"Accelerating the process of industrial bacterial host strain development, aimed at increasing productivity, generating new bio-products or utilizing alternative feedstocks, requires the integration of complementary approaches to manipulate cellular metabolism and regulatory networks. Systems metabolic engineering extends the concept of classical metabolic engineering to the systems level by incorporating the techniques used in systems biology and synthetic biology, and offers a framework for the development of the next generation of industrial strains. As one of the most useful tools of systems metabolic engineering, protein design allows us to design and optimize cellular metabolism at a molecular level. Here, we review the current strategies of protein design for engineering cellular synthetic pathways, metabolic control systems and signaling pathways, and highlight the challenges of this subfield within the context of systems metabolic engineering."
"Australian scientists made headlines last month when they revealed that they were close to cloning a frog, Rheobatrachus silus, last seen in the wild three decades ago. If they succeed, it may take another emerging technology to keep that frog alive.
Synthetic biology aims to endow organisms with new sets of genes and new abilities. Along with cloning, it has been portrayed in the press as a hubristic push to do fantastical things: bring back woolly mammoths or resurrect the passenger pigeons that darkened the skies of North America before they were eradicated by nineteenth-century settlers..."
Friedlieb Ferdinand Runge (Born: February 8, 1795, Hamburg
Died: March 25, 1867, Oranienburg) is one of the great forgotten scientists.
I found his work very exiting and actually of relevance for todays systems theory based sciences, such as systems biology and synthetic biology. Runges forgotten discovery of Self-organization is an important contribution to modern science. Very interesting is also his scientific thinking, which is neo-platonic.
He was concerned about notions about reality. What is reality? Which forces build our world? He tried to answer these fundamental questions with his experiments, experiments resulting in stunningly beautiful and fascinating images. These experiments raise highly actual questions about how we perform science and how we achieve scientific truth. Can esthetics and ideas of the mind, such as mathematics, contribute to scientific truth, or should we only trust pure observations?Is our reception of reality caused by a measurable nature around us, or is reality due to our own mental activity? The search for an answer to these questions lead to the discovery of what we call Self-organization of nature. This book follows the path of this discovery from the world of ancient Greek philosophers, over philosophers of the idealistic age, to contemporary science. The fundamental contribution of Friedlieb Ferdinand Runge to this discovery is discussed. Although he is mostly forgotten today, Runge counts as one of the important pioneers of medical and industrial chemistry of the first part of the nineteenth century. Runge made several important discoveries including Atropine, Caffeine, and a precursor to paper chromatography. Runges work on Self-organization of nature is, in the present book, for the first time translated into English. This will hopefully contribute to the rediscovery of an outstanding scientist, and make Runge known to a wider audience. http://amzn.to/106Jwti
"Biomimetic nanoparticles could be an effective treatment against antibiotic-resistant bacteria.
A nanoparticle wrapped in a red blood cell membrane can remove toxins from the body and could be used to fight bacterial infections, according to research published today in Nature Nanotechnology.The results demonstrate that the nanoparticles could be used to neutralize toxins produced by many bacteria, including some that are antibiotic-resistant, and could counteract the toxicity of venom from a snake or scorpion attack, says Liangfang Zhang, a professor of nanoengineering at the University of California, San Diego. Zhang led the research.The “nanosponges” work by targeting so-called pore-forming toxins, which kill cells by poking holes in them. One of the most common classes of protein toxins in nature, pore-forming toxins are secreted by many types of bacteria, including Staphylococcus aureus, of which antibiotic-resistant strains, called MRSA, are endemic in hospitals worldwide and cause tens of thousands of deaths annually. They are also present in many types of animal venom.There are a range of existing therapies designed to target the molecular structure of pore-forming toxins and disable their cell-killing functions. But they must be customized for different diseases and conditions, and there are over 80 families of these harmful proteins, each with a different structure. Using the new nanosponge therapy, says Zhang, “we can neutralize every single one, regardless of their molecular structure.”
*A biomimetic nanosponge that absorbs pore-forming toxins*
by Che-Ming J. Hu,Ronnie H. Fang,Jonathan Copp,Brian T. Luk& Liangfang Zhang
"Detoxification treatments such as toxin-targeted anti-virulence therapy1, 2 offer ways to cleanse the body of virulence factors that are caused by bacterial infections, venomous injuries and biological weaponry. Because existing detoxification platforms such as antisera3, monoclonal antibodies4, small-molecule inhibitors5, 6 and molecularly imprinted polymers7 act by targeting the molecular structures of toxins, customized treatments are required for different diseases. Here, we show a biomimetic toxin nanosponge that functions as a toxin decoy in vivo. The nanosponge, which consists of a polymeric nanoparticle core surrounded by red blood cell membranes, absorbs membrane-damaging toxins and diverts them away from their cellular targets. In a mouse model, the nanosponges markedly reduce the toxicity of staphylococcal alpha-haemolysin (α-toxin) and thus improve the survival rate of toxin-challenged mice. This biologically inspired toxin nanosponge presents a detoxification treatment that can potentially treat a variety of injuries and diseases caused by pore-forming toxins."
