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Realizing the promise of biotechnology: Infrastructural-icons in synthetic biology

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Realizing the promise of biotechnology: Infrastructural-icons in synthetic biology

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Adrian MackenzieThat part of synthetic biology concerned with engineering promises to make good on the potential of biotechnology to address problems of food, energy, health and environment. How do the synthetic biologistsrealize the promise of biology as technology? In analysing realization of promise in synthetic biology, I suggest that we should pay close attention to different rates of realization. Synthetic biologists have consistently focused on making particular kinds of devices such as oscillators, timers and clock that both address problems of control over rates, and that themselves resemble and link to other rate-controlling mechanisms such as the many clocks found in large technical systems. They have also, again in those parts of the field concerned with engineering, expended much effort in developing infrastructures, techniques, methods and systems for rapid assembly of parts and components. The clocks and assembly methods function as both as iconic signs and as infrastructural elements or practices that will realise the promise of biotechnology. The field has not only produced what we might call infrastructural-icons for biology as technology, but almost defined itself in terms of a promise of realisation. In analysing how synthetic biology or any other technological endeavour shows how things could be (icons), and makes operational connections between things (infrastructures), the main goal is not to situate field in social or economic contexts. Rather, it is to open a way to see how synthetic biologists and others -- philosophers, social scientists, historians, artists, designers, scientists engineers, as students or consumers–manage to address the gaps that open up as the promise of biology as technology is realized at different rates.
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Understanding and Exploiting Feedback in Synthetic Biology

Understanding and Exploiting Feedback in Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
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*Understanding and Exploiting Feedback in Synthetic Biology* 

by
Taliman Afroz, Chase L. Beisel

"Synthetic biology employs traditional engineering concepts in the construction of cells and organisms. One of the most fundamental concepts is feedback, where the activity of a system is influenced by its output. Feedback can imbue the system with a range of desirable properties such as reducing the rise time or exhibiting an ultrasensitive response. Feedback is also commonly found in nature, further supporting the incorporation of feedback into synthetic biological systems. In this review, we discuss the common attributes of negative and positive feedback loops in gene regulatory networks, whether alone or in combination, and describe recent applications of feedback in metabolic engineering, population control, and the development of advanced biosensors. The examples principally come from synthetic systems in the bacterium Escherichia coli and in the budding yeast Saccharomyces cerevisiae, the two major workhorses of synthetic biology. Through this review, we argue that biological feedback represents a powerful yet underutilized tool that can advance the construction of biological systems."
http://bit.ly/YyiFP5

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For Autodesk, a Step Into a Nanoscale World

For Autodesk, a Step Into a Nanoscale World | SynBioFromLeukipposInstitute | Scoop.it
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By JOHN MARKOFF

"Autodesk, a quirky software start-up in Marin County, north of San Francisco, rose to prominence in the early 1980s because of AutoCAD, its computer-aided design program that was intended for use on personal computers. Over the next decade, AutoCAD became the standard design tool for architects and engineers.

