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A Biological 2-Input Decoder Circuit in Human Cells

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Guinn M, Bleris L.

"Decoders are combinational circuits that convert information from n-inputs to a maximum of 2n outputs. This operation is of major importance in computing systems yet it is vastly underexplored in synthetic biology. Here, we present a synthetic gene network architecture that operates as a biological decoder in human cells, converting 2 inputs to 4 outputs. As a proof-of-principle, we use small molecules to emulate the two inputs and fluorescent reporters as the corresponding four outputs. The experiments are performed using transient transfections in human kidney embryonic cells and the characterization by fluorescence microscopy and flow cytometry. We show a clear separation between the ON and OFF mean fluorescent intensity states. Additionally, we adopt the integrated mean fluorescence intensity for the characterization of the circuit and show that this metric is more robust to transfection conditions when compared to the mean fluorescent intensity. To conclude, we present the first implementation of a genetic decoder. This combinatorial system can be valuable towards engineering higher-order circuits as well as accommodate a multiplexed interface with endogenous cellular functions."


http://bit.ly/1q1jqyC

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Synthetic chemistry fuels interdisciplinary approaches to the production of artemisinin

Synthetic chemistry fuels interdisciplinary approaches to the production of artemisinin | SynBioFromLeukipposInstitute | Scoop.it
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Michael A. Corsello and    Neil K. Garg

"In the developing world, multi-drug resistant malaria caused by the parasite Plasmodium falciparum is an epidemic that claims the lives of 1–3 million people per year. Artemisinin, a naturally occurring small molecule that has seen little resistance from malarial parasites, is a valuable weapon in the fight against this disease. Several easily accessible artemisinin derivatives, including artesunate and artemether, display potent antimalarial activity against drug-resistant malaria strains; however, the global supply of artemisinin from natural sources alone remains highly inconsistent and unreliable. As a result, several approaches to artemisinin production have been developed, spanning areas such as total synthesis, flow chemistry, synthetic biology, and semi-synthesis. This review highlights achievements in all areas, in addition to the interplay between synthetic biology and synthetic chemistry that has fueled the recent industrial-scale production of artemisinin."


 http://rsc.li/ZVvuLl

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'Starfish' crystals could lead to 3D-printed pills - Futurity

'Starfish' crystals could lead to 3D-printed pills - Futurity | SynBioFromLeukipposInstitute | Scoop.it
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*‘STARFISH’ CRYSTALS COULD LEAD TO 3D-PRINTED PILLS*

by
Nicole Casal Moore-Michigan 

"Engineers have figured out how to make rounded crystals with no facets, a design that mimics the hard-to-duplicate texture of starfish shells.

The discovery could one day lead to 3D-printed medications that absorb better into the body.
Both the crystals’ shape and the way they’re made—using organic vapor jet printing—have other promising applications, researchers say. The geometry could potentially be useful to guide light in advanced LEDs, solar cells, and nonreflective surfaces...."


 http://bit.ly/1tdFCve

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Next Generation: Freeze-Dried Gene Networks - Scientist

Next Generation: Freeze-Dried Gene Networks - Scientist | SynBioFromLeukipposInstitute | Scoop.it
Researchers devise a way to preserve bits of paper containing synthetic gene networks, which can be easily stored and widely distributed. Rehydrated, transcription and translation “come to life.”
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2.1/Quick summary of history of bioethics. MOOC iGEM HS - YouTube

Where did all the concerns about Synthetic Biology come from? What is bioethics? It is the ethical discussion relevant to biological researches. How can we a...
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BIO·FICTION

BIO·FICTION | SynBioFromLeukipposInstitute | Scoop.it
Bio-Fiction festival announces the shortlisted films on art and synthetic biology, with #VIDAAwards artists – http://t.co/pUpRsb23mQ
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Purified cell-free systems as standard parts for synthetic biology

Purified cell-free systems as standard parts for synthetic biology | SynBioFromLeukipposInstitute | Scoop.it
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by
Hideaki Matsubayashi, Takuya Ueda

"A cell free protein synthesis approach is extensively used for biochemical and synthetic biology researches. Unlike lysate based cell free systems, the PURE system is reconstituted with individually purified factors essential for transcriptional and translational processes. Hence, the components in the PURE system can be definitely manipulated as per the desired situation. Because of this high controllability, the PURE system has been applied to a wide range of research scene, such as biochemical analysis in reconstructed system, in vitro protein engineering, reconstitution of an artificial cell. We believe that this purified cell-free protein synthesis system become a basal technology to advance synthetic biology."

http://bit.ly/1t6YrQz

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Sequence Design for a Test Tube of Interacting Nucleic Acid Strands

Sequence Design for a Test Tube of Interacting Nucleic Acid Strands | SynBioFromLeukipposInstitute | Scoop.it
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by
Wolfe BR, Pierce NA.

