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Outlines on nanotechnologies applied to bladder tissue engineering

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Alberti C.

"Tissue engineering technologies are more and more expanding as consequence of recent developments in the field of biomaterial science and nanotechnology research. An important issue in designing scaffold materials is that of recreating the ECM (extra-cellular matrix) functional features - particularly ECM-derived complex molecule signalling - to mimic its capability of directing cell-growth and neotissue morphogenesis. In this way the nanotechnology may offer intriguing chances, biomaterial nanoscale-based scaffold geometry behaving as nanomechanotransducer complex interacting with different cell nanosize proteins, especially with those of cell surface mechanoreceptors. To fabricate 3D-scaffold complex architectures, endowed with controlled geometry and functional properties, bottom-up approaches, based on molecular self-assembling of small building polymer units, are used, sometimes functionalizing them by incorporation of bioactive peptide sequences such as RDG (arginine - glycine - aspartic acid, a cell-integrin binding domain of fibronectin), whereas the top-down approaches are useful to fabricate micro/nanoscale structures, such as a microvasculature within an existing complex bioarchitecture. Synthetic polymer-based nanofibers, produced by electrospinning process, may be used to create fibrous scaffolds that can facilitate, given their nanostructured geometry and surface roughness, cell adhesion and growth. Also bladder tissue engineering may benefit by nanotechnology advances to achieve a better reliability of the bladder engineered tissue. Particularly, bladder smooth muscle cell adhesion to nanostructured polymeric surfaces is significantly enhanced in comparison with that to conventional biomaterials. Moreover nanostructured surfaces of bladder engineered tissue show a decreased calcium stone production. In a bladder tumor animal model, the dispersion of carbon nanofibers in a polymeric scaffold-based tissue engineered replacement neobladder, appears to inhibit a carcinogenic relapse in bladder prosthetic material. Facing the future, a full success of bladder tissue engineering will mainly depend on the progress of both biomaterial nanotechnologies and stem cell biology research..."
http://1.usa.gov/QLINT9

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Deciphering the language of transcription factors - MIT News Office

Deciphering the language of transcription factors - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it

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Larry Hardesty

"
Transcription factors are proteins that bind to DNA to promote or suppress protein production. Since almost all diseases involve disruption of the protein-production process, transcription factors are promising biological targets for drugs — and could even serve as drugs themselves.

But there are likely thousands of transcription factors in humans, each of which might bind to the genome at tens of thousands of different locations. Previously, there was no cost-effective way to figure out exactly where transcription factors bind — which exact DNA letters in a given stretch of genome each of them attaches to. Biologists thus relied on approximate methods to identify the general vicinity of binding sites.

In the August issue of the online journal PLoS Computational Biology, a team of researchers from MIT’s Computer Science and Artificial Intelligence Laboratory presented a new analytic technique that identifies binding sites with much greater accuracy. As a consequence, the researchers were able to infer previously unknown relationships among transcription factors, which could provide clues to the roles they play in biological processes.

The researchers initially tested their technique on two sets of experimental data, which they say represent both “relatively easy and difficult cases” for analysis. In the easy case, their new technique identified the precise locations at which transcription factors bound to the genome with more than 90 percent accuracy, while the accuracy of existing techniques was about 10 percent or less. In the difficult case, the new method was more than 55 percent accurate, compared to about 5 percent for existing techniques."
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iGEM Buenos Aires: Synthetic bacterial communities | Lab Rat, Scientific American Blog Network

iGEM Buenos Aires: Synthetic bacterial communities | Lab Rat, Scientific American Blog Network | SynBioFromLeukipposInstitute | Scoop.it
Each year, the iGEM competition encourages undergraduates from all over the world to create synthetic bacterial machines by organising modular pieces of genome. This is a ...
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Soapbox Science: A lesson from ENCODE about the limits on Human Reason : Soapbox Science

