Evan J Olson, Jeffrey J Tabor "Synthetic biology is improving our understanding of and ability to control living organisms. To date, most progress has been made by engineering gene expression. However, computational and genetically encoded tools that allow protein activity and protein–protein interactions to be controlled on their natural time and length scales are emerging. These technologies provide a basis for the construction of post-translational circuits, which are capable of fast, robust and highly spatially resolved signal processing. When combined with their transcriptional and translational counterparts, synthetic post-translational circuits will allow better analysis and control of otherwise intractable biological processes such as cellular differentiation and the growth of tissues.
Highlights ► Phytochromes and LOV domains are being used for spatiotemporal control of protein activity in cells. ► Computational redesign of CDC42/ISTN interface generates orthogonal signaling pathway. ► Computation-guided design of 180 pmKd PPI paves way for the design of modular protein networks. ► Stem cell differentiation can be controlled with synthetic transcriptional and post-translational networks."
Wickham SF, Bath J, Katsuda Y, Endo M, Hidaka K, Sugiyama H, Turberfield AJ. "Synthetic molecular motors can be fuelled by the hydrolysis or hybridization of DNA. Such motors can move autonomously and programmably, and long-range transport has been observed on linear tracks. It has also been shown that DNA systems can compute. Here, we report a synthetic DNA-based system that integrates long-range transport and information processing. We show that the path of a motor through a network of tracks containing four possible routes can be programmed using instructions that are added externally or carried by the motor itself. When external control is used we find that 87% of the motors follow the correct path, and when internal control is used 71% of the motors follow the correct path. Programmable motion will allow the development of computing networks, molecular systems that can sort and process cargoes according to instructions that they carry, and assembly lines that can be reconfigured dynamically in response to changing demands." http://1.usa.gov/L0Ku1p
"Can cells become little computers? And how does technological progress challenge our ideas about free will, intelligence, and the purpose of human life? Martin Eiermann sat down with the computer scientist Stephen Wolfram to discuss these questions..." http://bit.ly/N69FeC
Brown Stanford iGEM talks with Raymond McCauley- career bioinformaticist, entrepreneur, and futurist. Raymond McCauley is Chair of the Biotechnology Track an...
" Synthetic biology (SynBio) can be defined as the design and construction of new biological parts, devices and systems. The field has now advanced from first-generation understanding to smarter engineering. This focus issue of BTJ gives several examples; e.g. Morey et al. review the current status of plant synthetic biology and the crosstalk between endogenous and synthetic components"
"The Technology Strategy Board and The Synthetic Biology Special Interest Group are organising a series of consortia-building workshops to promote the competition for feasibility funding: "Advancing the Industrial Application of Synthetic Biology" The workshops will enable delegates to get a better understanding the competition scope and application process ahead of the official opening of the call on October 8th and encourage networking opportunities from which collaborations may develop. Synthetic biology offers new potential to produce chemicals in a smarter more sustainable way. More information on the events can be found through the links below. New Frontiers in Synthetic Biology, 10 July 2012, Ambassadors Bloomsbury Hotel, London New Frontiers in Synthetic Biology Regional workshop - Edinburgh, 24 July 2012, The George Hotel, Edinburgh New Frontiers in Synthetic Biology Regional workshop - Manchester, 25 July 2012, The Hilton Manchester Deansgate Hotel, Manchester For more information on the Synthetic Biology Special Interest Group can be found here.."
Amber Dance "Working at the crossroads of biology and engineering, synthetic biologists are crafting genes, proteins, and organisms that evolution never came up with. They are creating bacteria that produce biofuels and yeast cells that manufacture medicines. They are swapping promoters, ribosome-binding sequences, and open reading frames as if they were Lego bricks.
“We are no longer constrained by what Mother Nature gives us,” says Claes Gustafsson, cofounder of the DNA synthesis company DNA2.0, in Menlo Park, California.
Now, the constraint is the toolkit. Traditional biologists can work with DNA sequences using a simple viewer or editor, but “the engineers need a whole new suite of tools,” says Natalie Kuldell, who teaches biological engineering at MIT.
