optimizing form with function, it's tough to beat Mother Nature. With support from the National Science Foundation (NSF), Rockefeller University mathematical physicist Marcelo Magnasco and his colleague physicist Eleni Katifori analyze the architecture of leaves by finding geometric patterns that link biological structure to function. They study a specific vascular pattern of loops within loops that is found in many leaves going down to the microscopic level. Magnasco says this research is a jumping off point for understanding other systems that branch and rejoin, including everything from river systems, to neural networks and even malignant tumors."
Byung Yang Lee, Jinxing Zhang, Chris Zueger, Woo-Jae Chung, So Young Yoo, Eddie Wang, Joel Meyer, Ramamoorthy Ramesh & Seung-Wuk Lee "Piezoelectric materials can convert mechanical energy into electrical energy1, 2, and piezoelectric devices made of a variety of inorganic materials3, 4, 5 and organic polymers6 have been demonstrated. However, synthesizing such materials often requires toxic starting compounds, harsh conditions and/or complex procedures7. Previously, it was shown that hierarchically organized natural materials such as bones8, collagen fibrils9, 10 and peptide nanotubes11, 12 can display piezoelectric properties. Here, we demonstrate that the piezoelectric and liquid-crystalline properties of M13 bacteriophage (phage) can be used to generate electrical energy. Using piezoresponse force microscopy, we characterize the structure-dependent piezoelectric properties of the phage at the molecular level. We then show that self-assembled thin films of phage can exhibit piezoelectric strengths of up to 7.8 pm V−1. We also demonstrate that it is possible to modulate the dipole strength of the phage, hence tuning the piezoelectric response, by genetically engineering the major coat proteins of the phage. Finally, we develop a phage-based piezoelectric generator that produces up to 6 nA of current and 400 mV of potential and use it to operate a liquid-crystal display. Because biotechnology techniques enable large-scale production of genetically modified phages, phage-based piezoelectric materials potentially offer a simple and environmentally friendly approach to piezoelectric energy generation." http://bit.ly/K2otv3
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