1. Introduction2. Addition of C-Centered Radicals to Fullerenes2.1. Metal-Mediated Addition of C-Centered Radicals to C602.1.1. Radical Reactions of C60 Mediated by Decatungstate (W10O324–)2.1.2. Radical Reactions of C60 Mediated by Mn(OAc)3, Fe(ClO4)3, and Cu(OAc)2·H2O2.1.3. Radical Reactions of C60 Mediated by CoCl2dppe2.2. Addition of Fluoroalkyl Radicals to C602.3. Other Reactions of C60 Involving C-Centered Radicals3. Addition of Si-Centered Radicals4. Addition of O- and S-Centered Radicals5. Addition of P-Centered Radicals6. Addition of N-Centered Radicals7. Addition of Metal-Centered Radicals8. Addition of Hydrogen Atom(s)9. Addition of Halogens10. Organofullerenyl Radicals RC60• via Oxidation of Organofullerenyl Anions RC60–11. Fullerene Dimers via Dimerization of RC60• Radicals12. Ion Radical Reactions of Fullerenes12.1. Reactions of Fullerene Radical Anion (C60•–)12.1.1. Addition of Amines to C6012.1.2. Addition of Alkyl Halides to C6012.1.3. Addition of Ketene Silyl Acetals to C6012.1.4. One- and Two-Electron Reduction of C60 with NADH and NAD Dimer Analogues12.1.5. [4 + 2] and [2 + 2] Cycloadditions12.1.6. Reaction of C60 with Cyclopropyl-Substituted Olefins12.2. Reactions of Fullerene Radical Cation (C60•+)13. Radical Reactions of Endohedral Metallofullerenes (EMFs)13.1. Radical Reactions of Paramagnetic M@C8213.2. Radical Reactions of Diamagnetic EMFs13.3. Dichlorophenyl Derivatives of Insoluble EMFs13.4. Disilylation of EMFs14. Radical Reactions of Heterofullerenes15. Radical Scavenging Activity of Fullerenes: Applications in Polymer Science and Biology15.1. Antioxidant Activity of Fullerenes and Their Derivatives15.2. Applications in Polymer Science15.2.1. Anti-Radical Activity of Fullerenes in Radical Polymerization Reactions15.2.2. Anti-Radical Activity of Fullerenes in the Thermal/Thermo-oxidative Degradation of Polymers15.3. Biological Activity and Pharmacological Potential of Fullerenes15.3.1. Malonyl Carboxyfullerenes15.3.2. Hexasulfobutylated Fullerene15.3.3. Dendrofullerene15.3.4. Fullerenols15.3.5. Other Water-Soluble C60 Derivatives16. Summary
"In silicio design plays a fundamental role in the endeavour to synthesise biological systems. In particular, computer-aided design software enables users to manage the complexity of biological entities that is connected to their construction and reconfiguration. The software’s graphical user interface bridges the gap between the machine-readable data on the algorithmic subface of the computer and its human-amenable surface represented by standardised diagrammatic elements. Notations like the Systems Biology Graphical Notation (SBGN), together with interactive operations such as drag & drop, allow the user to visually design and simulate synthetic systems as ‘bio-algorithmic signs’. Finally, the digital programming process should be extended to the wet lab to manufacture the designed synthetic biological systems. By exploring the different ‘faces’ of synthetic biology, I argue that in particular computer-aided design (CAD) is pushing the idea to automatically produce de novo objects. Multifaceted software processes serve mutually aesthetic, epistemic and performative purposes by simultaneously black-boxing and bridging different data sources, experimental operations and community-wide standards. So far, synthetic biology is mainly a product of digital media technologies that structurally mimic the epistemological challenge to take both qualitative as well as quantitative aspects of biological systems into account in order to understand and produce new and functional entities."
by Misirli G, Wipat A, Mullen J, James K, Pocock M, Smith W, Allenby N, Hallinan JS.