 This week at the TED conference in Long Beach, Calif., the company will take the first public step toward translating its computer design approach, which has since spilled over from Hollywood to the Maker movement, into the emerging nanoscale world of synthetic biology and materials. For the last two years, a small group of software engineers and molecular biologists have been developing a software system for designing at the molecular level at the company’s research laboratory in downtown San Francisco. At the TED conference, Autodesk will introduce “Project Cyborg,” a Web-based software platform for delivering a range of services like molecular modeling and simulation. The company has quietly begun working with a small group of molecular biologists in the last year. It has not announced when it will commercialize the technology, but it envisions that scientists, engineers and even students and “citizen scientists” will soon be able to use the system on individual projects. There are still many open questions that nanotechnology needs to surmount, ranging from viability to safety. Autodesk executives and the designers of Project Cyborg believe, however, that they can recreate the thriving commercial ecosystems that the company has now evolved in engineering design at a Lilliputian scale. They foresee nanorobots that will be able to attack cancers and other diseases and a new world of molecular materials, as well as a visualization system for an entire universe beyond the range of the unaided human eye. “People are only now being introduced to the fact that this form of science is in fact design, and it has the same paradigms and patterns as designing a factory or designing a car, with different nouns and verbs,” said Jeff Kowalski, Autodesk’s chief technology officer. “That’s our objective – to understand how to take 30 years of technology to transform how design is done in the inert world and empower those who are designing in the living world.” The company will introduce its new nanodesign software vision in two talks to be given by scientists who have been working with the Autodesk research lab. One will be delivered by Skylar Tibbits, an M.I.T. architect and computer scientist who is to discuss biomolecular self-assembly on Tuesday. Jessica Green, a University of Oregon ecologist, is to speak on Thursday about design at the molecular scale. Autodesk took its first commercial step into biological design last year with a partnership with Organovo Holdings, a San Diego start-up that aims to manufacture human tissues and organs. Autodesk software will be used to control a so-called bioprinter being developed by Organovo. It will initially have pharmaceutical testing applications. Autodesk is not alone in seeking to build nanoscale design tools, nor the first to try to commercialize molecular design.Thomas Knight, an M.I.T electrical engineer, introduced the concept of biobricks in 2003. The idea has been to create a library of standard biological parts derived from specific DNA sequences. Ideally they would share a common “interface,” making it possible to use them to construct new biological systems. A striking example of the potential of molecular design was announced in February 2012 by the Wyss Institute for Biologically Inspired Engineering at Harvard. Two scientists at the institute designed a robotic device from DNA that was intended to seek out specific cells and deliver anticancer therapeutics with remarkable precision. The nanoscale robot is shaped like a clamshell and designed to open when it reaches its target, releasing a specific molecule. The Autodesk researchers acknowledge they are far from being able to sell commercially robust engineering tools for the nano world. “Right now we don’t even have the notion of digital prototyping in any mature way in biology,” said Carlos Olguin, head of the Autodesk Bio/Nano/Programmable Matter Group. “People really do all of this by trial and error.” But the company is placing a significant bet that that will not always be the case. If Autodesk is right, it will be a tremendous vindication for K. Eric Drexler, an M.I.T.-trained engineer who in the 1970s began forecasting the emergence of a world engineered by nanoscale machines...." 


http://nyti.ms/15eRpuS

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Can You Feel Me Now? The Sensational Rise of Haptic Interfaces

Can You Feel Me Now? The Sensational Rise of Haptic Interfaces | SynBioFromLeukipposInstitute | Scoop.it
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*Can You Feel Me Now*? *The Sensational Rise of Haptic Interfaces*

by
BY NATHAN HURST

"Your first experience with haptics was probably your phone vibrating in your pocket. Or maybe it was the rumble pack on your N64 controller. But whatever the case, you probably didn’t know it as a haptic interface.

Haptics is to touch the way optics is to sight. It's a user interface that circumvents the cluttered inputs of sight and sound, and it's appearing in an increasing number of objects we interact with daily. Vibration is just the beginning.

......

Unlike the feedback-based, interactive vibrations from Surround Haptics, Cadillac, and RISR, the vibrating insoles Jim Collins is working on don't impart information to the user — at least not consciously. Collins — a bioengineer at Boston University and the Wyss Institute at Harvard — found that random vibrations introduced in the feet of participants helped them sway less, or keep their balance better. "It's not a feedback-based system," says Collins, who has been studying the effect for almost 20 years. "What we're doing is introducing a bias signal, to their sensory neurons, which is basically serving as a pedestal or booster for the signals they normally would detect." That is, small vibrations in the feet cause heightened nerve sensitivity, and thus users — including stroke victims, diabetics, the elderly, but also the young and fit — detect signals they would normally miss. The insoles aren't on the market yet, but Collins envisions additional future applications in sports equipment, like ski boots and golf shoes...."


http://bit.ly/YpWVH7

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Reprogramming human fibroblasts to pluripotency using modified mRNA

Reprogramming human fibroblasts to pluripotency using modified mRNA | SynBioFromLeukipposInstitute | Scoop.it
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by
Pankaj K Mandal& Derrick J Rossi

