"The military-industrial complex just got a little bit livelier. Quite literally.
That’s because Darpa, the Pentagon’s far-out research arm, has kicked off a program designed to take the conventions of manufacturing and apply them to living cells. Think of it like an assembly line, but one that would churn out modified biological matter — man-made organisms — instead of cars or computer parts.
The program, called “Living Foundries,” was first announced by the agency last year. Now, Darpa’s handed out seven research awards worth $15.5 million to six different companies and institutions. Among them are several Darpa favorites, including the University of Texas at Austin and the California Institute of Technology. Two contracts were also issued to the J. Craig Venter Institute. Dr. Venter is something of a biology superstar: He was among the first scientists to sequence a human genome, and his institute was, in 2010, the first to develop an entirely synthetic organism.
“Living Foundries” aspires to turn the slow, messy process of genetic engineering into a streamlined and standardized one. Of course, the field is already a burgeoning one: Scientists have tweaked cells in order to develop renewable petroleum and spider silk that’s tough as steel. And a host of companies are investigating the pharmaceutical and agricultural promise lurking — with some tinkering, of course — inside living cells......" http://bit.ly/LfrB67
7+ years for a scientific project - We can do better!
"Darpa notes, even the most cutting-edge synthetic biology projects “often take 7+ years and tens to hundreds of millions of dollars” to complete." http://bit.ly/JpJKSV I think this is ridiculous. We do not really need 7 years to do a scientific project.
The main reason for this is that we still do science in the old fashioned way.
Basically we have with the internet got a tool to do this much quicker and some projects have done so e.g. see Linux development or the iGem competition. In this last projects students can do in 3 month what a post doc before did in 3 years. Collaborative intelligence and cloud collaboration have a huge potential to seed up. However, fear for our career held many scientist back to adapt to science2.0. The science business model high impact factor paper, tax money paid position is outdated, however the one, which feed us. As a consequence it take 1 to 2 years to get grants, 3 years to do the project as a single post doc (scientific collaboration is mostly on the papers for grant applications), and 2 years to get it published with many rounds of meaningless rejections ad revisions. Thus you end up with a typically time use of about 7 years instead of 3 month. Cloud collaboration will change this, hopefully soon.
"Andrew Maynard, Ph.D., focuses on the responsible development and use of emerging technologies, and on innovative approaches to addressing emergent risks. An international expert on nanotechnology, he is a professor of risk science and environmental health sciences at University of Michigan School of Public Health." http://bit.ly/Lowedr
Bringing next-generation therapeutics to the clinic through synthetic biology
by Lukasz J Bugaj, David V Schaffer "Highlights ► Synthetic biology tools are being applied towards the clinical development of enhanced therapeutics. ► Engineered genetic circuits can create ‘smart’ drugs with sensing and actuating capabilities. ► Therapeutic devices may be delivered through viral vectors, encapsulated cells, or bacteria. ► With initial clinical trials underway, safety will be the first priority." "Recent advances in synthetic biology have created genetic tools with the potential to enhance the specificity, dynamic control, efficacy, and safety of medical treatments. Interfacing these genetic devices with human patients may thus bring about more efficient treatments or entirely new solutions to presently intractable maladies. Here we review engineered circuits with clinical potential and discuss their design, implementation, and validation." http://bit.ly/LctrVt
"Computation is defining trait of biological systems and a broad framework that captures the complex adaptive nature of molecules, cells and organisms. Computation is also at the core of the genotype-phenotype mapping, since it provides a natural framework to define function in a self-consistent way. The study of existing biological systems (from signalling cas- cades to ant colonies or brains) as well as the evolution of synthetic in silico networks performing computations reveals a number of nontrivial patterns of organization, sometimes in clear conflict with standard view of engineering or optimiza- tion. In spite of our increasing knowledge, there is a lack of a theoretical framework where computation and its pos- sible forms is integrated within a general picture. Synthetic biology provides a new avenue where engineered molecular circuits can be implemented to perform non-standard com- putations. Here we review recent advances in the domain of multicellular synthetic computing and suggest a potential morphospace of computational systems including both stan- dard and non-standard approximations."
"UC Berkeley’s Understanding Science resource website makes excellent use of interactive schemata to reinforce the scientific method. The flow of information facilitates both global and sequential learning. The community analysis sphere (below) deals with quality control—one of two major collaboratory elements to use crowdsourcing. Students are encouraged to review the work of others, both past and present, and the mention of individual scientists reinforces the value of the collective. Further development considerations include smartphone adaptability and 3D visualization. ...."
"The goal of synthetic biology is to make the construction of novel biological systems into a practical and useful engineering discipline. The key is the development of an engineering methodology based on standardized and well-characterized interchangeable parts. Biological systems can be a basis for practical programmable materials, providing an engineering substrate with exquisite control over and response to the chemical world. The consequences of synthetic biology will be as great as the development of chemical engineering from alchemy, with enormous and as perhaps unimaginable implications for materials science and medicine. The range of applications for synthetic biology is vast, encompassing but not limited to: diagnostics, therapeutics, sensors, environmental remediation, energy production, and a host of other biomolecular and chemical manufacturing outputs. Synthetic biology can also help us gain valuable insight into fundamental biological principles and improve our quantitative understanding of the living world.
The mission of the Synthetic Biology Center at MIT is to develop and advance the engineering discipline for this emerging field.