The synthetic biologist’s mind-set is all about parts, those nucleic acid bricks they shuffle to design a desired gene or gene network. Previously, researchers dealt with plain-text sequences, in word-processing or spreadsheet files. Copying and pasting, “it’s very easy to make mistakes,” says Avi Robinson-Mosher, a postdoc who designs cancer drugs at Harvard’s Wyss Institute for Biologically Inspired Engineering. Synthetic biologists need computer-aided design tools akin to those used by other kinds of engineers. ...." Fortunately, many synthetic biologists have backgrounds in computers and engineering, and are developing software of their own. Some programs make drawing up the plans for a new plasmid so effortless that high school students and untrained bio-hobbyists can do it. Others include simulators so researchers can predict how a new genetic circuit will work. Several are open-source, so computer-savvy biologists can customize them.
"The question about how art and science interact, and if art is an integrated part of scientific work, or should be banned from science, leads us back to discussions of the ancient Greek philosophers and their precursors. The fundamental question was: What is reality? Can we understand the world around us with the help of our senses, or is the world around us a product of our mental concepts? The answers to these questions never were straightforward, and have been heavily discussed during the last 2000 years. During the different periods of history, sometimes it was en vogue to believe that reality is defined by our senses (materialism) other times people preferred to believe that reality is mental (idealism).
The concept of idealism was profoundly formulated for the first time by Plato (428/7 - 348/7 BC). Later it was enlivened by different Neo-Platonic movements. E.g. Leonardo Da Vinci (1452 –1519), a follower of Neo-Platonism, did not make a clear distinction between art and science. If the reality of the world basically is a mental product, all mental products including art, play an as equally important role.
Idealistic scientific thinking fell out of favor by the end of the nineteenth century. The main paradigm was now materialism. Idealistic thinking was highly criticized as unscientific. The external world and its observation by experiments became the main subject of science. Reflection about how our brain is structuring the world, and its meaning for scientific discovery were excluded from scientific methodology. Materialistic, scientific approach survived as a leading paradigm until today. Such materialistic orientated science banned art and artistic thinking from science. Art was viewed as a separate area, which could not give valuable contributions to scientific discovery.
However, a number of twentieth century scientists are known to have concerned themselves with Neo-Platonic, artistic thinking, such as earlier described in e.g. Goethes (1749 – 1832) theory of color, a theory focused on the mental reception of color. Among these modern scientists are the logician and mathematician Kurt Goedel (1906 - 1978), the theoretical physicist Werner Heisenberg (1901 - 1976) the mathematical physicist and pioneer of chaos theory Mitchell Feigenbaum (born 1944), to mention a few. Feigenbaum has even said, “Goethe was right about color”! All the above-mentioned use mathematics as their scientific tool. ....." http://bit.ly/ORwuZg
Avi Schroeder, Michael S. Goldberg, Christian Kastrup, Yingxia Wang, Shan Jiang, Brian J. Josep, Christopher G. Levins, Sneha T. Kannan, Robert Langer, and Daniel G. Anderson
"The development of responsive nanomaterials, nanoscale systems that actively respond to stimuli, is one general goal of nanotechnology. Here we develop nanoparticles that can be controllably triggered to synthesize proteins. The nanoparticles consist of lipid vesicles filled with the cellular machinery responsible for transcription and translation, including amino acids, ribosomes, and DNA caged with a photolabile protecting group. These particles served as nanofactories capable of producing proteins including green fluorescent protein (GFP) and enzymatically active luciferase. In vitro and in vivo, protein synthesis was spatially and temporally controllable, and could be initiated by irradiating micrometer-scale regions on the time scale of milliseconds. The ability to control protein synthesis inside nanomaterials may enable new strategies to facilitate the study of orthogonal proteins in a confined environment and for remotely activated drug delivery."
