Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition
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Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition
Research, development and production of antiviral treatments since perspectives evolutionary and synthetic Biology: Study of Systems and Mechanims of evolution viruses through bioinformatics tools for immunomodulation addressed of systems delivery with iRNAs, antivirals and celular signaling regulation.
Curated by Cesar Saldaña
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An adaptor from translational to transcriptional control enables predictable assembly of complex regulation

An adaptor from translational to transcriptional control enables predictable assembly of complex regulation | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Chang C Liu,Lei Qi,Julius B Lucks,Thomas H Segall-Shapiro,Denise Wang,Vivek K Mutalik& Adam P Arkin

 

Nature Methods9,1088–1094(2012)doi:10.1038/nmeth.2184

 

Abstract:

 

Bacterial regulators of transcriptional elongation are versatile units for building custom genetic switches, as they control the expression of both coding and noncoding RNAs, act on multigene operons and can be predictably tethered into higher-order regulatory functions (a property called composability). Yet the less versatile bacterial regulators of translational initiation are substantially easier to engineer. To bypass this tradeoff, we have developed an adaptor that converts regulators of translational initiation into regulators of transcriptional elongation in Escherichia coli. We applied this adaptor to the construction of several transcriptional attenuators and activators, including a small molecule–triggered attenuator and a group of five mutually orthogonal riboregulators that we assembled into NOR gates of two, three or four RNA inputs. Continued application of our adaptor should produce large collections of transcriptional regulators whose inherent composability can facilitate the predictable engineering of complex synthetic circuits.

 

http://www.nature.com/nmeth/journal/v9/n11/full/nmeth.2184.html?WT.ec_id=NMETH-201211

 


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In This Issue - ACS Synthetic Biology (ACS Publications)

In This Issue - ACS Synthetic Biology (ACS Publications) | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

*ACS Synthetic Biology*
September 21st

*Compartment Size and Multimeric Protein Synthesis*
All chemical reactions in the cell take place inside a compartment, whose volume is typically in the range of a micro- to femtoliter. While the volume of the compartment is a fundamental physical parameter in such reactions and can affect intracompartmental reaction kinetics, there have been few studies to elucidate the effects of changes in volume.

*Test Tube Synthesis of the Bacteriophage T7*
The bottom-up synthesis of living systems in the laboratory is a standing challenge to biology, chemistry, and physics. Although many experimental approaches to synthesize complex biological systems in vitro have been proposed, there has been no demonstration to date of natural genome-sized DNA programs being entirely replicated and expressed in vitro into a self-assembled functioning whole.

*Evolutionary Stability of a Refactored Phage Genome*
When engineering a genetic system, only those genetic elements whose functional properties are entirely known are used. This enables elements from diverse genetic backgrounds to be put together to create new pathways and functions.

*Unsaturated Lipidoids for Efficient Intracellular Gene Delivery*
Intracellular gene delivery or gene therapy has long been viewed as a method of treatment for genetic disease. However, there is a lack of safe and efficient gene delivery vehicles.

*Engineering Functional DNA Translocation*
The “portal connector” of bacteriophage viruses is a pore-like structure that allows for DNA translocation. The high specificity of this connector along with its well-defined structure makes it attractive for use as a DNA-nanopore in synthetic tools.

*Synthetic Biology to Explain Cellular Information Processing*
Appropriate responses to environmental signals are essential for the survival of all cells and organisms. These responses are regulated by cellular networks that process these environmental cues.

http://bit.ly/Unxym5


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Designer Virus Pioneer Sees a Revolution Ahead for Synthetic Biology

Designer Virus Pioneer Sees a Revolution Ahead for Synthetic Biology | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

When researchers synthesized the poliovirus from scratch 10 years ago, it was a major feat in the rapidly growing field of synthetic biology. For the first time, scientists had chemically stitched together bits of DNA to create a functional virus without the guidance of a biological template.

Now the virologist who led that team, Eckard Wimmer of Stony Brook University, continues to push the field by constructing designer viruses and, potentially, designer vaccines. New York Genome Center spoke with Wimmer recently about the future of synthetic biology.


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Preparing synthetic biology for the world

Preparing synthetic biology for the world | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or “living devices.” As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space?


