Zhen Gu †‡§¶, Alex A. Aimetti †‡§, Qun Wang †‡,Tram T. Dang †‡, Yunlong Zhang †‡§, Omid Veiseh†‡§, Hao Cheng †‡#, Robert S. Langer †‡§, andDaniel G. Anderson †‡§*
"Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivostudies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days."
"Purple bacteria are among Earth’s oldest organisms, and among its most efficient in turning sunlight into usable chemical energy. Now, a key to their light-harvesting prowess has been explained through a detailed structural analysis by scientists at MIT.
A ring-shaped molecule with an unusual ninefold symmetry is critical, the researchers found. The circular symmetry accounts for its efficiency in converting sunlight, and for its mechanical durability and strength. The new analysis, carried out by professors of chemistry Jianshu Cao and the late Robert Silbey, postdoc Liam Cleary, and graduate students Hang Chen and Chern Chuang, has been published in the Proceedings of the National Academy of Sciences."
*Optimal fold symmetry of LH2 rings on a photosynthetic membrane*
Liam Cleary, Hang Chen, Chern Chuang, Robert J. Silbey, and Jianshu Cao
*An intriguing observation of photosynthetic light-harvesting systems is the N-fold symmetry of light-harvesting complex 2 (LH2) of purple bacteria. We calculate the optimal rotational configuration of N-fold rings on a hexagonal lattice and establish two related mechanisms for the promotion of maximum excitation energy transfer (EET). (i) For certain fold numbers, there exist optimal basis cells with rotational symmetry, extendable to the entire lattice for the global optimization of the EET network. (ii) The type of basis cell can reduce or remove the frustration of EET rates across the photosynthetic network. We find that the existence of a basis cell and its type are directly related to the number of matching points S between the fold symmetry and the hexagonal lattice. The two complementary mechanisms provide selection criteria for the fold number and identify groups of consecutive numbers. Remarkably, one such group consists of the naturally occurring 8-, 9-, and 10-fold rings. By considering the inter-ring distance and EET rate, we demonstrate that this group can achieve minimal rotational sensitivity in addition to an optimal packing density, achieving robust and efficient EET. This corroborates our findings i and ii and, through their direct relation to S, suggests the design principle of matching the internal symmetry with the lattice order.* http://bit.ly/1490KnO
Synthetic biology and the World Wide Web are teaming up to modernize our flu vaccines
by Taylor Kubota
"Four years ago, the H1N1 swine flu emerged, launching the United States into its first influenza pandemic in 40 years. By the spring of 2010, the Centers for Disease Control and Prevention (CDC) estimated that at least 43 million Americans had been infected with the virus. Even after this landmark flu season ended, its impact inspired Dr. Philip Dormitzer and his colleagues to make some radical changes to the way we create flu vaccines. When the H1N1 season reached its peak in late October of 2009, the vaccines were only just becoming available. In general, vaccines aren’t obtainable until about five or six months after a virus is first identified. Now, Dormizter, the leader of viral research at the private pharmaceutical lab Novartis, is using downloadable DNA sequences and custom-made synthetic viruses to give vaccine production a long-awaited speed boost."
"A central goal of synthetic biology is to achieve multi-signal integration and processing in living cells for diagnostic, therapeutic and biotechnology applications1. Digital logic has been used to build small-scale circuits, but other frameworks may be needed for efficient computation in the resource-limited environments of cells2, 3. Here we demonstrate that synthetic analog gene circuits can be engineered to execute sophisticated computational functions in living cells using just three transcription factors. Such synthetic analog gene circuits exploit feedback to implement logarithmically linear sensing, addition, ratiometric and power-law computations. The circuits exhibit Weber’s law behaviour as in natural biological systems4, operate over a wide dynamic range of up to four orders of magnitude and can be designed to have tunable transfer functions. Our circuits can be composed to implement higher-order functions that are well described by both intricate biochemical models and simple mathematical functions. By exploiting analog building-block functions that are already naturally present in cells3, 5, this approach efficiently implements arithmetic operations and complex functions in the logarithmic domain. Such circuits may lead to new applications for synthetic biology and biotechnology that require complex computations with limited parts, need wide-dynamic-range biosensing or would benefit from the fine control of gene expression." http://bit.ly/YWXbm2
"Advanced genetic engineering is already changing vaccine development and could make inroads into other branches of medicine.