Soapbox Science: A lesson from ENCODE about the limits on Human Reason : Soapbox Science | SynBioFromLeukipposInstitute | Scoop.it
David Ropeik is an international consultant in risk perception and risk communication, and an Instructor in the Environmental Management Program at the Harvard University Extension School. He is the author of How Risky Is It, Really?
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A programmable NOR-based device for transcription profile analysis : Scientific Reports : Nature Publishing Group

A programmable NOR-based device for transcription profile analysis : Scientific Reports : Nature Publishing Group | SynBioFromLeukipposInstitute | Scoop.it

 

by
Tom Ran, Yehonatan Douek, Lilach Milo & Ehud Shapiro

"An autonomous synthetic programmable device that can diagnose a cell's state according to predefined markers and produce a corresponding therapeutic output may be the basis of future programmable drugs. Motivated to increase diagnosis precision, devices that integrate multiple disease markers have been implemented based on various molecular tools. As simplicity is key to future in-vivo applications, we sought a molecular device that a) integrates multiple inputs without requiring pairwise interactions, and b) harnesses only mechanisms that cells natively use. Here we show a synthetic NOR-based programmable device, operating via a biochemical obstructing approach rather than on a constructive approach, capable of differentiating between prokaryotic cell strains based on their unique expression profile. To demonstrate our system's strengths we further implemented the NOT, OR and AND gates. The device's programmability allows context-dependent selection of the inputs being sensed, and of the expressed output, thus, holding great promise in future biomedical applications."

http://bit.ly/Qswizi

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Fundamentals of Biology now available in OCW Scholar format - MIT News Office

Fundamentals of Biology now available in OCW Scholar format - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it

*Fundamentals of Biology now available in open course ware format - MIT*

"This Fundamentals of Biology course presents *six outstanding MIT professors* lecturing in their respective specialties. For example, Professor *Eric Lander* — perhaps best known as one of the principal leaders of the Human Genome Project, which mapped the genetic structure and sequence of human DNA — delivers a series of introductory lectures on genetics. The chance to hear each of these professors, many of them recognized as pioneers for their groundbreaking research, deliver course material drawn from their own area of expertise presents a unique opportunity for the independent learner."

http://bit.ly/Q9VxUY

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What do you know about Synthetic Biology?

What do you know about Synthetic Biology? | SynBioFromLeukipposInstitute | Scoop.it
We have published a quiz in order to know what people know and think about Synthetic Biology. Feel free to answer and spread it . If you want to answer it, please click the link that corresponds to...
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igemvalencia 2012's comment, September 8, 2012 11:34 AM
Thank you for publish it!
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Alexandra Daisy Ginsberg "I bring synthetic aesthetics and a biotechnological future "

Alexandra Daisy Ginsberg "I bring synthetic aesthetics and a biotechnological future " | SynBioFromLeukipposInstitute | Scoop.it

 http://bit.ly/Ogly8E

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*Evolutionary principles and synthetic biology*: avoiding a molecular tragedy of the commons with an engineered phage

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Gladstone E, Molineux I, Bull J.

"BACKGROUND: In prior work, adding a gene to phage T7 that degraded the host K1 capsule facilitated growth when plated on capsulated hosts. However, the transgenic protein (an endosialidase) is expressed as an exoenzyme, released from the cell at lysis but unattached to the phage particle. There is thus the possibility that the gene will be subject to a tragedy of the commons and be selected against, if the enzyme benefits other genomes. Results: This evolutionary perspective was supported in short term experiments. The genome carrying the endosialidase gene was favored on a capsulated host if grown in physical isolation of control genomes (lacking the gene) but was selected against otherwise. Conclusions: These results challenge efforts to engineer phages with exoenzymes that degrade biofilm polymers. If biofilms do not facilitate spatially structured phage growth, the transgenic enzymes may be rapidly eliminated from the phage population after release in the environment, even if the transgene benefits overall phage growth on the biofilm."

http://1.usa.gov/RfvnEk

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Journal of Biological Engineering | Abstract | The Constructor: a web application optimizing cloning strategies based on modules from the registry of standard biological parts

*The Constructor*

www.systemsbiology.nl/the_constructor

*a web app optimizing cloning strategies based on modules from the registry of standard biological parts*

by
Hesselman MC, Koehorst JJ, Slijkhuis T, Hugenholtz F, Odoni DI, van Passel MW.

