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Three-dimensional patterning of multiple cell populations through orthogonal genetic control of cell motility

Three-dimensional patterning of multiple cell populations through orthogonal genetic control of cell motility | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Mackay JL, Sood A, Kumar S.

"The ability to independently assemble multiple cell types within a three-dimensional matrix would be a powerful enabling tool for modeling and engineering complex tissues. Here we introduce a strategy to dynamically pattern distinct subpopulations of cells through genetic regulation of cell motility. We first describe glioma cell lines that were genetically engineered to stably express constitutively active or dominant negative Rac1 GTPase mutants under the control of either a doxycycline-inducible or cumate-inducible promoter. We culture each population as multicellular spheroids and show that by adding or withdrawing the appropriate inducer at specific times, we can control the timing and extent of Rac1-dependent cell migration into three-dimensional collagen matrices. We then report results with mixed spheroids in which one subpopulation of cells expresses dominant negative Rac1 under a doxycycline-inducible promoter and the other expresses dominant negative Rac1 under a cumate-inducible promoter. Using this system, we demonstrate that doxycycline and cumate addition suppress Rac1-dependent motility in a subpopulation-specific and temporally-controlled manner. This allows us to orthogonally control the motility of each subpopulation and spatially assemble the cells into radially symmetric three-dimensional patterns through the synchronized addition and removal of doxycycline and cumate. This synthetic biology-inspired strategy offers a novel means of spatially organizing multiple cell populations in conventional matrix scaffolds and complements the emerging suite of technologies that seek to pattern cells by engineering extracellular matrix properties."



 http://bit.ly/1e0zDC3

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Innovation regimes based on collaborative and global tinkering: Synthetic biology and nanotechnology in the hackerspaces

Innovation regimes based on collaborative and global tinkering: Synthetic biology and nanotechnology in the hackerspaces | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Denisa Kera


"Typically nanotechnology and synthetic biology are discussed in terms of novel life forms and materials created in laboratories, or by novel convergences of technologies (ICTs and biological protocols) and science paradigms (engineering and biology) they initiated. Equally inspiring is their ability to generate novel institutions and global communities around emergent sciences, which radicalize the forms of public engagement and ethical deliberation. We are starting to witness alternative (iGEM competitions) and almost underground R&D engagements with Synthetic Biology (DIYbio movement), which inspired the emerging bottom-up involvements in nanotechnologies in projects, such as the NanoSmanoLab in Slovenia. These bottom-up involvements use tinkering and design as models for both research and public engagement. They democratize science and initiate a type of grassroots “science diplomacy”, supporting research in developing countries. We will discuss several recent examples, which demonstrate these novel networks (“Gene gun” project by Rüdiger Trojok from the Copenhagen based hackerspace, Labitat.dk, the “Bioluminescence Project” by Patrik D'haeseleer from Biocurious biotech hackerspace in Sunnyvale, CA, and the “Biodesign for the real world” project by members of the Hackteria.org). They all use design prototypes to enable collaborative and global tinkering, in which science and community are brought together in open biology laboratories and DIYbio hackerspaces, such as Hackteria.org or Biocurious. In these projects research protocols encompass broader innovative, social and ethical norms. Hackerspaces represent a unique opportunity for a more inclusive, experimental, and participatory policy that supports both public and global involvements in emergent scientific fields."

 http://bit.ly/1aOnQ5p

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Andrew Hessel: Programming Living Things - The Next Generation Of Computing @ Compute Midwest 2013 - YouTube

Compute Midwest 2013: Andrew Hessel, Genomic Futurist @ Autodesk , Speaks About The Next Generation Of Computing: Programming Living Things. About Compute Mi...
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Is DIYbio the next big hacker movement?

Is DIYbio the next big hacker movement? | SynBioFromLeukipposInstitute | Scoop.it
“DIYbio” is the name given to the growing movement of people who are interested in performing science outside of traditional academic and corporate pharma.
Gerd Moe-Behrens's insight:

by
Kyrie Vala-Webb

"he group you hear tinkering away in your neighbor’s garage may be making molecules, not music. DIY biology, also known as “DIYbio” is the name given to the growing movement of people who are interested in performing science outside of traditional academic and corporate pharma environments.

Normative recently hosted Pantea Razzaghi, co-founder of Synbiota in our studio to talk to our team about synthetic biology and the role Synbiota is playing in the DIYbio movement. Synbiota is a platform that enables DIYbio makers to create virtual research institutes and radically reduce the barrier-to-entry for creating blockbuster life science products.
Based in Montreal and Toronto with users on all 7 continents, Synbiota recently won the Accelerator Innovative World Technology award at SXSW. At SxSW they also launched #ScienceHack, a research event in collaboration with Alberta-based Genomikon taking place March 28-30 in Haliburton, Ontario.