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Gerd Moe-Behrens's curator insight, January 25, 2013 2:19 PM

by
Gerd H. G. Moe-Behrens, Rene Davis and Karmella A. Haynes

"Synthetic Biology promises low-cost, exponentially scalable products and global health solutions in the form of self-replicating organisms, or “living devices.” As these promises are realized, proof-of-concept systems will gradually migrate from tightly regulated laboratory or industrial environments into private spaces as, for instance, probiotic health products, food, and even do-it-yourself bioengineered systems. What additional steps, if any, should be taken before releasing engineered self-replicating organisms into a broader user space? In this review, we explain how studies of genetically modified organisms lay groundwork for the future landscape of biosafety. Early in the design process, biological engineers are anticipating potential hazards and developing innovative tools to mitigate risk. Here, we survey lessons learned, ongoing efforts to engineer intrinsic biocontainment, and how different stakeholders in synthetic biology can act to accomplish best practices for biosafety."

http://bit.ly/W8eV9J

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Frontiers | Synthetic Biology: Applying Engineering to Life Sciences to Develop Rationally Designed Biological Parts, Devices, and Systems | Frontiers in Synthetic Biology

Synthetic Biology: Applying Engineering to Life Sciences to Develop Rationally Designed Biological Parts, Devices, and Systems

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Pradosh Mitter's curator insight, August 6, 2015 4:09 PM

Civil Engineering Reference Manual for the PE Exam - By Michael R. Lindeburg PE:
http://uae.quantity-takeoff.com/news/civil-engineering-reference-manual-for-the-pe-exam.html

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HIV virus spread and evolution studied through computer modeling

HIV virus spread and evolution studied through computer modeling | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it
Researchers at Los Alamos National Laboratory are investigating the complex relationships between the spread of the HIV virus in a population (epidemiology) and the actual, rapid evolution of the virus (phylogenetics) within each patient's body.

 

We have developed novel ways of estimating epidemics dynamics such as who infected whom, and the true population incidence of infection versus mere diagnoses dates," said Thomas Leitner, principal investigator. "Obviously, knowledge about these things is important for public health monitoring, decision making and intervention campaigns, and further to forensic investigations."

 

The team models the uninfected population using traditional differential equations on the computer; this is done for computational speed, because an agent-based component is much more demanding. Once a person is infected, he/she becomes an "agent" in computer modeling terms, and the model starts following their behavior individually, as well as the viral HIV evolution within the person.

 

read original for more: http://medicalxpress.com/news/2013-11-hiv-virus-evolution.html


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Lego-Like Cloning Platform for Transforming Synthetic Biology

Lego-Like Cloning Platform for Transforming Synthetic Biology | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Scientists at Oxford Genetics have developed a range of synthetic DNA products that they believe will revolutionize the genetic research sector: the SnapFast.


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Genetic programs constructed from layered logic gates in single cells

Genetic programs constructed from layered logic gates in single cells | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Tae Seok Moon,Chunbo Lou,Alvin Tamsir,Brynne C. Stanton& Christopher A. Voigt

Nature491,249–253(08 November 2012)doi:10.1038/nature11516

Received02 February 2012Accepted15 August 2012Published online07 October 2012

 

Abstract:

Genetic programs function to integrate environmental sensors, implement signal processing algorithms and control expression dynamics1. These programs consist of integrated genetic circuits that individually implement operations ranging from digital logic to dynamic circuits and they have been used in various cellular engineering applications, including the implementation of process control in metabolic networks and the coordination of spatial differentiation in artificial tissues. A key limitation is that the circuits are based on biochemical interactions occurring in the confined volume of the cell, so the size of programs has been limited to a few circuits1, 7. Here we apply part mining and directed evolution to build a set of transcriptional AND gates in Escherichia coli. Each AND gate integrates two promoter inputs and controls one promoter output. This allows the gates to be layered by having the output promoter of an upstream circuit serve as the input promoter for a downstream circuit. Each gate consists of a transcription factor that requires a second chaperone protein to activate the output promoter. Multiple activator–chaperone pairs are identified from type III secretion pathways in different strains of bacteria. Directed evolution is applied to increase the dynamic range and orthogonality of the circuits. These gates are connected in different permutations to form programs, the largest of which is a 4-input AND gate that consists of 3 circuits that integrate 4 inducible systems, thus requiring 11 regulatory proteins. Measuring the performance of individual gates is sufficient to capture the behaviour of the complete program. Errors in the output due to delays (faults), a common problem for layered circuits, are not observed. This work demonstrates the successful layering of orthogonal logic gates, a design strategy that could enable the construction of large, integrated circuits in single cells.