"Induced pluripotent stem (iPS) cells hold the potential to revolutionize regenerative medicine through their capacity to generate cells of diverse lineages for future patient-specific cell-based therapies. To facilitate the transition of iPS cells to clinical practice, a variety of technologies have been developed for transgene-free pluripotency reprogramming. We recently reported efficient iPS cell generation from human fibroblasts using synthetic modified mRNAs. Here we describe a stepwise protocol for the generation of modified mRNA-derived iPS cells from primary human fibroblasts, focusing on the critical parameters including medium choice, quality control, and optimization steps needed for synthesizing modified mRNAs encoding reprogramming factors and introducing these into cells over the course of 2-3 weeks to ensure successful reprogramming. The protocol described herein is for reprogramming of human fibroblasts to pluripotency; however, the properties of modified mRNA make it a powerful platform for protein expression, which has broad applicability in directed differentiation, cell fate specification and therapeutic applications."
http://bit.ly/Wb3d0X

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Biotechdaily - Automated Liquid Handling Platforms Boost Productivity of Synthetic Biology Researchers

Biotechdaily - Automated Liquid Handling Platforms Boost Productivity of Synthetic Biology Researchers | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

By BiotechDaily International staff writers

"Use of automated robotic liquid handling workstations is giving a dramatic push to development efforts in the exciting new field of synthetic biology.

 Synthetic biology is the design and construction of new biological entities such as enzymes, genetic circuits, and cells, or the redesign of existing biological systems. Synthetic biology builds on the advances in molecular, cell, and systems biology and seeks to transform biology in the same way that synthesis transformed chemistry and integrated circuit design transformed computing. "



http://bit.ly/VUWKaA

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Gene synthesis by assembly of deoxyuridine-containing oligonucleotides

Gene synthesis by assembly of deoxyuridine-containing oligonucleotides | SynBioFromLeukipposInstitute | Scoop.it
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by
Romualdas Vaisvila , Jurate Bitinaite

"Gene synthesis is an invaluable technique in synthetic and molecular biology for synthesis of artificial genes, operons, and even genomes. In many cases the traditional methods for obtaining functional DNA sequences through cloning are not applicable due to the novelty of genetic material. Here, we describe the simple and economical DNA synthesis method based on USER™ technology. The method consists of (1) synthesis of building blocks up to 500 bp; (2) assembly of genes up to 3 kb; (3) error correction reassembly; and (4) assembly of operons up to 15 kb if needed."

http://bit.ly/12TGOqX

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RLE Analog Circuits and Biological Systems Group

RLE Analog Circuits and Biological Systems Group | SynBioFromLeukipposInstitute | Scoop.it
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Professor Rahul Sarpeshkar

"We create (1) novel DNA and protein circuits for systems and synthetic biology; (2) implantable medical devices such as cochlear implants and brain-machine interfaces; (3) ultra-energy-efficient, ultra-low-power, and energy-harvesting systems; and, (4) biological and bio-inspired supercomputers. The common theme in all of our work is analog circuit design."
 http://bit.ly/WX5Rps
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Stanford scientists fit light-emitting bioprobe in a single cell

Stanford scientists fit light-emitting bioprobe in a single cell | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

BY ANDREW MYERS

"Stanford researchers are the first to demonstrate that sophisticated light resonators can be inserted inside living cells without damage to the cell. The development marks a new age in which tiny lasers and light-emitting diodes yield new avenues in the study of living cells.If engineers at Stanford have their way, biological research may soon be transformed by a new class of light-emitting probes small enough to be injected into individual cells without harm to the host.