I spoke with Pantea while she was en route to Austin:
[KVW]: With this new context where science is being done how do you think it’s going to change the scientific process and the way we produce scientific knowledge?
[PR]: Mostly I think it’s going to have a big impact on making science accessible. I feel like people have very much had an impression of science that it’s extremely difficult to get involved. You’ll often hear a lot of people say I’m really interested in this but I didn’t do well in high school science and so it feels like it’s hard to access it, it’s hard to find a place where you can go to get started. So I think having these DIY movement and having specific public labs or citizen labs allow people physical spaces to get started. Y
One of the other things about bio: unlike getting involved in coding or other technical movements, it’s very much not only digital but also physical. You want to have your hands in a wet lab, and that’s quite intimidating and a little bit hard to get started. So having these DIYbio spaces in physical places actually gives people an opportunity to get their hands literally wet and reduce that level of intimidation and offer them more of an opportunity to hop in and start getting involved.
[KWV]: One of the things we think a lot about at Normative is the future of our creations once they leave our hands and go out and live in the world and evolve. We think it’s important to think about the consequences of the things that we are creating – positive or negative, intended or unintended. I’m wondering if you can speak to what you think the potential outcomes of DIY are in the next 5 years, both positively and negatively.
[PR]: The great thing about the DIYbio movement at least in the States and Europe is that it is happening in visible places. One of the issues people have had with hacker movements that started in virtual spaces is that they could really keep incognito and remain more invisible.
With the DIYbio movement – public labs like La Paillasse, BioCurious, GenSpace – these spaces are physical spaces; they are registered, they have addresses and entities so it makes it easier and more accessible for governments and society to stay informed of activity. Their involvement is less about monitoring and more about participation and collaboration. So this again helps reduce the possibility of things skewing to a potentially more negative side.
I think as with all technology there’s potential for any different applications to be made. For this reason I think it’s important to focus on conversation, people talking about things, people sharing content, people having a place to go where they can speak about what they’re working on and therefore have visibility of their projects.
[KWV]: Can you share your thoughts on what you think the role is for designers in the world of DIYbio?
[PR] Sure! For designers I think it’s a great opportunity for them to add a new kind of paint to their palette. This is another extension to our toolkit of materials and methods that we can use to produce useful applications when solving complex problems.
[KWV]: Are there specific challenges in communicating between designers and scientists that are trends or things that come up often?
[PR]: If you think of experiments as recipes, I think scientists are very concerned about how you put the ingredients together, what the ingredients are, the measurements that go into that recipe – did it produce the outcome first hypothesized? While designers are more interested in explaining the historical context of the recipe, to talk about how it tastes, its textures, if they were lucky enough to have unexpected results.
So these are some of the variances I’ve noticed, and why there’s such great potential in bringing designers and scientists together to help each other out. Each has a different approach, and together they are more whole and able to inspire one another...."

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Quantum Biology: Better Living Through Quantum Mechanics - The Nature of Reality

Quantum Biology: Better Living Through Quantum Mechanics - The Nature of Reality | SynBioFromLeukipposInstitute | Scoop.it
A quantum computer is a serious piece of hardware. My colleagues and I build quantum computers from superconducting systems, quantum dots, lasers operating on nonlinear crystals,... Read Full Postelse
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From dead leaf, to new life: TAL effectors as tools for synthetic biology

Gerd Moe-Behrens's insight:

by
Orlando de Lange, Andreas Binder, Thomas Lahaye

"Whether rice, yeast, or fly there is barely a model organism not yet reached by transcription activator like effectors (TALEs) and their derivative fusion proteins. Insights into fundamental biology are now arriving on the back of work in the last years to develop these proteins as tools for molecular biology. This began with the publication of the simple cipher determining base-specific DNA recognition by TALEs in 2009 and now encompasses a huge variety of established fusion proteins mediating targeted modifications to transcriptome, genome, and recently, epigenome. Straightforward design and exquisite specificity, allowing unique sites to be targeted even within complex eukaryote genomes, are key to the popularity of this system. Synthetic biology is one field that is just beginning to make use of these properties with a number of recent publications demonstrating TALE-mediated regulation of synthetic genetic circuits. Intense interest has surrounded the CRISPR/Cas9 system within the last twelve months and it is already proving its mettle as a tool for targeted gene modifications and transcriptional regulation. However, questions over off-target activity and means for independent regulation of multiple Cas9-guide RNA pairs will have to be resolved before this method enters into the synthetic biology toolbox. TALEs are already showing promise as regulators of synthetic biological systems, a role that will likely be developed further in the coming years."


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Drug Delivery by Tattooing to Treat Cutaneous Leishmaniasis

Drug Delivery by Tattooing to Treat Cutaneous Leishmaniasis | SynBioFromLeukipposInstitute | Scoop.it
This study establishes a proof-of-concept that a tattoo device can target intra-dermal drug delivery against cutaneous leishmaniasis (CL). The selected drug is oleylphosphocholine (OlPC) formulated as liposomes, particles known to be prone to macrophage ingestion. We first show that treatment of cultured Leishmania-infected macrophages with OlPC-liposomes results in a direct dose-dependent killing of intracellular parasites. Based on this, in vivo efficacy is demonstrated using a 10 day tattooing-mediated treatment in mice infected with L. major and L. mexicana. In both models this regimen results in rapid clinical recovery with complete regression of skin lesions by Day 28. Parasite counts and histopathology examination confirm high treatment efficacy at the parasitic level. Low amount of drug required for tattooing combined with fast clinical recovery may have a positive impact on CL patient management. This first example of tattoo-mediated drug delivery could open to new therapeutic interventions in the treatment of skin diseases.
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Synthetic Aesthetics: Investigating Synthetic Biology’s Designs on Nature