"We describe an algorithm for designing the equilibrium base-pairing properties of a test tube of interacting nucleic acid strands. A target test tube is specified as a set of desired “on-target” complexes, each with a target secondary structure and target concentration, and a set of undesired “off-target” complexes, each with vanishing target concentration. Sequence design is performed by optimizing the test tube ensemble defect, corresponding to the concentration of incorrectly paired nucleotides at equilibrium evaluated over the ensemble of the test tube. To reduce the computational cost of accepting or rejecting mutations to a random initial sequence, the structural ensemble of each on-target complex is hierarchically decomposed into a tree of conditional subensembles, yielding a forest of decomposition trees. Candidate sequences are evaluated efficiently at the leaf level of the decomposition forest by estimating the test tube ensemble defect from conditional physical properties calculated over the leaf subensembles. As optimized subsequences are merged toward the root level of the forest, any emergent defects are eliminated via ensemble redecomposition and sequence reoptimization. After successfully merging subsequences to the root level, the exact test tube ensemble defect is calculated for the first time, explicitly checking for the effect of the previously neglected off-target complexes. Any off-target complexes that form at appreciable concentration are hierarchically decomposed, added to the decomposition forest, and actively destabilized during subsequent forest reoptimization. For target test tubes representative of design challenges in the molecular programming and synthetic biology communities, our test tube design algorithm typically succeeds in achieving a normalized test tube ensemble defect ≤1% at a design cost within an order of magnitude of the cost of test tube analysis."

http://bit.ly/ZFjGwL

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BioTechniques - Synthetic Biology: You Can Contribute Too!

BioTechniques - Synthetic Biology: You Can Contribute Too! | SynBioFromLeukipposInstitute | Scoop.it
As the iGEM teams around the world rush to complete their projects for the
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Applications of Membrane Computing in Systems and Synthetic Biology » Free download eBook

Applications of Membrane Computing in Systems and Synthetic Biology » Free download eBook | SynBioFromLeukipposInstitute | Scoop.it
Membrane Computing was introduced as a computational paradigm in Natural Computing. The models introduced, called Membrane (or P) Systems, provide a coherent platform to describe and study l
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BioHacking, Synthetic Biology, and DIYBio - Maker Faire Charlottesville

Jameson Dungan spoke at C'ville Makerfaire about Synthetic Biology and BioLogik Labs. 10.4.14.
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The university experiment

The university experiment | SynBioFromLeukipposInstitute | Scoop.it
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*Nature Special*

 "The accelerating pace of change in today’s world means that universities must modify how they fulfil their function”  http://bit.ly/1ubWmPC

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Ultrasound powers devices deep inside the body

Ultrasound powers devices deep inside the body | SynBioFromLeukipposInstitute | Scoop.it
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 Tom Abate

"Researchers would like to place very small implants deep inside our bodies to monitor health or treat pain. But providing electric power to implants without wires or batteries has been a big obstacle.

Now, engineers are developing a way to send power—safely and wirelessly—to “smart chips” programmed to perform medical tasks and report back the results.
The approach involves beaming ultrasound at a tiny device inside the body designed to do three things: convert the incoming sound waves into electricity, process and execute medical commands, and report the completed activity via a tiny built-in radio antenna.
“We think this will enable researchers to develop a new generation of tiny implants designed for a wide array of medical applications,” says Amin Arbabian, assistant professor of electrical engineering at Stanford University.
Arbabian’s team recently presented a working prototype of this wireless medical implant system at the IEEE Custom Integrated Circuits Conference in San Jose, California.
TINY, WIRELESS NODES
The researchers chose ultrasound to deliver wireless power to their medical implants because it has been safely used in many applications, such as fetal imaging, and can provide sufficient power to implants a millimeter or less in size.
Now, Arbabian and his colleagues are collaborating with other researchers to develop sound-powered implants for a variety of medical applications, including studying the nervous system and treating the symptoms of Parkinson’s disease.
“Tiny, wireless nodes such as these have the potential to become a key tool for addressing neurological disorders,” says Florian Solzbacher, professor of electrical and computer engineering at University of Utah and director of its Center for Engineering Innovation.
POWERED BY PIEZOELECTRICITY