Synthetic biology is breathing new life into the old-fashioned world of vaccine production, raising hopes that manufacturers could release vaccines much more quickly when outbreaks occur. At a meeting on synthetic biology held at MIT, the drug company Novartis said it has synthesized hybrid flu genomes in a process that could shave weeks off the time required to produce vaccines. When new flu strain emerges, government agencies normally send samples to vaccine manufacturers, who grow large numbers of the pathogen in chicken eggs as starting material for vaccines, says Philip Dormitzer, leader of viral vaccine research for Novartis. This process can take months and can miss the peak of an outbreak. But Novartis, working with synthetic biologists, has developed a way of chemically synthesizing virus genomes and growing them in tissue culture cells. That saves time and may produce more effective vaccines. The idea is to build a synthetic virus based on sequence data that can be distributed much more quickly than actual viral material harvested at the site of an outbreak. The synthetic viral genome combines a genomic backbone common to many flu viruses with genes specific to the strains seen in a new outbreak. In 2011, the team tested its method in response to a mock outbreak of a bird-flu virus (one closely related to the H7N9 virus currently spreading in China). Starting at 8 a.m. on Monday that year, the team began to chemically synthesize a viral genome based on sequence data, says Dormitzer. By noon the following Friday, the team had confirmed that it had live virus growing in cell culture......"
by Rainer Breitling , Fiona Achcar , and Eriko Takano
"The successful engineering of secondary metabolite production relies on the availability of detailed computational models of metabolism. In this brief review we discuss the types of models used for synthetic biology and their application for the engineering of metabolism. We then highlight some of the major modeling challenges, in particular the need to make informative model predictions based on incomplete and uncertain information. This issue is particularly pressing in the synthetic biology of secondary metabolism, due to the genetic diversity of microbial secondary metabolite producers, the difficulty of enzyme-kinetic characterization of the complex biosynthetic machinery, and the need for engineered pathways to function efficiently in heterologous hosts. We argue that an explicit quantitative consideration of the resulting uncertainty of metabolic models can lead to more informative predictions to guide the design of improved production hosts for bioactive secondary metabolites."
by Quoc-Thai Nguyena, Maria E. Merloa, Marnix H. Medemaa,, Andris Jankevicsb, Rainer Breitlingb, Eriko Takano
"Many microbial secondary metabolites are of high biotechnological value for medicine, agriculture, and the food industry. Bacterial genome mining has revealed numerous novel secondary metabolite biosynthetic gene clusters, which encode the potential to synthesize a large diversity of compounds that have never been observed before. The stimulation or “awakening” of this cryptic microbial secondary metabolism has naturally attracted the attention of synthetic microbiologists, who exploit recent advances in DNA sequencing and synthesis to achieve unprecedented control over metabolic pathways. One of the indispensable tools in the synthetic biology toolbox is metabolomics, the global quantification of small biomolecules. This review illustrates the pivotal role of metabolomics for the synthetic microbiology of secondary metabolism, including its crucial role in novel compound discovery in microbes, the examination of side products of engineered metabolic pathways, as well as the identification of major bottlenecks for the overproduction of compounds of interest, especially in combination with metabolic modeling. We conclude by highlighting remaining challenges and recent technological advances that will drive metabolomics towards fulfilling its potential as a cornerstone technology of synthetic microbiology."