Synthetic Aesthetics: Investigating Synthetic Biology’s Designs on Nature | SynBioFromLeukipposInstitute | Scoop.it
*This forthcoming tome looks like it oughta be pretty happening. *It's a press release. *******************************************************************
Gerd Moe-Behrens's insight:

by
Bruce Sterling

"Synthetic Aesthetics

Investigating Synthetic Biology’s Designs on Nature
By Alexandra Daisy Ginsberg, Jane Calvert, Pablo Schyfter, Alistair Elfick, and Drew Endy
Publication date: March 31, 2014
Synthetic biology manipulates the stuff of life. For synthetic biologists, living matter is programmable material. In search of carbon-neutral fuels, sustainable manufacturing techniques, and innovative drugs, these researchers aim to redesign existing organisms and even construct completely novel biological entities. Some synthetic biologists see themselves as designers, inventing new products and applications. But if biology is viewed as a malleable, engineerable, designable medium, what is the role of design and how will its values apply?
In this book, synthetic biologists, artists, designers, and social scientists investigate synthetic biology and design. After chapters that introduce the science and set the terms of the discussion, the book follows six boundary-crossing collaborations between artists and designers and synthetic biologists from around the world, helping us understand what it might mean to ‘design nature.’ These collaborations have resulted in biological computers that calculate form; speculative packaging that builds its own contents; algae that feeds on circuit boards; and a sampling of human cheeses. They raise intriguing questions about the scientific process, the delegation of creativity, our relationship to designed matter, and, the importance of critical engagement. Should these projects be considered art, design, synthetic biology, or something else altogether?
Synthetic biology is driven by its potential; some of these projects are fictions, beyond the current capabilities of the technology. Yet even as fictions, they help illuminate, question, and even shape the future of the field."

 http://wrd.cm/1fkByOa

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Material ecologies for synthetic biology: Biomineralization and the state space of design

Material ecologies for synthetic biology: Biomineralization and the state space of design | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Martyn Dade-Robertsona,  Carolina Ramirez Figueroaa, Meng Zhang

"This paper discusses the role that material ecologies might have in the emerging engineering paradigm of Synthetic Biology (hereafter SB). In this paper we suggest that, as a result of the paradigm of SB, a new way of considering the relationship between computation and material forms is needed, where computation is embedded into the material elements themselves through genetic programming. The paper discusses current trends to conceptualize SB in traditional engineering terms and contrast this from design speculations in terms of bottom up processes of emergence and self organization. The paper suggests that, to reconcile these positions, it is necessary to think about the design of new material systems derived from engineering living organisms in terms of a state space of production. The paper analyses this state space using the example of biomineralization, with illustrations from simple experiments on bacteria induced calcium carbonate. The paper suggests a framework involving three interconnected state spaces defined as: cellular (the control of structures within the cell structures within a cell, and specifically DNA and its expression through the process of transcription and translation); chemical (considered to occur outside the cell, but in direct chemical interaction with the interior of the cell itself); physical (which constitutes the physical forces and energy within the environment). We also illustrate, in broad terms, how such spaces are interconnected. Finally the paper will conclude by suggesting how a material ecologies approach might feature in the future development of SB."

 http://bit.ly/PkQNl6

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How to Make a Microscope Out of Paper in 10 Minutes

How to Make a Microscope Out of Paper in 10 Minutes | SynBioFromLeukipposInstitute | Scoop.it
A new microscope can be printed on a flat piece of paper and assembled in less than 10 minutes. And the parts to make it cost less than a dollar.
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Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV — NEJM

Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV — NEJM | SynBioFromLeukipposInstitute | Scoop.it
Original Article from The New England Journal of Medicine — Gene Editing of CCR5 in Autologous CD4 T Cells of Persons Infected with HIV
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Harvard professor Sophia Roosth examines how synthetic biology is remaking life

Harvard professor Sophia Roosth examines how synthetic biology is remaking life | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

*Biological Time Travel*

"FROM GLOWING FISH to bacteria that can count, synthetic biologists are now able to create life forms never before seen on earth. “Historians and Ecclesiastes be damned,” says Sophia Roosth, assistant professor in the history of science. “In the first decades of the twenty-first century, a number of things are new under the sun.”