 

http://www.nature.com/nature/journal/v491/n7423/full/nature11516.html

 

 


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Fluorescent fusion protein knockout mediated by anti-GFP nanobody - Nature Struct. Mol. Biology

Fluorescent fusion protein knockout mediated by anti-GFP nanobody - Nature Struct. Mol. Biology | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

http://www.nature.com/nsmb/journal/v19/n1/full/nsmb.2180.html

Caussinus et al (2012)

The use of genetic mutations to study protein functions in vivo is a central paradigm of modern biology. Recent advances in reverse genetics such as RNA interference and morpholinos are widely used to further apply this paradigm. Nevertheless, such systems act upstream of the proteic level, and protein depletion depends on the turnover rate of the existing target proteins. Here we present deGradFP, a genetically encoded method for direct and fast depletion of target green fluorescent protein (GFP) fusions in any eukaryotic genetic system. This method is universal because it relies on an evolutionarily highly conserved eukaryotic function, the ubiquitin pathway. It is traceable, because the GFP tag can be used to monitor the protein knockout. In many cases, it is a ready-to-use solution, as GFP protein-trap stock collections are being generated in Drosophila melanogaster and in Danio rerio.


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aamoros2's curator insight, June 24, 2014 12:39 PM

Proteínas fluorescentes.

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Factory of Life - Science News

Factory of Life - Science News | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Synthetic biology was born a little more than a decade ago, an offshoot of traditional genetic engineering but distinct in its ambitions, precision and mind-set.


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How to turn living cells into computers - Nature.com

How to turn living cells into computers - Nature.com | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Synthetic biologists have developed DNA modules that perform logic operations in living cells.


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An Infinity of Viruses

An Infinity of Viruses | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

When I talk about viruses, I have to struggle with big numbers. 

If you get sick with the flu, for example, every infected cell in your airway produces about 10,000 new viruses. The total number of flu viruses in your body can rise to 100 trillion within a few days. That’s over 10,000 times more viruses than people on Earth.

If there can be so many viruses in a single person, how many viruses are there in total on our planet? I’ve hunted around for a number, and the one I’ve seen most often is 1031. As in, 10000000000000000000000000000000. As in over 10 million times more viruses than there are stars in the universe. As in, if you were to stack one virus on top of another, you’d create a tower that would stretch beyond the moon, beyond the sun, beyond Alpha Centauri, out past the edge of the Milky Way, past neighboring galaxies, to reach a height of 200 million light years.


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jeje y 1000000 por cada litro de agua marina

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Ed Rybicki's curator insight, February 26, 2013 1:19 AM

Definitely a Virus Planet!

Chris Upton + helpers's comment, February 26, 2013 2:50 PM
Lets leave "infinity" to Toy Story and Physics!
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Synthetic gene circuits pump up cell signals

Synthetic gene circuits pump up cell signals | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it
(Phys.org) —Synthetic genetic circuitry created by researchers at Rice University is helping them see, for the first time, how to regulate cell mechanisms that degrade the misfolded proteins implicated in Parkinson's, Huntington's and other diseases.

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*DESIGNER VIRUS PIONEER SEES A REVOLUTION AHEAD FOR SYNTHETIC BIOLOGY*

By Crystal Gammon

"When researchers synthesized the poliovirus from scratch 10 years ago, it was a major feat in the rapidly growing field of synthetic biology. For the first time, scientists had chemically stitched together bits of DNA to create a functional virus without the guidance of a biological template.

Now the virologist who led that team, Eckard Wimmer of Stony Brook University, continues to push the field by constructing designer viruses and, potentially, designer vaccines. New York Genome Center spoke with Wimmer recently about the future of synthetic biology.

Q: What's the most important thing we can gain from designer viruses?

A: We’re developing pretty good candidates for new vaccines. Current vaccines, such as influenza, often don't work well in old folks, for example, so we’ve set out to make new ones.