The implant chip is powered by piezoelectricity, which is electricity caused by pressure....." 

http://bit.ly/1vALu3v

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▶ How hackers transform biology into building material

How do you transform mushrooms into furniture, or re-wire algae to conduct electricity? Biohacking, the practice of rewiring the biology of living organisms ...
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Orthogonal optogenetic triple-gene control in mammalian cells

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Konrad Müller , Raphael Engesser , Jens Timmer , Matias D. Zurbriggen , and Wilfried Weber

"Optogenetic gene switches allow gene expression control at an unprecedented spatiotemporal resolution. Recently, light-responsive transgene expression systems that are activated by UV-B, blue or red light have been developed. These systems perform well on their own, but their integration into genetic networks has been hampered by the overlapping absorbance spectra of the photoreceptors. We identified a lack of orthogonality between UV-B and blue light-controlled gene expression as the bottleneck and employed a model-based approach that identified the need for a blue light-responsive gene switch that is insensitive to low-intensity light. Based on this prediction we developed a blue light-responsive and rapidly-reversible expression system. Finally, we employed this expression system to demonstrate orthogonality between UV-B, blue and red/far-red light-responsive gene switches in a single mammalian cell culture. We expect this approach to enable the spatiotemporal control of gene networks and to expand the applications of optogenetics in synthetic biology."



http://bit.ly/1xxyEA9

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Programming Nature - Entrepreneurs are Transforming Synthetic Biology into Real Dollars - YouTube

When: Tuesday, January 22, 2013 Where: Cemex Auditorium at Knight Management Center (Parking and Directions) Event Description: Synthetic biology was once-up...
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iGEM Uppsala 2014 - YouTube

We are the Uppsala iGEM team of 2014. iGEM is a research competition for University students from all over the World, and we are one of Three Swedish Viking ...
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Synthetic biology on ordinary paper, results off the page (w/video)

Synthetic biology on ordinary paper, results off the page (w/video) | SynBioFromLeukipposInstitute | Scoop.it
Nanowerk is the leading nanotechnology portal, committed to educate, inform and inspire about nanotechnologies, nanosciences, and other emerging technologies
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Programming Life: Engineering Student Creativity using Synthetic Biology | BCoE

RT @mnlimas: .@BCoE_LMSA Webinar "Programming Life: Engineering Student Creativity using Synthetic Biology" http://t.co/WBu2PKZDhJ #synbio …
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Frontiers | Enhancing Stress-Resistance for Efficient Microbial Biotransformations by Synthetic Biology | Synthetic Biology

Chemical conversions mediated by microorganisms, otherwise known as microbial biotransformations, are playing an increasingly important role within the biotechnology industry. Unfortunately, the gr...
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Synthetic Biology in Action*: *Developing a drug against multi-drug resistantstrains of Mycobacterium tuberculosis

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by
Saxena A, Mukherjee U, Kumari R, Singh P, Lal R.

"The amalgamation of the research efforts of biologists, chemists and geneticists led by scientists at the Department of Zoology, University of Delhi has resulted in the development of a novel rifamycin derivative; 24-desmethylrifampicin, which is highly effective against multi-drug resistant (MDR) strains of Mycobacterium tuberculosis. The production of rifamycin analogue was facilitated by genetic-synthetic strategies that have opened an interdisciplinary route for the development of more such rifamycin analogues aiming at a better therapeutic potential. The results of this painstaking effort of nearly 25 years of a team of students and scientists led by Professor Rup Lal have been recently published in the Journal of Biological Chemistry (www.jbc.org/content/289/30/21142.long). This strategy can now find applications for developing newer rifamycin analogues that can be harnessed to overcome the problem of MDR, extensively drug resistant (XDR) and totally drug resistant (TDR) M. tuberculosis."

http://1.usa.gov/1puAyNu

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Synthetic Biology Blogs

Synthetic Biology Blogs | SynBioFromLeukipposInstitute | Scoop.it
I thought it might be useful to compile a list of Synthetic Biology blogs that can be used as alternative sources of information and perspectives complementing academic journals.
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Rational Design of a Fusion Protein to Exhibit Disulfide-Mediated Logic Gate Behavior