 Welcome to biophotonics, a discipline at the confluence of engineering, biology and medicine in which light-based devices – lasers and light-emitting diodes (LEDs) – are opening up new avenues in the study and influence of living cells. The team described their probe in a paper published online Feb. 13 by the journal Nano Letters. It is the first study to demonstrate that tiny, sophisticated devices known as light resonators can be inserted inside cells without damaging the cell. Even with a resonator embedded inside, a cell is able to function, migrate and reproduce as normal."



http://stanford.io/13gA8P8

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Synthetic biology: Small RNAs improve metabolic engineering

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by

Louisa Flintoft This author show "how synthetic small RNAs (sRNAs) can be used to improve bacterial metabolic engineering. First, they developed an efficient approach to identifying target genes for which downregulation increases the production of a desired compound"


http://bit.ly/WUomLe

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Synthetic Biology: Advancing the Design of Diverse Genetic Systems

Synthetic Biology: Advancing the Design of Diverse Genetic Systems | SynBioFromLeukipposInstitute | Scoop.it
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by
Yen-Hsiang Wang, Kathy Y. Wei, Christina D. Smolke

"A major objective of synthetic biology is to make the process of designing genetically encoded biological systems more systematic, predictable, robust, scalable, and efficient. Examples of genetic systems in the field vary widely in terms of operating hosts, compositional approaches, and network complexity, ranging from simple genetic switches to search-and-destroy systems. While significant advances in DNA synthesis capabilities support the construction of pathway- and genome-scale programs, several design challenges currently restrict the scale of systems that can be reasonably designed and implemented. Thus, while synthetic biology offers much promise in developing systems to address challenges faced in the fields of manufacturing, environment and sustainability, and health and medicine, the realization of this potential is currently limited by the diversity of available parts and effective design frameworks. As researchers make progress in bridging this design gap, advances in the field hint at ever more diverse applications for biological systems."

http://bit.ly/WLS7fN

Illustration http://en.wikipedia.org/wiki/Biological_systems

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Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols

Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:


*Engineering cells for more efficient biofuel production*

by
Anne Trafton

"In the search for renewable alternatives to gasoline, heavy alcohols such as isobutanol are promising candidates. Not only do they contain more energy than ethanol, but they are also more compatible with existing gasoline-based infrastructure. For isobutanol to become practical, however, scientists need a way to reliably produce huge quantities of it from renewable sources. 

 MIT chemical engineers and biologists have now devised a way to dramatically boost isobutanol production in yeast, which naturally make it in small amounts. They engineered yeast so that isobutanol synthesis takes place entirely within mitochondria, cell structures that generate energy and also host many biosynthetic pathways. Using this approach, they were able to boost isobutanol production by about 260 percent. 

Though still short of the scale needed for industrial production, the advance suggests that this is a promising approach to engineering not only isobutanol but other useful chemicals as well, says Gregory Stephanopoulos, an MIT professor of chemical engineering and one of the senior authors of a paper describing the work in the Feb. 17 online edition of Nature Biotechnology...." 

http://bit.ly/Xmy8Ct

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*Compartmentalization of metabolic pathways in yeast mitochondria improves the production of branched-chain alcohols*

by
José L Avalos,Gerald R Fink& Gregory Stephanopoulos

"Efforts to improve the production of a compound of interest in Saccharomyces cerevisiae have mainly involved engineering or overexpression of cytoplasmic enzymes. We show that targeting metabolic pathways to mitochondria can increase production compared with overexpression of the enzymes involved in the same pathways in the cytoplasm. Compartmentalization of the Ehrlich pathway into mitochondria increased isobutanol production by 260%, whereas overexpression of the same pathway in the cytoplasm only improved yields by 10%, compared with a strain overproducing enzymes involved in only the first three steps of the biosynthetic pathway. Subcellular fractionation of engineered strains revealed that targeting the enzymes of the Ehrlich pathway to the mitochondria achieves greater local enzyme concentrations. Other benefits of compartmentalization may include increased availability of intermediates, removing the need to transport intermediates out of the mitochondrion and reducing the loss of intermediates to competing pathways."

http://bit.ly/12HvL4b

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Electrochemical Analysis of Shewanella oneidensis Engineered To Bind Gold Electrodes

Electrochemical Analysis of Shewanella oneidensis Engineered To Bind Gold Electrodes | SynBioFromLeukipposInstitute | Scoop.it
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by
Aunica L. Kane, Daniel R. Bond, and Jeffrey A. Gralnick