In a lecture last Wednesday drawn from her forthcoming book, Synthetic: How Life Got Made, Roosth, a Joy Foundation Fellow this year at the Radcliffe Institute for Advanced Study, described her analysis of recent attempts at “de-extinction,” the effort to recreate extinct or endangered species using modern technologies. In 2003, scientists employing a technique similar to that used to create Dolly the sheep were able, if only temporarily, to resurrect the extinct bucardo, or Pyrenean ibex, by inserting its DNA into the eggs of its closest living relatives—goats—and then implanting the resulting embryos in the wombs of 57 goats. (The only clone born alive died minutes after birth.) “Participating researchers treat these biotechnologies…as forms of biological time travel that weave past, present, and future,” Roosth said.
Other de-extinction efforts take a different approach, she noted. Although some scientists are working to resurrect the passenger pigeon through cloning, for example, others have focused on breeding and genetically modifying rock pigeons to exhibit passenger-pigeon-like traits. The second approach, said Roosth, brings up the complex question of what biologists consider a species. “For de-extinction scientists, purity of phenotype—things like morphology and behavior—trumps genetic equivalence or continuous lineage,” she explained. “An animal that looks and flocks like a passenger pigeon is a passenger pigeon, even if it harbors rock pigeon DNA.”
Roosth ended by describing Pleistocene Park, a nature reserve in Siberia where scientists are working to restore the steppe ecosystem characteristic of the last Ice Age. Current efforts focus on reintroducing large herbivores like musk oxen, bison, and moose, and, eventually, their predators, such as wolves and bears. The park hopes to become home one day to resurrected woolly mammoths as well. Roosth quoted Winthrop professor of genetics George Church, a leader of the mammoth de-extinction effort, who wrote in his book Regenesis: How Synthetic Biology Will Reinvent Nature and Ourselves, “It would be the closest thing to time travel: a return to the flora and fauna of the Pleistocene epoch, a sort of latter-day Siberian Eden.”
Ironically, there is nothing natural about the reconstructed wilderness, Roosth points out. Appearance and verisimilitude, the hallmarks of a resurrected passenger pigeon, become the defining characteristics of an entire ecosystem. “[These] interventions seek to produce wholly synthetic creatures that will stand in, counterintuitively, as semblances of untouched nature,” she declared, “a latter-day Garden of Eden seemingly unsullied by human hands, albeit generated by the most recent bioengineering techniques.”
..."


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Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells

Cell-autonomous correction of ring chromosomes in human induced pluripotent stem cells | SynBioFromLeukipposInstitute | Scoop.it
Ring chromosomes are structural aberrations commonly associated with birth defects, mental disabilities and growth retardation. Rings form after fusion of the long and short arms of a chromosome, and are sometimes associated with large terminal deletions. Owing to the severity of these large aberrations that can affect multiple contiguous genes, no possible therapeutic strategies for ring chromosome disorders have been proposed. During cell division, ring chromosomes can exhibit unstable behaviour leading to continuous production of aneuploid progeny with low viability and high cellular death rate. The overall consequences of this chromosomal instability have been largely unexplored in experimental model systems. Here we generated human induced pluripotent stem cells (iPSCs) from patient fibroblasts containing ring chromosomes with large deletions and found that reprogrammed cells lost the abnormal chromosome and duplicated the wild-type homologue through the compensatory uniparental disomy (UPD) mechanism. The karyotypically normal iPSCs with isodisomy for the corrected chromosome outgrew co-existing aneuploid populations, enabling rapid and efficient isolation of patient-derived iPSCs devoid of the original chromosomal aberration. Our results suggest a fundamentally different function for cellular reprogramming as a means of /`chromosome therapy/' to reverse combined loss-of-function across many genes in cells with large-scale aberrations involving ring structures. In addition, our work provides an experimentally tractable human cellular system for studying mechanisms of chromosomal number control, which is of critical relevance to human development and disease.
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Self-assembling nanocages are the largest standalone 3-D DNA structures yet

Self-assembling nanocages are the largest standalone 3-D DNA structures yet | SynBioFromLeukipposInstitute | Scoop.it
Move over, nanotechnologists, and make room for the biggest of the small. Scientists at the Harvard's Wyss Institute have built a set of self-assembling DNA cages one-tenth as wide as a bacterium. The structures are some of the largest and most complex structures ever constructed solely from DNA, they ...
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Genetic languages guide the design of synthetic biological systems

Genetic languages guide the design of synthetic biological systems | SynBioFromLeukipposInstitute | Scoop.it
(Phys.org) —Researchers at Virginia Tech and the Massachusetts Institute of Technology have used a computer-aided design tool to create genetic languages to guide the design of biological systems.
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iPhylo: Displaying a million DNA barcodes on Google Maps using CouchDB

iPhylo: Displaying a million DNA barcodes on Google Maps using CouchDB | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Roderic D. M. Page

"Following on from the previous post on putting GBIF data onto Google Maps, I'm now going to put DNA barcodes onto Google Maps. You can see the result at http://iphylo.org/~rpage/bold-map/, which displays around 1.2 million barcodes obtained from the International Barcode of Life Project (iBOL) releases. Let me describe how I made it.....