Rational Design of a Fusion Protein to Exhibit Disulfide-Mediated Logic Gate Behavior | SynBioFromLeukipposInstitute | Scoop.it
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by
Jay H. Choi and Marc Ostermeier 

"Synthetic cellular logic gates are primarily built from gene circuits owing to their inherent modularity. Single proteins can also possess logic gate functions and offer the potential to be simpler, quicker, and less dependent on cellular resources than gene circuits. However, the design of protein logic gates that are modular and integrate with other cellular components is a considerable challenge. As a step toward addressing this challenge, we describe the design, construction, and characterization of AND, ORN, and YES logic gates built by introducing disulfide bonds into RG13, a fusion of maltose binding protein and TEM-1 β-lactamase for which maltose is an allosteric activator of enzyme activity. We rationally designed these disulfide bonds to manipulate RG13’s allosteric regulation mechanism such that the gating had maltose and reducing agents as input signals, and the gates could be toggled between different gating functions using redox agents, although some gates performed sub optimally."

http://bit.ly/1FdmUIV

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CRISPR-mediated direct mutation of cancer genes in the mouse liver

CRISPR-mediated direct mutation of cancer genes in the mouse liver | SynBioFromLeukipposInstitute | Scoop.it
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Wen Xue, Sidi Chen, Hao Yin, Tuomas Tammela, Thales Papagiannakopoulos, Nikhil S. Joshi, Wenxin Cai, Gillian Yang, Roderick Bronson, Denise G. Crowley, Feng Zhang, Daniel G. Anderson, Phillip A. Sharp & Tyler Jacks

"The study of cancer genes in mouse models has traditionally relied on genetically-engineered strains made via transgenesis or gene targeting in embryonic stem cells1. Here we describe a new method of cancer model generation using the CRISPR/Cas (clustered regularly interspaced short palindromic repeats/CRISPR-associated proteins) system in vivo in wild-type mice. We used hydrodynamic injection to deliver a CRISPR plasmid DNA expressing Cas9 and single guide RNAs (sgRNAs)2, 3, 4 to the liver that directly target the tumour suppressor genes Pten (ref. 5) and p53 (also known as TP53 and Trp53) (ref. 6), alone and in combination. CRISPR-mediated Pten mutation led to elevated Akt phosphorylation and lipid accumulation in hepatocytes, phenocopying the effects of deletion of the gene using Cre–LoxP technology7, 8. Simultaneous targeting of Pten and p53 induced liver tumours that mimicked those caused by Cre–loxP-mediated deletion of Pten and p53. DNA sequencing of liver and tumour tissue revealed insertion or deletion mutations of the tumour suppressor genes, including bi-allelic mutations of both Pten and p53 in tumours. Furthermore, co-injection of Cas9 plasmids harbouring sgRNAs targeting the β-catenin gene and a single-stranded DNA oligonucleotide donor carrying activating point mutations led to the generation of hepatocytes with nuclear localization of β-catenin. This study demonstrates the feasibility of direct mutation of tumour suppressor genes and oncogenes in the liver using the CRISPR/Cas system, which presents a new avenue for rapid development of liver cancer models and functional genomics."

http://bit.ly/1wdKW20

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Stimuli-sensitive intrinsically disordered protein brushes

Stimuli-sensitive intrinsically disordered protein brushes | SynBioFromLeukipposInstitute | Scoop.it
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by
Nithya Srinivasan, Maniraj Bhagawati, Badriprasad Ananthanarayanan & Sanjay Kumar

"Grafting polymers onto surfaces at high density to yield polymer brush coatings is a widely employed strategy to reduce biofouling and interfacial friction. These brushes almost universally feature synthetic polymers, which are often heterogeneous and do not readily allow incorporation of chemical functionalities at precise sites along the constituent chains. To complement these synthetic systems, we introduce a biomimetic, recombinant intrinsically disordered protein that can assemble into an environment-sensitive brush. This macromolecule adopts an extended conformation and can be grafted to solid supports to form oriented protein brushes that swell and collapse dramatically with changes in solution pH and ionic strength. We illustrate the value of sequence specificity by using proteases with mutually orthogonal recognition sites to modulate brush height in situ to predictable values. This study demonstrates that stimuli-responsive brushes can be fabricated from proteins and introduces them as a new class of smart biomaterial building blocks."

http://bit.ly/1xW8iso

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