"Only a small fraction of the immense diversity of plant metabolism has been explored for the production of new medicines and other products important to human well-being. The availability of inexpensive high-throughput sequencing is rapidly expanding the number of species that can be investigated for the speedy discovery of previously unknown enzymes and pathways. Exploitation of these resources is being carried out through interdisciplinary synthetic and chemical biology to engineer pathways in plant and microbial systems for improving the production of existing medicines and to create libraries of biologically active products that can be screened for new drug applications." http://1.usa.gov/MgVAjU
Elliot Harmon "In their excellent Washington Post opinion piece, Matt Cooper and Elizabeth Wiley suggest that federally funded research should be freely accessible over the Internet. They argue that when students lose their access to academic databases after graduation, society doesn’t get the same benefits it could from that research:
Students’ library cards are a passport to the specialized knowledge found in academic journal articles — covering medicine and math, computer science and chemistry, and many other fields. These articles contain the cutting edge of our understanding and capture the genius of what has come before. In no uncertain terms, access to journals provides critical knowledge and an up-to-date education for tomorrow’s doctors, researchers and entrepreneurs. But should that access cease at graduation? Or would you rather a graduating medical student, perhaps your future doctor, be able to keep up with the latest advances? Would you rather an ambitious graduate student feel comfortable leaving the academy to found the next Google, knowing she still has access to the latest insight in her field and is able to build upon it? Cooper and Wiley’s organizations — the National Association of Graduate-Professional Students and the American Medical Student Association, respectively — joined Creative Commons and many other allies in support of a petition on Whitehouse.gov for free access to scientific journal articles arising from taxpayer-funded research. The petition quickly reached its goal of 25,000 signatures, sending a clear message that it’s time for the government to rethink open access policies."
Plastic Republic Our mission is to clean plastic pollution from the oceans using synthetic organisms, with the vision of creating artificial islands! What are we doing? Plastic Republic is a synthetic biology project.
Kanjiro Miyata , Nobuhiro Nishiyama and Kazunori Kataoka
"Polymeric materials have been extensively developed as a delivery vehicle for nucleic acids over the past two decades. Many previous studies have demonstrated that synthetic delivery vehicles can be highly functionalized by chemical approaches to overcome biological barriers in nucleic acid delivery, similar to viruses. Based on our current knowledge, this tutorial review describes rational strategies in the design of polymeric materials to achieve construction of the versatile vehicles, that is “artificial viruses”, for successful gene therapy, especially focusing on the chemical structures with the minimal adverse effects."
by Paul S. Freemont (Author, Editor), Richard I Kitney (Author), Geoff Baldwin (Author), Travis Bayer (Author), Robert Dickinson (Author), Tom Ellis (Author), Karen Polizzi (Author), Guy-Bart Stan (Author), Richard I. Kitney (Editor)
"Synthetic Biology - A Primer" gives a broad overview of the emerging field of synthetic biology and the foundational concepts on which it is built. It will be of interest to final year undergraduates, postgraduates and established researchers who are interested in learning about this exciting new field. The book introduces readers to fundamental concepts in molecular biology and engineering and then explores the two major themes for synthetic biology, namely 'bottom-up' and 'top-down' engineering approaches. 'Top-down' engineering utilises a conceptual framework of engineering and systematic design to build new biological systems by integrating robustly characterised biological parts into an existing system through the use of extensive mathematical modelling. The 'bottom-up' approach involves the design and building of synthetic protocells using basic chemical and biochemical building blocks from scratch. Exemplars of cutting-edge applications designed using synthetic biology principles are presented, including the production of novel biofuels from renewable feedstocks, microbial synthesis of pharmaceuticals and fine chemicals, and the design and implementation of biosensors to detect infections and environmental waste. The book also uses the Internationally Genetically Engineered Machine (iGEM) competition to illustrate the power of synthetic biology as an innovative research and training science. Finally, the primer includes a chapter on the ethical, legal and societal issues surrounding synthetic biology, illustrating the integration of social sciences in synthetic biology research."