.....

function(doc) {
  var tile_size = 256;
  var pixels = 4;
  if (doc.lat && doc.lon) {
    for (var zoom = 0; zoom < 7; zoom++) {
  
    var x_pos = (parseFloat(doc.lon) + 180)/360 
      * Math.pow(2, zoom);
    var x = Math.floor(x_pos);
    
    var relative_x = Math.round(tile_size * (x_pos - x));
  
    var y_pos = (1-Math.log(Math.tan(parseFloat (doc.lat) 
      * Math.PI/180) + 1/Math.cos(parseFloat(doc.lat) 
      * Math.PI/180))/Math.PI)/2 
      * Math.pow(2,zoom);
    var y = Math.floor(y_pos);
    var relative_y = Math.round(tile_size * (y_pos - y));
  
    relative_x = Math.floor(relative_x / pixels) * pixels;
      relative_y = Math.floor(relative_y / pixels) * pixels;
  
    var tile = [];
    tile.push(zoom);
    tile.push(x);
    tile.push(y);
    tile.push(relative_x);
    tile.push(relative_y);
     
    emit(tile, 1);
    }
  }
}

.....
"


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Synthetic Biology: The Next Frontier in Chiral Chemistry for API Synthesis

Synthetic Biology: The Next Frontier in Chiral Chemistry for API Synthesis | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Cynthia Challener,

"The complexity of both small-molecule and large-molecule drugs is increasing as pharmaceutical companies seek therapeutics with new mechanisms of action. In small-molecule therapeutics, increasing complexity often translates to larger numbers of stereocenters. Because only the isomer of a chiral drug that exhibits activity must be produced in high purity, much effort has been invested over the past 20 to 30 years in the development of tools for the asymmetric synthesis of pharmaceutical intermediates. Classical resolution and other methods for the separation of isomers, including large-scale chiral chromatography, and advanced chemocatalysts that mediate a wide variety of enantioselective transformations and enable more rapid and efficient synthesis of complex pharmaceutical intermediates and APIs are widely used today. More recently, technology for the development and commercialization of a diverse array of enzymes that can catalyze stereoselective reactions has led to their increasing use for pharmaceutical synthesis. While advances continue to be made in chemocatalysis, the area of chiral chemistry generating the most excitement is synthetic biology, or the use of multiple enzymes in one-pot reactions (and ultimately in a single organism) to carry out sequential reactions that result in the production of an advanced intermediate or even an API.