"Growth in three-electrode electrochemical cells allows quantitative analysis of mechanisms involved in electron flow from dissimilatory metal reducing bacteria to insoluble electron acceptors. In these systems, gold electrodes are a desirable surface to study the electrophysiology of extracellular respiration, yet previous research has shown that certain Shewanella species are unable to form productive biofilms on gold electrodes. To engineer attachment of Shewanella oneidensis to gold, five repeating units of a synthetic gold-binding peptide (5rGBP) were integrated within an Escherichia coli outer membrane protein, LamB, and displayed on the outer surface of S. oneidensis. Expression of LamB-5rGBP increased cellular attachment of S. oneidensis to unpoised gold surfaces but was also associated with the loss of certain outer membrane proteins required for extracellular respiration. Loss of these outer membrane proteins during expression of LamB-5rGBP decreased the rate at which S. oneidensis was able to reduce insoluble iron, riboflavin, and electrodes. Moreover, poising the gold electrode resulted in repulsion of the engineered cells. This study provides a strategy to specifically immobilize bacteria to electrodes while also outlining challenges involved in merging synthetic biology approaches with native cellular pathways and cell surface charge."


http://bit.ly/Y3UvOe

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Modeling the effect of cell division on genetic oscillators

Modeling the effect of cell division on genetic oscillators | SynBioFromLeukipposInstitute | Scoop.it
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*Modeling the effect of cell division on genetic oscillators*

by
Gonze D.

"Many genetic oscillators (circadian clocks, synthetic oscillators) continue to oscillate accross the cell division cycle. Since cell divisions create discontinuities in the dynamics of genetic oscillators the question about the resilience of oscillations and the factors that contribute to the robustness of the oscillations may be raised. We study here, through stochastic simulations, the effect of the cell division cycle on genetic oscillations using the Repressilator - a genetic oscillator developed in the context of synthetic biology. We consider intrinsic noise (molecular noise due to the limited number of molecules) and extrinsic noise (variability in the cell division time and in the partition of the molecules into daughter cells, cell-cell variability in kinetic parameters, etc). Our numerical simulations show that, although noisy, oscillations are quite resilient to cell division and that cell-cell heterogeneity may be the main source of variability observed experimentally. Finally, similar simulations performed with another model, the Goodwin model, show that oscillations may be entrained and synchronized by cell division. This highlights the influence of the clock architecture on the robustness of genetic oscillations. Our approach provides a general framework to study the effect of cell division on dynamical systems and several possible extensions are described."

http://bit.ly/ZGXAsy

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Reading and writing omes

Reading and writing omes | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

*Reading and writing ones* 

by
Church GM.

"‘Systems Technologies' are increasingly potent drivers of biological research. Molecular Systems Biology will be illustrating this evolution with a new Reviews Series highlighting key technologies in systems medicine, genome-scale, computational, quantitative and synthetic biology. The series is launched with a review from the Snyder group on reading human omes (Soon et al, 2013) and a companion review on writing genomes from Harvard's Wyss Institute (Esvelt and Wang, 2013)."

http://1.usa.gov/15eSz9H

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4th International Conference on Biomolecular Engineering Tackles New Challenges with Synthetic Biology

4th International Conference on Biomolecular Engineering Tackles New Challenges with Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
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Keynote Presentation: George Church: Microbial and Human Multiplex Genome 
Synthetic Biology: Chris Voighttp://bit.ly/11SUaV0 see alsohttp://bit.ly/XBLVoN
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Lipid Nanotechnology

Lipid Nanotechnology | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

*Lipid Nanotechnology*

by
Mashaghi S, Jadidi T, Koenderink G, Mashaghi A.

"Nanotechnology is a multidisciplinary field that covers a vast and diverse array of devices and machines derived from engineering, physics, materials science, chemistry and biology. These devices have found applications in biomedical sciences, such as targeted drug delivery, bio-imaging, sensing and diagnosis of pathologies at early stages. In these applications, nano-devices typically interface with the plasma membrane of cells. On the other hand, naturally occurring nanostructures in biology have been a source of inspiration for new nanotechnological designs and hybrid nanostructures made of biological and non-biological, organic and inorganic building blocks. Lipids, with their amphiphilicity, diversity of head and tail chemistry, and antifouling properties that block nonspecific binding to lipid-coated surfaces, provide a powerful toolbox for nanotechnology. This review discusses the progress in the emerging field of lipid nanotechnology.