The Center will be structured around three layered Thrusts:
Foundations Thrust, focused on creating an infrastructure of synthetic biology tools and capabilities. Systems Engineering Thrust, for engineering highly sophisticated biological systems rapidly, efficiently, and reliably. Grand Challenge Applications Thrust, for select areas where synthetic biology provides unique opportunities and capabilities." http://bit.ly/MzKXrI
Christopher Voigt "We are developing a basis by which cells can be programmed like robots to perform complex, coordinated tasks for pharmaceutical and industrial applications. We are engineering new sensors that give bacteria the senses of touch, sight, and smell. Genetic circuits - analogous to their electronic counterparts - are built to integrate the signals from the various sensors. Finally, the output of the gene circuits is used to control cellular processes. We are also developing theoretical tools from statistical mechanics and non-linear dynamics to understand how to combine genetic devices and predict their collective behavior."
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
Fidelity Investments is one of the world's largest providers of financial services, with assets under administration of $3.4 trillion, including managed assets of $1.5 trillion, as of Dec. 31, 2011.
On April 27th, 2012 the Stanford Program in Law Science and Technology hosted the Stanford Law School Conference on Intellectual Property Law and the Bioscie...
Rewritable digital data storage in live cells via engineered control of recombination directionality
by Jerome Bonnet, Pakpoom Subsoontorn, and Drew Endy "The use of synthetic biological systems in research, healthcare, and manufacturing often requires autonomous history-dependent behavior and therefore some form of engineered biological memory. For example, the study or reprogramming of aging, cancer, or development would benefit from genetically encoded counters capable of recording up to several hundred cell division or differentiation events. Although genetic material itself provides a natural data storage medium, tools that allow researchers to reliably and reversibly write information to DNA in vivo are lacking. Here, we demonstrate a rewriteable recombinase addressable data (RAD) module that reliably stores digital information within a chromosome. RAD modules use serine integrase and excisionase functions adapted from bacteriophage to invert and restore specific DNA sequences. Our core RAD memory element is capable of passive information storage in the absence of heterologous gene expression for over 100 cell divisions and can be switched repeatedly without performance degradation, as is required to support combinatorial data storage. We also demonstrate how programmed stochasticity in RAD system performance arising from bidirectional recombination can be achieved and tuned by varying the synthesis and degradation rates of recombinase proteins. The serine recombinase functions used here do not require cell-specific cofactors and should be useful in extending computing and control methods to the study and engineering of many biological systems." http://bit.ly/K5n33R Comment Nature, News: Rewritable memory encoded into DNA by Erika Check Hayden "Researchers have encoded a form of rewritable memory into DNA. The arduous work involved in building the system is almost as notable as the achievement itself, says Drew Endy of Stanford University in California who led the work, which is published today in Proceedings of the National Academy of Sciences1. Synthetic biologists have long sought to devise biological data-storage systems because they could be useful in a variety of applications, and because data storage will be a fundamental function of the digital circuits that the field hopes to create in cells. DNA can be programmed to act as a biological data-storage device. Rewritable biological memory circuits have been made previously, for instance from systems of transcription factors, which can be used to shut gene expression on or off in a cell. In such systems, once the memory state of the circuit is set, it can be erased and encoded with a new memory state, as is done in everyday devices such as personal computers. Endy’s group attempted to create a rewritable memory system by splicing genetic elements from a bacteriophage — a bacterium-infecting virus — into the DNA of the bacterium Escherichia coli. ..." http://bit.ly/Ktd2wt
"The Synthetic Biology Engineering Research Center (SynBERC) is a multi-institution research effort to lay the foundation for the emerging field of synthetic biology. SynBERC’s vision is to catalyze biology as an engineering discipline by developing the foundational understanding and technologies to allow researchers to design and build standardized, integrated biological systems to accomplish many particular tasks. In essence, we are making biology easier to engineer.
Just as technicians now assemble electronic devices from commercial, off-the-shelf parts, SynBERC foresees a day when synthetic biologists will design biological systems from scratch and assemble them using well-characterized biological parts, devices, and chasses. SynBERC brings together biologists, engineers, and human scientists from world-class institutions to produce the tools, techniques, and scientific understanding needed to design and construct a broad range of biological tools for health, energy, environment and, ultimately, human welfare." http://bit.ly/iE5zMP
is working to make the engineering of new complex function in cells vastly more efficient, reliable, predictable, and safe. Its breakthroughs will speed the development of biologically engineered solutions to pressing global problems related to health, materials, energy, environment, and security. http://bit.ly/nTAuh0
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. ...."
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"Darpa notes, even the most cutting-edge synthetic biology projects “often take 7+ years and tens to hundreds of millions of dollars” to complete." http://bit.ly/JpJKSV
I think this is ridiculous. We do not really need 7 years to do a scientific project.
The main reason for this is that we still do science in the old fashioned way.
Basically we have with the internet got a tool to do this much quicker and some projects have done so e.g. see Linux development or the iGem competition. In this last projects students can do in 3 month what a post doc before did in 3 years. Collaborative intelligence and cloud collaboration have a huge potential to seed up. However, fear for our career held many scientist back to adapt to science2.0. The science business model high impact factor paper, tax money paid position is outdated, however the one, which feed us. As a consequence it take 1 to 2 years to get grants, 3 years to do the project as a single post doc (scientific collaboration is mostly on the papers for grant applications), and 2 years to get it published with many rounds of meaningless rejections ad revisions. Thus you end up with a typically time use of about 7 years instead of 3 month. Cloud collaboration will change this, hopefully soon.