While there haven’t been any major new breakthrough chemical or biological transformations reported in recent years, there continue to be incremental improvements in existing technologies. For the pharmaceutical industry, these advancements include improvements in processing capabilities, such as flow chemistry, that make large-scale implementation of these technologies possible, according to John Caldwell, editor-in-chief of Chirality and professor emeritus at the University of Liverpool. He also notes that the development of effective chiral transformations that are “greener” and proceed at large scale in water, use low levels of catalysts that can be recycled, require lower temperatures and pressures, reduce the number of steps through carefully designed cascade sequences, are more atom economical, and use less hazardous materials has become important in the pharmaceutical industry. “We now have a lot of choices of methods for obtaining pharmaceutical intermediates with extremely high enantioselectivities in the range of 99.9%, and part of the challenge now is choosing the best method for a given API,” he notes.
Route development based on good process chemistry is in fact crucial and should be addressed prior to choosing a chiral technology, according to Garrett Hoge, chiral technology manager at the ChiroTech Technology Center, part of Dr. Reddy’s Custom Pharmaceutical Services business. “It is important not to use chiral technology just for the sake of it. Chiral chemistry must be implemented in an effective manner. It is as important to have an efficient route to the prochiral substrate as it is to have a highly effective chiral catalyst,”  Hoge says.
“Greening” of chiral chemistry
The “greening” of chemical manufacturing is one trend that has led to the growing use of biocatalysts for asymmetric synthesis, because these reactions often proceed in water under mild conditions, produce less waste, and are highly selective. Biocatalysis has also passed the proof-of-concept stage, according to Hoge. In addition, Tom Moody, head of biocatalysis and isotope chemistry with Almac and a professor of chemistry at the University of Belfast, notes that a diverse array of enzymes are now commercially available in quantities suitable for pharmaceutical manufacturing. There are a large number of transaminases and dehydrogenases, for example, available for commercial-scale use that enable the enantioselective production of key building blocks and intermediates needed for API synthesis, according to Stefan Mix, Almac’s biocatalysis team leader.
Advances in molecular engineering 
The increased availability of enzymes can be traced back to significant advances that have been achieved in molecular biology, metabolic engineering, and bioinformatics, according to Moody. “The design and engineering of enzymes for highly selective chiral transformations is now possible under tight timelines,” Mix notes. “In fact, a customized enzyme for a specific application can be developed in a few months rather than with extended periods of time and cost,” Mix explains. In many cases today, the cost of chiral ligands is greater than the cost of the enzyme that can provide the same product,” he adds. Hoge also points out that the identification of the gene of interest within a specific organism is also much easier today, and genes can be synthesized for just s few $100.
Access to enzymes
The availability of large quantities of enzymes at reasonable cost, combined with the greater sustainability of processes based on biocatalysts, has led to their use at earlier stages of the drug development process. “There is definitely a growing acceptance of the use of enzymes for the synthesis of APIs according to GMP,” Moody says. However, unlike for chemocatalysis, for which there are established procedures and guidelines for GMP manufacturing, a scientific approach has been undertaken for biocatalysis. Selected industrial specialists are now getting together to prepare a detailed document for the application of enzymes under GMP that will be published in 2014, he notes. Mix adds that, even though medicinal chemists are slow to adopt novel technologies, where once it was common to use enzyme catalysis only in second-generation synthetic routes, today biocatalysts are being considered from the earliest phases of new product development because of the benefits they provide in terms of cost, productivity, and efficiency.
One leading example of the implementation of a second-generation biocatalytic route was achieved by Merck & Co. A highly active and stable immobilized transaminase catalyst for the reduction of ketones to chiral amines created using directed evolution techniques served as a replacement for a rhodium-catalyst used for asymmetric enamine hydrogenation in the production of the antidiabetic drug Januvia (sitagliptin) (1). Development of the enzyme was accomplished in 10 months through cooperation with Codexis. The process demonstrated the potential to improve productivity by 56%, increase yield by 10-13%, and reduce overall waste generation by 19%, according to Merck. A pilot plant process was completed in 2009, and FDA granted approval for the new route in April 2012 (2).
The work that Frances Arnold, the Dick and Barbara Dickinson professor of chemical engineering, bioengineering, and biochemistry at the California Institute of Technology, demonstrates the versatility and potential of enzyme catalysis. Arnold has engineered a bacterial cytochrome P450 enzyme to catalyze highly diastereo and enantioselective carbene transfers from diazoester reagents to aryl-substituted olefins, enabling cyclopropanation through a route not observed in nature (3).
Gaining acceptability
More recently, the idea of synthetic biology has taken hold, according to all three scientists. “Pharmaceutical companies, contract manufacturers, and academic researchers are all investigating the possibility of engineering systems that consist of multiple enzymes that work in tandem and/or in sequence to generate complex chiral molecules with high selectivity,” Hoge explains. Further down the road, Moody says the ultimate goal is to engineer whole cells that switch on and off genes for different enzymes and can take basic raw materials and convert them into isomerically pure, complex, highly value added pharmaceutical intermediates, and ideally APIs themselves. “Investigations are still at the very early stages, but the interest in biomimetic synthesis is very high, and there is a wealth of transformations possible given the biological complexity of nature,” Mix observes.
ChiroTech, for example, has developed a two-enzyme system for the dynamic kinetic resolution of nonnatural α-amino acids. The company engineered N-acetyl amino acid racemase (NAAAR) to catalyze the racemization of many N-Acetyl amino acids, which when used in combination with an L- or D- acylase enzyme, enables their dynamic kinetic resolution. “Because the NAAAR enzyme is general in its ability to racemize many N-Acyl amino acids, we have found many applications for this system and typically achieve an enantiomeric purity of 99%,” Hoge comments.
Don’t count out chemocatalysis
Chemocatalysts will always have a place in API manufacturing, even though much of the excitement today is centered around biocatalysis. “Asymmetric hydrogenation in particular is a very important reaction in the pharmaceutical industry and will continue to be so,” Hoge asserts. He adds that there are still many new applications yet to be discovered. The fact that many chiral ligands are coming off patent will also promote the use of chemocatalysis because the cost of catalyst systems will decline significantly. In addition, chemocatalysts are very attractive for generics manufacturers, who can capitalize on asymmetric hydrogenation technology by improving on innovator routes that might not access a chiral technology. “These new and improved routes are enabled with technology allowing for more efficient implementation and a lower cost of goods than the originals,” Hoge notes.
Cascade organocatalysis
Organocatalysts also show potential for use in chiral transformations, particularly when used in cascade reactions, such as those being developed by David MacMillan, the James S. McDonnell distinguished university professor of chemistry at Princeton University. “We have a much greater understanding of the molecular environment required for catalysts, and therefore there is greater potential to design effective organocatalysts,” Caldwell says. In fact, ChiroTech has found that industrial application of this technology is possible and plans to bring an organocatalytic route to the plant within the next several months, according to Hoge.
Fitting the theme of synthetic biology, MacMillan’s approach to organocascade catalysis is based on the biochemical blueprints of biosynthesis. According to MacMillan, it includes the successful merger of different reactivity platforms, allowing access to intricate structural motifs directly applicable to natural product synthesis and enabling the straightforward generation of multiple stereocenters in a single operation. His group is using this strategy to construct the chiral frameworks of several complex natural products. Most recently, they achieved the enantioselective total synthesis of (−)-minovincine in nine chemical steps (4).
Caldwell believes that the design of cascade reactions through the assembly of known chemistry--whether involving organo-, chemo-, or biocatalysis--in unique sequences that leverage the best properties of each provides tremendous opportunities for advancing asymmetric synthesis in general and developing practical, efficient, and more sustainable commercial-scale routes to enantiomerically pure pharmaceutical intermediates and APIs."