..."

http://bit.ly/XTppH7
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Interview: Jason Silva - Synthetic Biology

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Interview: 
*Jason Silva* - *Synthetic Biology* 


http://bit.ly/13AxP9Y

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IWBDA: International Workshop on Biodesign Automation

IWBDA: International Workshop on Biodesign Automation | SynBioFromLeukipposInstitute | Scoop.it
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via +Michal Galdzicki 

*5th International Workshop on Bio-Design Automation*

"About IWBDA The Fifth International Workshop on Bio-Design Automation (IWBDA) co-located with SB6.0 will bring together researchers from the synthetic biology, systems biology, and design automation communities. The focus is on concepts, methodologies and software tools for the computational analysis of biological systems and the synthesis of biological systems. Still in its early stages, the field of synthetic biology has been driven by experimental expertise; much of its success can be attributed to the skill of the researchers in specific domains of biology. There has been a concerted effort to assemble repositories of standardized components. However, creating and integrating synthetic components remains an ad hoc process. The field has now reached a stage where it calls for computer-aided design tools. The electronic design automation (EDA) community has unique expertise to contribute to this endeavor. This workshop offers a forum for cross-disciplinary discussion, with the aim of seeding collaboration between the research communities. Topics of interest include: Design methodologies for synthetic biology.Standardization of biological components.Automated assembly techniques.Computer-aided modeling and abstraction techniques.Engineering methods inspired by biology.Domain specific languages for synthetic biology.Data exchange standards and models for synthetic biology.Call for Abstracts Abstracts should be two pages long, following the ACM SIG Proceedings templates at http://www.acm.org/sigs/publications/proceedings-templates. Indicate whether you would like your abstract considered for a poster presentation, an oral presentation, or both. Include the full names, affiliations and contact information of all authors. Abstracts will be reviewed by the Program Committee. Those that are selected for oral and poster presentations will distributed to workshop participants and posted on the workshop website. The submission system will be opened shortly. Key Dates Call for participation published: TBDAbstract submission deadline: TBDAbstract acceptance notification: TBDWorkshop: July 12-13, 2013Dates and Venue The workshop will take place following BioBricks Foundation SB6.0: The Sixth International Meeting on Synthetic Biology at Imperial College, London, UK. Lodging during the conference will be available at Imperial College and at hotels close by. Agenda The conference program is current in development Organizing Committee Executive Committee General Chair - Jonathan Babb (jbabb@mit.edu)Finance Co-Chair - Aaron Adler (aadler at bbn dot com)Finance Co-Chair - Traci Haddock (tracihaddock@gmail.com)Program Committee Co-Chair - Leonidas Bleris (bleris@utdallas.edu)Program Committee Co-Chair - Ilias Tagkopoulos (iliast@cs.ucdavis.edu)Industry Liaison Chair - Jose Pacheco (jose@igem.org)Publication Chair - Michal Galdzicki (mgaldzic@uw.edu)Steering Committee Douglas Densmore (ougd@bu.edu)Soha Hassoun (soha@cs.tufts.edu)Natasa Miskov-Zivanov (nam66@pitt.edu)Marc Riedel (mriedel@umn.edu)Ron Weiss (rweiss@mit.edu)"
http://bit.ly/13p2WFj ;
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3-D Printed Body Parts, Finally!s

3-D Printed Body Parts, Finally!s | SynBioFromLeukipposInstitute | Scoop.it
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by
NIC HALVERSON

"For children born with microtia, a congenital deformity of the external ear, reconstructive surgery solutions can involve long, painful operations or prosthetics that rarely resemble the real thing.