With conventional molecular biology methods, you cannot make radically changed viral genomes. It’s very tedious. But when we work with computer scientists to synthesize a virus, we can think about making very large changes in the viral genome. We then model those changes to see what would work (and what wouldn’t) before synthesizing the vaccine candidates.

Q: How has computer science changed synthetic biology?

A: Our challenge is to design a virus that's attenuated enough it won’t cause disease, but is still recognized and acted upon by the immune system. We can now shorten this design part to almost an afternoon. The time from thinking about a new vaccine to getting it in a test tube is now less than five months. Classical methods took two to three years.

Q: What are the next big challenges in synthetic biology?...."
http://bit.ly/TdMOEK


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Synthetic Biology Open Language (SBOL)

"Synthetic Biology Open Language (SBOL) is a software standard for the electronic exchange of specifications and descriptions of genetic parts, devices, modules, systems, and engineered genomes.

For a general introduction and the motivation for SBOL, readers can go to the Get Started Page
To learn more about SBOL, follow one of the links below."

 


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Synthetic Biology: Implications and Uses

Synthetic Biology: Implications and Uses | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Has a nice chapter with SynBio resources:

"Synthetic Biology Resources http://www.istl.org/10-spring/internet1.html Provides links to various resources on the internet, including synthetic biology associations, centers of research, ethics, training and educational resources, and journals
Synthetic Biology.net http://www.syntheticbiology.net/index.aspx Portal for professionals in synthetic biology providing information on news, events, products, suppliers, etc., regarding synthetic biology
Synthetic Biology Project http://www.synbioproject.org/ Established as an initiative of the Foresight and Governance Program of Woodrow Wilson International Center for Scholars to foster informed public and policy discourse concerning the advancement of Synthetic Biology
BioBricks Foundation http://bbf.openwetware.org/ Encourages the development and responsible use of technologies based on BioBrick™ standard DNA parts to allow synthetic biologists to program living organisms in the same way a computer scientist can program a computer (see below)
Registry of Standard Biological Parts http://partsregistry.org/Main_Page A collection of genetic parts that can be mixed and matched to build synthetic biology devices and systems
SynBERC Synthetic Biology Engineering Research Center http://www.synberc.org/ Mission is to develop technologies to build biological components and assemble them into integrated systems to perform designed tasks, train engineers for biology, and educate the public on Synthetic Biology
BIOFAB http://www.biofab.org/ Biological design–build facility that aims to produce useful collections of standard biological parts available to academic and commercial users
JBEI Registry https://public.jbeir.org/ Also aims to provide standard DNA parts for Synthetic Biology
GeneDesign http://www.genedesign.org/ Set of web applications that provides public access to a nucleotide manipulation pipeline for Synthetic Biology
SynBioSS Designer http://synbioss.sourceforge.net/ Software suite for the generation, storage, retrieval, and quantitative simulation of synthetic biological networks"

 


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Evolutionarily Stable Attenuation by Genome Rearrangement in a Virus


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Gerd Moe-Behrens's curator insight, June 26, 2013 3:59 PM

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Cecchini N, Schmerer M, Molineux IJ, Springman R, Bull JJ.

"Live, attenuated viruses provide many of the most effective vaccines. For the better part of a century, the standard method of attenuation has been viral growth in novel environments, whereby the virus adapts to the new environment but incurs a reduced ability to grow in the original host. The downsides of this approach were that it produced haphazard results, and even when it achieved sufficient attenuation for vaccine production, the attenuated virus was prone to evolve back to high virulence. Using bacteriophage T7, we apply a synthetic biology approach for creating attenuated genomes and specifically study their evolutionary stability. Three different genome rearrangements are employed, and although some initial fitness recovery occurs, all exhibit greatly impaired abilities to recover wild-type fitness over a hundred or more generations. Different degrees of stable attenuation appear to be attainable by different rearrangements. Efforts to predict fitness recovery using the extensive background of T7 genetics and biochemistry were only sometimes successful. The use of genome rearrangement thus offers a practical mechanism of evolutionary stable viral attenuation, with some progress toward prediction."

http://1.usa.gov/18gCAfE

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Computer programs 'mutate' to outlast viruses

Computer programs 'mutate' to outlast viruses | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

The KISS concept—keep it simple, stupid—may work in many situations. However, when it comes to evolution, complexity appears to be the best strategy for longterm survival. Researchers pitted self-replicating computer programs against computer viruses in the domain of the Avida platform for digital evolution. The co-evolution of host and virus ultimately led to organisms with capabilities superior to those of organisms that evolved without battling the viruses, says Luis Zaman of Michigan State University’s BEACON Center for the Study of Evolution in Action.