"BacillOndex is an extension of the Ondex data integration system, providing a semantically annotated, integrated knowledge base for the model Gram-positive bacterium Bacillus subtilis. This application allows a user to mine a variety of B. subtilis data sources, and analyse the resulting integrated dataset, which contains data about genes, gene products and their interactions. The data can be analysed either manually, by browsing using Ondex, or computationally via a Web services interface. We describe the process of creating a BacillOndex instance, and describe the use of the system for the analysis of single nucleotide polymorphisms in B. subtilis Marburg. The Marburg strain is the progenitor of the widely-used laboratory strain B. subtilis 168. We identified 27 SNPs with predictable phenotypic effects, including genetic traits for known phenotypes. We conclude that BacillOndex is a valuable tool for the systems-level investigation of, and hypothesis generation about, this important biotechnology workhorse. Such understanding contributes to our ability to construct synthetic genetic circuits in this organism."
"In 2010 there were more than 200 million cases of malaria, and at least 655,000 deaths1. The World Health Organization has recommended artemisinin-based combination therapies (ACTs) for the treatment of uncomplicated malaria caused by the parasite Plasmodium falciparum. Artemisinin is a sesquiterpene endoperoxide with potent antimalarial properties, produced by the plantArtemisia annua. However, the supply of plant-derived artemisinin is unstable, resulting in shortages and price fluctuations, complicating production planning by ACT manufacturers2. A stable source of affordable artemisinin is required. Here we use synthetic biology to develop strains of Saccharomyces cerevisiae (baker’s yeast) for high-yielding biological production of artemisinic acid, a precursor of artemisinin. Previous attempts to produce commercially relevant concentrations of artemisinic acid were unsuccessful, allowing production of only 1.6 grams per litre of artemisinic acid3. Here we demonstrate the complete biosynthetic pathway, including the discovery of a plant dehydrogenase and a second cytochrome that provide an efficient biosynthetic route to artemisinic acid, with fermentation titres of 25 grams per litre of artemisinic acid. Furthermore, we have developed a practical, efficient and scalable chemical process for the conversion of artemisinic acid to artemisinin using a chemical source of singlet oxygen, thus avoiding the need for specialized photochemical equipment. The strains and processes described here form the basis of a viable industrial process for the production of semi-synthetic artemisinin to stabilize the supply of artemisinin for derivatization into active pharmaceutical ingredients (for example, artesunate) for incorporation into ACTs. Because all intellectual property rights have been provided free of charge, this technology has the potential to increase provision of first-line antimalarial treatments to the developing world at a reduced average annual price."
"Developing mechanistic models has become an integral aspect of systems biology, as has the need to differentiate between alternative models. Parameterizing mathematical models has been widely perceived as a formidable challenge, which has spurred the development of statistical and optimisation routines for parameter inference. But now focus is increasingly shifting to problems that require us to choose from among a set of different models to determine which one offers the best description of a given biological system. We will here provide an overview of recent developments in the area of model selection. We will focus on approaches that are both practical as well as build on solid statistical principles and outline the conceptual foundations and the scope for application of such methods in systems biology." http://bit.ly/10TK0hR
Arizona State University is beginning to establish its place on the map in the burgeoning field of synthetic biology. Notable strides in research are being made by faculty members and students in t...
Gerd Moe-Behrens's insight:
"Arizona State University is beginning to establish its place on the map in the burgeoning field of synthetic biology.
Notable strides in research are being made by faculty members and students in the School of Biological and Health Systems Engineering, one of ASU’s Ira A. Fulton Schools of Engineering. Assistant professor Karmella Haynes was recently the featured speaker on the subject of advances in synthetic biology for the Arizona Science Center’s New Frontiers in Medical Science lecture series. Some of the data Haynes presented in her talk was derived from research being conducted by bioengineering senior Caroline Hom. The research involving identification and production of reagents that activate genes in different types of cancer cells earned Hom an opportunity to give a talk about her work at the recent annual conference of the Institute of Biological Engineering (IBE) – a rare achievement for an undergraduate...."
Foto: ioengineering doctoral student Behzad Damadzedah (left) works in the lab with assistant professor +Karmella Haynes . They and others at ASU are seeking ways that synthetic biology research can contribute to new or better treatments for various diseases. Damazedah recently reported on his research at the annual Synthetic Biology Engineering Research Center retreat.