 However, Cornell bioengineers and physicians have offered new hope by using 3-D printing and injectable gel molds to create an artificial ear that looks, feels and functions like a natural one. Dr. Jason Spector, director of the Laboratory for Bioregenerative Medicine and Surgery and associate professor of plastic surgery at Weill Cornell Medical College, said this method is "absolutely" the best option reconstructive surgeons have for helping kids with microtia or those who've lost part of an ear to trauma or cancer...."



 http://bit.ly/12TxoMc

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DNA Transistor

DNA Transistor | SynBioFromLeukipposInstitute | Scoop.it
REPLACE
Gerd Moe-Behrens's insight:

by
Binquan Luan

IBM computational biology center  

"Nanotechnology for DNA Sequencing

The information to produce many of the components of the cell such as RNAs and proteins is encoded in the sequence of nucleotides of a cell. Determining the DNA sequence is therefore fundamental to molecular biology and medicine. The most used technique for DNA sequencing has been the dideoxy termination method developed by F. Sanger in a Nobel Prize winning groundbreaking work. Through parallelization, automation and refinement of the established Sanger sequencing method, the Human Genome Project is estimated to have cost $3 billion. Much lower cost methods for DNA sequencing will be required to make genome sequencing feasible for routine healthcare practice.Many new generation sequencing methods have been developed during the last decade, which represent significant advances over the traditional Sanger sequencing. Amongst them, a method based on threading a DNA molecule through a pore of a diameter of a few nanometers to sequence this molecule while it translocates through the nanopore occupies a privileged place. DNA nanopore sequencing has the advantage of being a real-time single molecule DNA sequencing method with little to no sample preparation and inherently of low-cost.At least two technical roadblocks prevent implementations of DNA nanopore nucleotide identification by electrical sensor methods. 1) The absence of a reliable approach to control the translocation of DNA through the nanopore. 2) The technical difficulties in making sufficiently small sensors. Our work in this field focuses on solving the challenge of translocation control.To control the DNA translocation through the nanopore we have proposed a device consisting of a metal/dielectric/metal/dielectric/metal multilayer nano-structure built into the membrane that contains the nanopore. Voltage biases between the electrically addressable metal layers will modulate the electric field inside the nanopore. This device utilizes the interaction of discrete charges along the backbone of a DNA molecule with the modulated electric field to trap DNA in the nanopore with single-base resolution. By cyclically turning on and off these gate voltages, we showed theoretically, and we expect to be able prove experimentally, the plausibility to move DNA through the nanopore at a rate of one nucleotide per cycle. We call this device a DNA transistor, as a DNA current is produced in response to modulation of gate voltages in the device.The DNA transistor is then a DNA positional controlling platform with single-base-resolution, which could be used in combination with sensor measurements that are under development by us and other research groups. By providing enough dwell time for each DNA nucleotide at the electrodes constituting the sensor, the DNA transistor allows exploration of the best electrical sensor that can resolve the difference between the four DNA nucleotides. In that sense, the DNA transistor paves the way to nanopore-based nucleotide sequencing, and personalized "



http://bit.ly/TJ6h3c

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Workshop on Semiconductor Concepts from Synthetic Biology (SemiSynBio)

Workshop on Semiconductor Concepts from Synthetic Biology (SemiSynBio) | SynBioFromLeukipposInstitute | Scoop.it
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Date: Friday, Feb. 22, 2013, 8 a.m. — Saturday, Feb. 23, noon Local
Location: The Charles Hotel, Harvard Square, One Bennett Street, Longfellow Room, Cambridge, MA, United States

EXPECTED OUTCOME

The goal of the SemiSynBio workshop is to identify future research directions for the semiconductor industry based on concepts and principles derived from Synthetic Biology (e.g. highly functional space-limited digital and analog systems that operate with extremely low energy consumption etc.).

http://bit.ly/YGv3wR

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Research Biobanks Meet Synthetic Biology: Autonomy and Ownership

Research Biobanks Meet Synthetic Biology: Autonomy and Ownership | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Stephen R. Munzer