“The organisms faced off against some pretty nasty viruses, ones that quickly overcame the easy ways of becoming resistant,” says Zaman, who’s now a postdoctoral researcher at the University of Washington.

“This left only more and more complex options for co-evolving hosts. We thought to ourselves, maybe the organisms that were more readily adaptable than the others, more evolvable, would be the ones left standing at the end of the experiments.” The team of scientists showed that the long-lasting hosts were indeed more evolvable. The results are detailed in a study published in PLOS Biology.


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Giant viruses coexisted with the cellular ance... [BMC Evol Biol. 2012] - PubMed - NCBI

Giant viruses coexisted with the cellular ance... [BMC Evol Biol. 2012] - PubMed - NCBI | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it
PubMed comprises more than 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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Genome-editing tools storm ahead : Nature Methods : Nature Publishing Group

Genome-editing tools storm ahead : Nature Methods : Nature Publishing Group | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it
The menu of maturing, diversifying methods calls for careful selections in experimental design.

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Fluorescent proteins and in vitro genetic organization for cell-free synthetic biology

Fluorescent proteins and in vitro genetic organization for cell-free synthetic biology | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

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Gerd Moe-Behrens's curator insight, March 9, 2013 1:57 PM

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Roberta Lentini , Michele Forlin , Laura Martini , Cristina Del Bianco , Amy C Spencer , Domenica Torino , and Sheref S Mansy

"To facilitate the construction of cell-free genetic devices, we evaluated the ability of 17 different fluorescent proteins to give easily detectable fluorescence signals in real-time from in vitro transcription-translation reactions with a minimal system consisting of T7 RNA polymerase and E. coli translation machinery, i.e. the PUREsystem. The data were used to construct a ratiometric fluorescence assay to quantify the effect of genetic organization on in vitro expression levels. Synthetic operons with varied spacing and sequence composition between two genes that coded for fluorescent proteins were then assembled. The resulting data indicated which restriction sites and where the restriction sites should be placed in order to build genetic devices in a manner that does not interfere with protein expression. Other simple design rules were identified, such as the spacing and sequence composition influences of regions upstream and downstream of ribosome binding sites and the ability of non-AUG start codons to function in vitro."

http://bit.ly/12DfUo5

see also
Cell-free synthetic biology: Thinking outside the cell http://bit.ly/YjBmWH
Fig taken from this ref.

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Discovery in synthetic biology a step closer to new industrial revolution - Imperial College London

Discovery in synthetic biology a step closer to new industrial revolution - Imperial College London | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it

Parts made up of DNA are re-engineered by scientists and put into cells to make biological factories. However, a major bottleneck in synthetic biology is the lack of parts from which to build new types of factories. To build parts using the current time-consuming method, scientists have to re-engineer DNA in a cell and observe how it works. If it functions according to their specifications, then the scientists store the part specifications in a catalogue.

 

Now, scientists from Imperial College London have devised a much quicker method that does away with the need for them to re-engineer a cell every time they want to make a new part. The team say their work could lead to vast new libraries of off-the-shelf components that could be used to build more sophisticated biological factories.


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US bird flu research to resume under new restrictions

US bird flu research to resume under new restrictions | Evolutionary and Synthetic Biology: Design devices for addressed antiviral inhibition | Scoop.it
Back in January 2012, the US government announced it was joining with scientists around the world and temporarily suspending research on the deadly pathogen H5N1, also known as avian flu or "bird...

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Ed Rybicki's curator insight, February 25, 2013 3:08 AM

" "the policy aims to preserve the benefits of life sciences research while minimizing the risk of misuse.""

 

OK - can't argue too hard with that, I suppose?  EXCEPT that it probably limits access to the research of countries where the virus is ACTUALLY a problem.