Karsten Temme, Rena Hill, Thomas H. Segall-Shapiro, Felix Moser and Christopher A. Voigt
"Synthetic genetic sensors and circuits enable programmable control over the timing and conditions of gene expression. They are being increasingly incorporated into the control of complex, multigene pathways and cellular functions. Here, we propose a design strategy to genetically separate the sensing/circuitry functions from the pathway to be controlled. This separation is achieved by having the output of the circuit drive the expression of a polymerase, which then activates the pathway from polymerase-specific promoters. The sensors, circuits and polymerase are encoded together on a ‘controller’ plasmid. Variants of T7 RNA polymerase that reduce toxicity were constructed and used as scaffolds for the construction of four orthogonal polymerases identified via part mining that bind to unique promoter sequences. This set is highly orthogonal and induces cognate promoters by 8- to 75-fold more than off-target promoters. These orthogonal polymerases enable four independent channels linking the outputs of circuits to the control of different cellular functions. As a demonstration, we constructed a controller plasmid that integrates two inducible systems, implements an AND logic operation and toggles between metabolic pathways that change Escherichia coli green (deoxychromoviridans) and red (lycopene). The advantages of this organization are that (i) the regulation of the pathway can be changed simply by introducing a different controller plasmid, (ii) transcription is orthogonal to host machinery and (iii) the pathway genes are not transcribed in the absence of a controller and are thus more easily carried without invoking evolutionary pressure." http://bit.ly/KMwzr3
Martin Jinek, Krzysztof Chylinski, Ines Fonfara, Michael Hauer, Jennifer A. Doudna, Emmanuelle Charpentier
"CRISPR/Cas systems provide bacteria and archaea with adaptive immunity against viruses and plasmids by using crRNAs to guide the silencing of invading nucleic acids. We show here that in a subset of these systems, the mature crRNA base-paired to trans-activating tracrRNA forms a two-RNA structure that directs the CRISPR-associated protein Cas9 to introduce double-stranded (ds) breaks in target DNA. At sites complementary to the crRNA-guide sequence, the Cas9 HNH nuclease domain cleaves the complementary strand while the Cas9 RuvC-like domain cleaves the noncomplementary strand. The dual-tracrRNA:crRNA, when engineered as a single RNA chimera, also directs sequence-specific Cas9 dsDNA cleavage. Our study reveals a family of endonucleases that use dual RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing." http://bit.ly/QJg7MS
Comment: "*Programmable RNA Complex Could Speed Genome Editing in the Lab* For bacteria, snipping apart DNA that bears certain signature sequences is a defense mechanism. For scientists working in the lab, the same strategy can be a powerful research tool. With a newly discovered component of an adaptive bacterial immune system, scientists have identified a targeted method of slicing DNA that they say can be easily customized for a variety of applications in the lab.
Tools that snip apart DNA strands in defined locations are essential for editing genomes in the laboratory to study or alter gene function. To target the specific site in the genome they are interested in, researchers often have to design and produce a protein that will recognize and bind to that particular DNA sequence, a laborious and time-consuming process.
“This system offers a straightforward way to cleave any desired site in a genome, which could be used to introduce new genetic information by coupling it to well-known cellular DNA recombination mechanisms.” Jennifer A. Doudna...." http://bit.ly/MyJGkY
"In this article, we propose a domain specific language, GUBS (Genomic Unified Behavior Specification), dedicated to the behavioral specification of synthetic biological devices, viewed as discrete open dynamical systems. gubs is a rule-based declarative language. By contrast to a closed system, a program is always a partial description of the behavior of the system. The semantics of the language accounts the existence of some hidden non-specified actions possibly altering the behavior of the programmed device. The compilation framework follows a scheme similar to automatic theorem proving, aiming at improving synthetic biological design safety." http://bit.ly/OQ19aD
"Covering: 2005 to 2012 Natural product analogue generation is important, providing tools for chemical biology, enabling structure activity relationship determination and insight into the way in which natural products interact with their target biomolecules. The generation of analogues is also often necessary in order to improve bioavailability and to fine tune compounds' activity. This review provides an overview of the catalogue of approaches available for accessing series of analogues. Over the last few years there have been major advances in genome sequencing and the development of tools for biosynthetic pathway engineering; it is therefore becoming increasingly easy to combine molecular biology and synthetic organic chemistry in order to enable expeditious access to series of natural products. This review outlines the various ways of combining biology and chemistry that have been applied to analogue generation, drawing upon a series of examples to illustrate each approach." http://1.usa.gov/KTj39H
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