"Two examples of research biobanks are discussed. The first is a set of stored blood samples taken from Havasupai Indians by scientists at Arizona State University (ASU). The second is a set of zinc finger proteins (ZFPs) and zinc finger nucleases (ZFNs) assembled by Sangamo BioSciences, Inc. of California. Both examples involve individual and group autonomy, informational asymmetries, and exchange. Both examples are controversial but for different reasons. In the Havasupai case, the Indians claimed that the scientists used the blood samples to analyze a Havasupai predisposition to diabetes, to which they consented, and to extract information about Havasupai inbreeding, schizophrenia, and geographical origins, to which the Indians did not consent. Eventually, ASU returned the blood samples and compensated the tribe and some individual members. Scrutiny shows that the Havasupai complaints were mainly justified. As to ZFPs and ZFNs, some lawyer-scientists contend that Sangamo’s preeminent patent and trade secret position unfairly hinders others from benefiting from Sangamo’s knowledge. Close examination shows no unfairness in the Sangamo case, for two reasons. First, the Zinc Finger Consortium provided an open access alternative to dealing with Sangamo. Second, under standard economic criteria Sangamo did not have a monopoly on zinc finger technology."
http://bit.ly/11STA9M

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http://en.wikipedia.org/wiki/Havasupai_people

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Customized optimization of metabolic pathways by combinatorial transcriptional engineering

Customized optimization of metabolic pathways by combinatorial transcriptional engineering | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

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Jing Du, Yongbo Yuan, Tong Si, Jiazhang Lian and Huimin Zhao

"A major challenge in metabolic engineering and synthetic biology is to balance the flux of an engineered heterologous metabolic pathway to achieve high yield and productivity in a target organism. Here, we report a simple, efficient and programmable approach named ‘customized optimization of metabolic pathways by combinatorial transcriptional engineering (COMPACTER)’ for rapid tuning of gene expression in a heterologous pathway under distinct metabolic backgrounds. Specifically, a library of mutant pathways is created by de novo assembly of promoter mutants of varying strengths for each pathway gene in a target organism followed by high-throughput screening/selection. To demonstrate this approach, a single round of COMPACTER was used to generate both a xylose utilizing pathway with near-highest efficiency and a cellobiose utilizing pathway with highest efficiency that were ever reported in literature for both laboratory and industrial yeast strains. Interestingly, these engineered xylose and cellobiose utilizing pathways were all host-specific. Therefore, COMPACTER represents a powerful approach to tailor-make metabolic pathways for different strain backgrounds, which is difficult if not impossible to achieve by existing pathway engineering methods."

http://bit.ly/WUhygz

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Sequence Controlled Self-Knotting Colloidal Patchy Polymers

Sequence Controlled Self-Knotting Colloidal Patchy Polymers | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:


*Bionic Proteins*: *Nano-Machines Recreate Protein Activities*

by
editorial staff, ScienceDaily 

"Physicists of the University of Vienna together with researchers from the University of Natural Resources and Life Sciences Vienna developed nano-machines which recreate principal activities of proteins. They present the first versatile and modular example of a fully artificial protein-mimetic model system, thanks to the Vienna Scientific Cluster (VSC), a high performance computing infrastructure. These "bionic proteins" could play an important role in innovating pharmaceutical research."
http://bit.ly/WSHKZ5

comment to this original research paper:

*Sequence Controlled Self-Knotting Colloidal Patchy Polymers*

by

 Ivan Coluzza, Peter D. J. van Oostrum, Barbara Capone, Erik Reimhult, and Christoph Dellago

"Knotted chains are a promising class of polymers with many applications for materials science and drug delivery. Here we introduce an experimentally realizable model for the design of chains with controllable topological properties. Recently, we have developed a systematic methodology to construct self-assembling chains of simple particles, with final structures fully controlled by the sequence of particles along the chain. The individual particles forming the chain are colloids decorated with mutually interacting patches, which can be manufactured in the laboratory with current technology. Our methodology is applied to the design of sequences folding into self-knotting chains, in which the end monomers are by construction always close together in space. The knotted structure can then be externally locked simply by controlling the interaction between the end monomers, paving the way to applications in the design and synthesis of active materials and novel carriers for drugs delivery."

http://bit.ly/12ZMEXA

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