"In May 2010, the J. Craig Venter Institute announced the creation of a simple bacterial cell entirely controlled by a chemically synthesized genome.1 The scientists started with the digital information of the organism’s genomic DNA sequence and chemically synthesized one nucleotide at a time, the full 1.08 million base pairs that made up the organisms genome.2 The synthetic genome was then inserted into a host bacterium that had its native DNA removed.3 The resulting man-made bacterium was able to replicate itself using only the synthetic genome.4 Advances in the ability to synthesize genome-length strands of DNA have coincided with a growing understanding of the functions of individual genes and gene networks.5 With the available knowledge of how whole genomes function and the technical capability of synthesizing whole genomes, it will be possible to digitally design novel organisms to perform some desired function and then manifest that synthetic organism in the real world.6 Creation of the first synthetic organism provided “a proof of principle for producing cells based on computer- designed genome sequences...."
On June 20, the White House will host a Champions of Change event to highlight outstanding individuals, organizations, or research projects promoting and using open scientific data and publications to accelerate progress and improve our world.
PLOS ONE: an inclusive, peer-reviewed, open-access resource from the PUBLIC LIBRARY OF SCIENCE. Reports of well-performed scientific studies from all disciplines freely available to the whole world.
Gerd Moe-Behrens's insight:
by Giuraniuc CV, Macpherson M, Saka Y.
"onstruction of synthetic genetic networks requires the assembly of DNA fragments encoding functional biological parts in a defined order. Yet this may become a time-consuming procedure. To address this technical bottleneck, we have created a series of Gateway shuttle vectors and an integration vector, which facilitate the assembly of artificial genes and their expression in the budding yeast Saccharomyces cerevisiae. Our method enables the rapid construction of an artificial gene from a promoter and an open reading frame (ORF) cassette by one-step recombination reaction in vitro. Furthermore, the plasmid thus created can readily be introduced into yeast cells to test the assembled gene's functionality. As flexible regulatory components of a synthetic genetic network, we also created new versions of the tetracycline-regulated transactivators tTA and rtTA by fusing them to the auxin-inducible degron (AID). Using our gene assembly approach, we made yeast expression vectors of these engineered transactivators, AIDtTA and AIDrtTA and then tested their functions in yeast. We showed that these factors can be regulated by doxycycline and degraded rapidly after addition of auxin to the medium. Taken together, the method for combinatorial gene assembly described here is versatile and would be a valuable tool for yeast synthetic biology." http://bit.ly/15Rc64b
Scientists have made stable colonies of embryonic stem cells by injecting the DNA from an adult human into a human egg cell emptied out of its genetic material (Scientists Make Human Stem Cells Through Cloning http://t.co/Jq0BNP6sKC...
Using analog computation circuits, MIT engineers design cells that can compute logarithms, divide and take square roots.
Gerd Moe-Behrens's insight:
by Anne Trafton
"MIT engineers have transformed bacterial cells into living calculators that can compute logarithms, divide, and take square roots, using three or fewer genetic parts.
Inspired by how analog electronic circuits function, the researchers created synthetic computation circuits by combining existing genetic “parts,” or engineered genes, in novel ways. The circuits perform those calculations in an analog fashion by exploiting natural biochemical functions that are already present in the cell rather than by reinventing them with digital logic, thus making them more efficient than the digital circuits pursued by most synthetic biologists, according to Rahul Sarpeshkar and Timothy Lu, the two senior authors on the paper, describing the circuits in the May 15 online edition of Nature. “In analog you compute on a continuous set of numbers, which means it’s not just black and white, it’s gray as well,” says Sarpeshkar, an associate professor of electrical engineering and computer science and the head of the Analog Circuits and Biological Systems group at MIT"
*Collecting synthetic biology – an iGEM of an idea*
by anonymous / Science Museum’
"Collecting stuff is generally the bit I like most about my job. That’s probably why I’ve got a bit over excited about the new acquisitions we’ve made related to synthetic biology – from no other than Tom Knight widely described as the “father” of the discipline.