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TeselaGen Is Building A Platform For Rapid Prototyping in Synthetic Biology | TechCrunch

TeselaGen Is Building A Platform For Rapid Prototyping in Synthetic Biology | TechCrunch | SynBioFromLeukipposInstitute | Scoop.it
As the costs of DNA sequencing and synthesis drop precipitously, a host of computer science-meets-biotech startups are cropping up in Silicon Valley...
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Tattoos that Cure Disease

Tattoos that Cure Disease | SynBioFromLeukipposInstitute | Scoop.it
A tattoo may make a statement, but can it also help fight disease? Find out...
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Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals

Characterizing bacterial gene circuit dynamics with optically programmed gene expression signals | SynBioFromLeukipposInstitute | Scoop.it
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Evan J Olson, Lucas A Hartsough, Brian P Landry, Raghav Shroff & Jeffrey J Tabor
"Gene circuits are dynamical systems that regulate cellular behaviors, often using protein signals as inputs and outputs. Here we have developed an optogenetic 'function generator' method for programming tailor-made gene expression signals in live bacterial cells. We designed precomputed light sequences based on experimentally calibrated mathematical models of light-switchable two-component systems and used them to drive intracellular protein levels to match user-defined reference time courses. We used this approach to generate accelerated and linearized dynamics, sinusoidal oscillations with desired amplitudes and periods, and a complex waveform, all with unprecedented accuracy and precision. We also combined the function generator with a dual fluorescent protein reporter system, analogous to a dual-channel oscilloscope, to reveal that a synthetic repressible promoter linearly transforms repressor signals with an approximate 7-min delay. Our approach will enable a new generation of dynamical analyses of synthetic and natural gene circuits, providing an essential step toward the predictive design and rigorous understanding of biological systems."
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*Rice synthetic biologists shine light on genetic circuit analysis*
by
Jade Boyd
"Bioengineers invent ‘light tube array,’ ‘bioscilloscope’ to test, debug genetic circuits
In a significant advance for the growing field of synthetic biology, Rice University bioengineers have created a toolkit of genes and hardware that uses colored lights and engineered bacteria to bring both mathematical predictability and cut-and-paste simplicity to the world of genetic circuit design.
“Life is controlled by DNA-based circuits, and these are similar to the circuits found in electronic devices like smartphones and computers,” said Rice bioengineer Jeffrey Tabor, the lead researcher on the project. “A major difference is that electrical engineers measure the signals flowing into and out of electronic circuits as voltage, whereas bioengineers measure genetic circuit signals as genes turning on and off.”
In a new paper appearing online today in the journal Nature Methods, Tabor and colleagues, including graduate student and lead author Evan Olson, describe a new, ultra high-precision method for creating and measuring gene expression signals in bacteria by combining light-sensing proteins from photosynthetic algae with a simple array of red and green LED lights and standard fluorescent reporter genes. By varying the timing and intensity of the lights, the researchers were able to control exactly when and how much different genes were expressed.
“Light provides us a powerful new method for reliably measuring genetic circuit activity,” said Tabor, an assistant professor of bioengineering who also teaches in Rice’s Ph.D. program in systems, synthetic and physical biology. “Our work was inspired by the methods that are used to study electronic circuits. Electrical engineers have tools like oscilloscopes and function generators that allow them to measure how voltage signals flow through electrical circuits. Those measurements are essential for making multiple circuits work together properly, so that more complex devices can be built. We have used our light-based tools as a biological function generator and oscilloscope in order to similarly analyze genetic circuits.”
...."
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"Post-Myriad Genetics Copyright of Synthetic Biology and Living Media" by Michael D. Murray

"Post-Myriad Genetics Copyright of Synthetic Biology and Living Media" by Michael D. Murray | SynBioFromLeukipposInstitute | Scoop.it
This Article addresses copyright as a viable form of intellectual property protection for living, organic creations of science and art. The United States Supreme Court’s decision in Association for Molecular Pathology v. Myriad Genetics, Inc.[1] narrowed patent-eligible protection over living components of humans or other organisms. Synthetic biologists are expected to look with renewed focus on copyright law for the intellectual property protection of biological creations. The contribution of this Article is to reveal that the same issues are raised with regard to the copyrightability of the works of synthetic biology as are raised by pictorial, graphic, and sculptural arts that use and produce living media as their works. The current contours of copyrightability present four identical questions that are particularly relevant to and difficult to answer in the context of science and art that purports to create works of living media:
Is living media copyrightable subject matter?
What is authorship (or who is an author) of living media?
What does it mean to create a fixed and tangible work of living media?
What constitutes an original creation of living media under the originality doctrines of merger and scenes a faire?
This Article will provide an analytical framework for rethinking the contours of copyright so as to answer these questions by comparing contemporary scientific methods of creation with artistic methods in order to determine the copyright narratives and metaphors of subject matter, authorship, creation, and originality that best address the concerns underlying these four questions and allow copyright protection over the works.
[1] Association for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107 (Jun. 13, 2013) (isolated DNA sequences not patentable).
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Chemical synthetic biology

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Chiarabelli, Cristiano; Luisi, Pier Luigi

"Although both the most popular form of synthetic biology (SB) and chemical synthetic biology (CSB) share the biotechnologically useful aim of making new forms of life, SB does so by using genetic manipulation of extant microorganism, while CSB utilises classic chemical procedures in order to obtain biological structures which are non-existent in nature. The main query concerning CSB is the philosophical question: why did nature do this, and not that? The idea then is to synthesise alternative structures in order to understand why nature operated in such a particular way. We briefly present here some various examples of CSB, including those cases of nucleic acids synthesised with pyranose instead of ribose, and proteins with a reduced alphabet of amino acids; also we report the developing research on the “never born proteins” (NBP) and “never born RNA” (NBRNA), up to the minimal cell project, where the issue is the preparation of semi-synthetic cells that can perform the basic functions of biological cells."