"An important requirement for achieving many goals of synthetic biology is the availability of a large repertoire of reprogrammable genetic switches and appropriate transmitter molecules. In addition to engineering genetic switches, the interconnection of individual switches becomes increasingly important for the construction of more complex genetic networks. In particular, RNA-based switches of gene expression have become a powerful tool to post-transcriptionally program genetic circuits. RNAs used for regulatory purposes have the advantage to transmit, sense, process and execute information. We have recently used the hammerhead ribozyme to control translation initiation in a small molecule-dependent fashion. In addition, riboregulators have been constructed in which a small RNA acts as transmitter molecule to control translation of a target mRNA. In this study, we combine both concepts and redesign the hammerhead ribozyme to sense small trans-acting RNAs (taRNAs) as input molecules resulting in repression of translation initiation in Escherichia coli. Importantly, our ribozyme-based expression platform is compatible with previously reported artificial taRNAs, which were reported to act as inducers of gene expression. In addition, we provide several insights into key requirements of riboregulatory systems, including the influences of varying transcriptional induction of the taRNA and mRNA transcripts, 5′-processing of taRNAs, as well as altering the secondary structure of the taRNA. In conclusion, we introduce an RNA-responsive ribozyme-based expression system to the field of artificial riboregulators that can serve as reprogrammable platform for engineering higher-order genetic circuits." http://bit.ly/ZymZyw
"This article provides an overview of how three branches of science, namely Systems Biology, Synthetic Biology and Control Theory might be interlaced to help solve relevant problems in medicine and biotechnology. It aims to provide for control engineers the basic background to understand the roles played (and challenges posed) by these fields during the set up of biological control systems. It also shows how the concepts from Supervisory Control Theory can be adapted to treat cellular control problems."
*Regeneration and experimental orthotopic transplantation of a bioengineered kidney*
by Jeremy J Song,Jacques P Guyette,Sarah E Gilpin,Gabriel Gonzalez,Joseph P Vacanti& Harald C Ott
"Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidney function would address donor organ shortage and the morbidity associated with immunosuppression. Such a bioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo."
*Metabolic tinker: an online tool for guiding the design of synthetic metabolic pathways*
by Kent McClymont and Orkun S. Soyer
"One of the primary aims of synthetic biology is to (re)design metabolic pathways towards the production of desired chemicals. The fast pace of developments in molecular biology increasingly makes it possible to experimentally redesign existing pathways and implement de novo ones in microbes or using in vitro platforms. For such experimental studies, the bottleneck is shifting from implementation of pathways towards their initial design. Here, we present an online tool called ‘Metabolic Tinker’, which aims to guide the design of synthetic metabolic pathways between any two desired compounds. Given two user-defined ‘target’ and ‘source’ compounds, Metabolic Tinker searches for thermodynamically feasible paths in the entire known metabolic universe using a tailored heuristic search strategy. Compared with similar graph-based search tools, Metabolic Tinker returns a larger number of possible paths owing to its broad search base and fast heuristic, and provides for the first time thermodynamic feasibility information for the discovered paths. Metabolic Tinker is available as a web service at http://osslab.ex.ac.uk/tinker.aspx. The same website also provides the source code for Metabolic Tinker, allowing it to be developed further or run on personal machines for specific applications."
"The parts-based engineering approach in synthetic biology aims to create pre-characterised biological parts that can be used for the rational design of novel functional systems. Given the context-sensitivity of biological entities, a key question synthetic biologists have to address is what properties these parts should have so that they give a predictable output even when they are used in different contexts. In the first part of this paper I will analyse some of the answers that synthetic biologists have given to this question and claim that the focus of these answers on parts and their properties does not allow us to tackle the problem of context-sensitivity. In the second part of the paper, I will argue that we might have to abandon the notions of parts and their properties in order to understand how independence in biology could be achieved. Using Robert Cummins’ account of functional analysis, I will then develop the notion of a capacity and its condition space and show how these notions can help to tackle the problem of context-sensitivity in biology."
"Synthetic biology is often presented as a promissory field that ambitions to produce novelty by design. The ultimate promise is the production of living systems that will perform new and desired functions in predictable ways. Nevertheless, realizing promises of novelty has not proven to be a straightforward endeavour. This paper provides an overview of, and explores the existing debates on, the possibility of designing living systems de novo as they appear in interdisciplinary talks between engineering and biological views within the field of synthetic biology. To broaden such interdisciplinary debates, we include the views from the social sciences and the humanities and we point to some fundamental sources of disagreement within the field. Different views co-exist, sometimes as controversial tensions, but sometimes also pointing to integration in the form of intermediate positions. As the field is emerging, multiple choices are possible. They will inform alternative trajectories in synthetic biology and will certainly shape its future. What direction is best is to be decided in reflexive and socially robust ways."
by Immethun CM, Hoynes-O'Connor AG, Balassy A, Moon TS.