Synthetic biology is research that combines biology and engineering. Sounds like genetic engineering by another name? Well yes, but it goes much further. It looks to create new biological functions not found in nature, designing them according to engineering principles. Some see the field as the ultimate achievement of knowledge, citing the engineer-mantra of American physicist Richard Feynman, “What I cannot create, I do not understand”...."
"Some enthusiasts of synthetic biology envision technologies that would “improve” humans—and, perhaps, create useful “subhumans.”
Synthetic biology is a collection of techniques, and research and busi- ness agendas, that includes the con- struction of DNA sequences that encode protein or RNA molecules which assemble into macromolecu- lar complexes, biochemical circuits and networks with known or novel functions; the substitution of chemi- cally synthesized DNA or DNA ana- logues for their natural counterparts in order to change cell behavior and/ or produce novel products; and at- tempts to define and construct basic living systems from minimal sets of molecules.1 Synthetic biology has been termed “extreme genetic engi- neering” by the Erosion Technology and Concentration (ETC) Group2, in contrast to earlier recombinant DNA techniques that sought mainly to modify and refine existing types of organisms by altering or inserting in- dividual genes...."
Realizing constructive applications of synthetic biology requires continued development of enabling technologies as well as policies and practices to ensure these technologies remain accessible for research. Broadly defined, enabling technologies for synthetic biology include any reagent or method that, alone or in combination with associated technologies, provides the means to generate any new research tool or application. Because applications of synthetic biology likely will embody multiple patented inventions, it will be important to create structures for managing intellectual property rights that best promote continued innovation. Monitoring the enabling technologies of synthetic biology will facilitate the systematic investigation of property rights coupled to these technologies and help shape policies and practices that impact the use, regulation, patenting, and licensing of these technologies.ResultsWe conducted a survey among a self-identifying community of practitioners engaged in synthetic biology research to obtain their opinions and experiences with technologies that support the engineering of biological systems. Technologies widely used and considered enabling by survey participants included public and private registries of biological parts, standard methods for physical assembly of DNA constructs, genomic databases, software tools for search, alignment, analysis, and editing of DNA sequences, and commercial services for DNA synthesis and sequencing. Standards and methods supporting measurement, functional composition, and data exchange were less widely used though still considered enabling by a subset of survey participants.ConclusionsThe set of enabling technologies compiled from this survey provide insight into the many and varied technologies that support innovation in synthetic biology. Many of these technologies are widely accessible for use, either by virtue of being in the public domain or through legal tools such as non-exclusive licensing. Access to some patent protected technologies is less clear and use of these technologies may be subject to restrictions imposed by material transfer agreements or other contract terms. We expect the technologies considered enabling for￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼￼synthetic biology to change as the field advances. By monitoring the enabling technologies of synthetic biology and addressing the policies and practices that impact their development and use, our hope is that the field will be better able to realize its full potential."
"Yaniv Erlich shows how research participants can be identified from 'anonymous' DNA..
Late at night, a video camera captures a man striding up to the locked door of the information-technology department of a major Israeli bank. At this hour, access can be granted only by a fingerprint reader — but instead of using the machine, the man pushes a button on the intercom to ring the receptionist's phone. As it rings, he holds his mobile phone up to the intercom and presses the number 8. The sound of the keypad tone is enough to unlock the door. As he opens it, the man looks back to the camera with a shrug: that was easy. Yaniv Erlich — the star of this 2006 video — considers this one of his favourite hacks. Technically a “penetration exercise” conducted to expose the bank's vulnerabilities, it was one of several projects that Erlich worked on during a two-year stint with a security firm based near Tel Aviv. Since then, the 33-year-old computational biologist has been bringing his hacker ethos to biology. Now at the Whitehead Institute for Biomedical Research in Cambridge, Massachusetts, he is using genome data in new ways, and in the process exposing vulnerabilities in databases that hold sensitive information on thousands of individuals around the world....."
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