 http://bit.ly/1crgtqj

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Why Synthetic Biology Is the Field of the Future

Why Synthetic Biology Is the Field of the Future | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

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Jay Keasling 

"Most Americans may not be familiar with synthetic biology, but they may come to appreciate its advances someday soon. Synthetic biology focuses on creating technologies for designing and building biological organisms. A multidisciplinary effort, it calls biologists, engineers, software developers, and others to collaborate on finding ways to understand how genetic parts work together, and then to combine them to produce useful applications.

Synthetic biology is a relatively young field, begun only about ten years ago. But in that time, we have made some astonishing progress. This is due, in part, to the enormous improvements in our ability to synthesize and sequence DNA. But we’ve also gained a much greater understanding of how the various parts of the genome interact. We now can reliably combine various genetic pieces to produce a range of consumer products, from biofuels to cosmetics.

In medicine, the synthetic biology community is pushing the boundaries by designing microbes that will seek and destroy tumors in the body before self-destructing. Synthetic biology also provides us a way to clean up our environment. We can build organisms to consume toxic chemicals in water or soil that would not otherwise decompose, for example. It can also help us to better understand flu strains and create vaccines. Synthetic biology will even help us feed the world. At MIT, researchers are working to build a process that will allow plants to fix nitrogen. If successful, farmers will no longer require fertilizer for their crops.
That’s not all we’re doing with plants, either. At the Joint BioEnergy Institute in California, scientists have found a way to expand the sugar content of biomass crops to increase their density and decrease the cost of biofuels produced from them. We envision that eventually we will be able to build just about anything from biology. Don’t be surprised if one day your computer has biological parts.
The recently released National Bioeconomy Blueprint notes that the field is already making an important contribution to the U.S.’s technological innovation and will be a key to our shift to a bioeconomy, or economic activity powered by research and innovation in the biosciences.
We still have many challenges to overcome, but we have laid a very strong foundation for the field. We believe that one day we will be able to fully utilize biology’s manufacturing capability. As one of my colleagues, Harvard scientist Pam Silver noted, the field is poised to explode, both in terms of what scientists can accomplish and what the public realizes is possible.
A Significant Advancement
A landmark of synthetic biology will launch this spring. It is an anti-malarial drug made from synthetic chemicals, artemisinin. It’s an important event for those threatened by the disease; each year, malaria kills more than one million people and infects an additional 300–500 million people. That’s over seven percent of the world’s population.
Synthetic biology has learned much from the past.
Artimisinin is not a new treatment for malaria, but our ability to produce the substance in a lab is. Traditionally, the drug is isolated from a plant, Artemisia annua. But by moving production into the lab, we’re liberated from the vicissitudes of the plant’s growth cycle as well as the fluctuations in global supplies and prices. Artemisinin is a milestone in science, too. It represents a watershed moment in particular for the emerging field of synthetic biology.
Managing the Risks
Like many things we do, synthetic biology comes with risks, especially when it comes to safety and security. But consider this: We fly airplanes, we drive cars, we treat cancer with poison— all of these activities could be dangerous, but they also have benefits that far outweigh the risks. We believe this is true of synthetic biology as well. As Laurie Zoloth, a bioethicist at Northwestern University, once said, “Synthetic biology is like iron: You can make sewing needles and you can make spears. Of course, there is going to be dual use.”
Here, I would say that synthetic biology has learned much from the past—at conferences such as Asilomar, we carefully considered how we can pursue our research responsibly. We work closely with regulatory agencies and adhere to our own institutional requirements. In fact, much of our work is with what are called Biosafety Level 1 organisms—the safest organisms known. We also have developed a robust partnership with the FBI to ensure that we are utilizing the best practices for lab security.
In addition to discussing approaches to risk and risk assessment, synthetic biologists are also working hard to minimize potential adverse effects. For example, Silver’s lab is working to create genetic self-destruct traits, termed “auto-delete,” as a way to ensure that genetically modified organisms don’t escape into the environment.
Along with the practical matters of safety and security, there are profound moral and ethical issues involved in our research. Many of us, especially our colleagues at the Hastings Center and the Wilson Center, are grappling with building a framework for all of us to use in our work. There are no easy answers, but I can assure you that we all want our work to benefit the public, solving global challenges, and making sure that we are well-equipped to live in the future bioeconomy...."


http://to.pbs.org/Z0UEAQ

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Dr. James J. Collins, a Pioneer in Synthetic Biology, Joins the Scientific Advisory Board of Agilis Biotherapeutics

Agilis Biotherapeutics, LLC, a synthetic biology-based company focused on developing DNA-based therapeutics for rare genetic diseases, announced today
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Synthetic Biology - Global Strategic Business Report | SYS-CON MEDIA

SYS-CON Media, NJ, The world's leading i-technology media company on breaking technology news.
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