"Microorganisms transform inexpensive carbon sources into highly functionalized compounds without toxic by-product generation or significant energy consumption. By redesigning the natural biosynthetic pathways in an industrially suited host, microbial cell factories can produce complex compounds for a variety of industries. Isoprenoids include many medically important compounds such as antioxidants and anticancer and antimalarial drugs, all of which have been produced microbially. While a biosynthetic pathway could be simply transferred to the production host, the titers would become economically feasible when it is rationally designed, built, and optimized through synthetic biology tools. These tools have been implemented by a number of research groups, with new tools pledging further improvements in yields and expansion to new medically relevant compounds. This review focuses on the microbial production of isoprenoids for the health industry and the advancements though synthetic biology." http://bit.ly/YQISgQ
I found these 4 papers in todays edition of Science:
1) The *Vertebral Column* of Australopithecus sediba
2) The *Lower Limb* and Mechanics of Walking in Australopithecus sediba
3) The *Upper Limb* of Australopithecus sediba
4) Mosaic Morphology in the *Thorax* of Australopithecus sediba
All awesome work!
I cite them because, the scientific view behind this work reminds me of a woodcut by Hokusai (see photo).
This picture provides us with a nice illustration of the problem of reductionism versus holism. We see blind men exploring an elephant. One blind researcher is studying the back, another the neck, one blind researcher explores the tail, the next the front part of the tooth and so on. Nobody gets the whole picture.Big data have brought science to a point where we might wish to change the perspective from reduction to holism. The reductionistic approach has successfully identified many components and interactions, but does not provide convincing explanation for how a complex system, such as a living being work. Today we are in the situation that we have huge amounts of data from high throughput experiments, but we do not understand the whole picture.Huge amounts of data and facts available mean lesser need for models. The number speaks for itself.Holistic thinking means beginning with the understanding of the highest abstraction level. Our scientific approach should maybe do the same. First understand the whole picture, then the details.
by Tae-il Kim, Jordan G. McCall, Yei Hwan Jung, Xian Huang, Edward R. Siuda, Yuhang Li, Jizhou Song, Young Min Song, Hsuan An Pao, Rak-Hwan Kim, Chaofeng Lu, Sung Dan Lee, Il-Sun Song, GunChul Shin, Ream Al-Hasani, Stanley Kim, Meng Peun Tan, Yonggang Huang, Fiorenzo G. Omenetto, John A. Rogers, Michael R. Bruchas
"Successful integration of advanced semiconductor devices with biological systems will accelerate basic scientific discoveries and their translation into clinical technologies. In neuroscience generally, and in optogenetics in particular, the ability to insert light sources, detectors, sensors, and other components into precise locations of the deep brain yields versatile and important capabilities. Here, we introduce an injectable class of cellular-scale optoelectronics that offers such features, with examples of unmatched operational modes in optogenetics, including completely wireless and programmed complex behavioral control over freely moving animals. The ability of these ultrathin, mechanically compliant, biocompatible devices to afford minimally invasive operation in the soft tissues of the mammalian brain foreshadow applications in other organ systems, with potential for broad utility in biomedical science and engineering."
The ability to engineer novel functionality within cells, to quantitatively control cellular circuits, and to manipulate the behaviors of populations, has many important applications in biotechnology and biomedicine. These applications are only beginning to be explored. In this review, we advocate the use of feedback control as an essential strategy for the engineering of robust homeostatic control of biological circuits and cellular populations. We also describe recent works where feedback control, implemented in silico or with biological components, was successfully employed for this purpose."
Thiprampai Thamamongood, Nathaniel Z. L. Lim, Trevor Y.H. Ho, Shotaro Ayukawa, Daisuke Kiga, and King L. Chow
"The main goal of synthetic biology is to create new biological modules that augment or modify the behavior of living organisms in performing different tasks. These modules are useful in a wide range of applications, such as medicine, agriculture, energy and environmental remediation. The concept is simple, but a paradigm shift needs to be in place among future life scientists and engineers to embrace this new direction. The international Genetically Engineered Machine (iGEM) competition fits this purpose well as a synthetic biology competition mainly for undergraduate students. Participants design and construct biological devices using standardized and customized biological parts that are then characterized and submitted to an existing and ever expanding library. Overall, iGEM is an eye-opening learning experience for undergraduate students. It has made a strong educational impact on participating students and cultivated a future cohort of synthetic biology practitioners and ambassadors. "
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