"Synthetic biology is an emerging field that combines molecular biology with engineering principles, which requires abstraction levels applied to a modular biological componentry. The Registry of Standard Biological Parts harbours such a repository of standardized parts, and thereby facilitates the combination of complex molecular modules to novel genetic circuits and devices. However, since finding the best parts for a pre-determined genetic design can be time consuming, we devised the Constructor, a web tool that recommends the smallest number of cloning steps for pre-designed circuits, and implements user-defined quality checks.We present the Constructor (www.systemsbiology.nl/the_constructor) as a constructive web tool that simplifies the in silico assembly of pre-designed gene circuitries from standard parts, reducing both planning and subsequent cloning time.*

http://bit.ly/NOXTwi

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Nature ENCODE : Nature Publishing Group : A landmark in the understanding of the human genome

Nature ENCODE : Nature Publishing Group : A landmark in the understanding of the human genome | SynBioFromLeukipposInstitute | Scoop.it
Nature ENCODE: Explore the wealth of information about the project's key findings and numerous integrative analyses.
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New DNA Encyclopedia Attempts to Map Function of Entire Human Genome | Wired Science | Wired.com

New DNA Encyclopedia Attempts to Map Function of Entire Human Genome | Wired Science | Wired.com | SynBioFromLeukipposInstitute | Scoop.it
A torrent of new data charts the human genome in unprecedented detail, a landmark accomplishment compared by some scientists to the genome’s sequencing in 1999.
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ENCODE Project at UCSC

ENCODE Project at UCSC | SynBioFromLeukipposInstitute | Scoop.it

The Encyclopedia of DNA Elements (ENCODE) Consortium is an international collaboration of research groups funded by the National Human Genome Research Institute (NHGRI). The goal of ENCODE is to build a comprehensive parts list of functional elements in the human genome, including elements that act at the protein and RNA levels, and regulatory elements that control cells and circumstances in which a gene is active.

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Evolutionary principles and synthetic biology: avoiding a molecular tragedy of the commons with an engineered phage

by

Eric Gladstone, Ian Molineux and James Bull

"In prior work, adding a gene to phage T7 that degraded the host K1 capsule facilitated growth when plated on capsulated hosts. However, the transgenic protein (an endosialidase) is expressed as an exoenzyme, released from the cell at lysis but unattached to the phage particle. There is thus the possibility that the gene will be subject to a tragedy of the commons and be selected against, if the enzyme benefits other genomes. Results: This evolutionary perspective was supported in short term experiments. The genome carrying the endosialidase gene was favored on a capsulated host if grown in physical isolation of control genomes (lacking the gene) but was selected against otherwise. Conclusions: These results challenge efforts to engineer phages with exoenzymes that degrade biofilm polymers. If biofilms do not facilitate spatially structured phage growth, the transgenic enzymes may be rapidly eliminated from the phage population after release in the environment, even if the transgene benefits overall phage growth on the biofilm."

http://bit.ly/PatvcN

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Blinded by Big Science: The lesson I learned from ENCODE is that projects like ENCODE are not a good idea

By Michael Eisen

"When the draft sequence of the human genome was finished in 2001, the accomplishment was heralded as marking the dawn of the age of “big biology”. The high-throughput techniques and automation developed to sequence DNA on a massive scale would be wielded to generate not just genomes, but reference data sets in all areas of biomedicine.

The NHGRI moved quickly to expand the universe of sequenced genomes, and to catalog variation within the human population with HapMap, HapMap 2 and 1000 genomes. But they also began to dip their toe into the murkier waters of “functional genomics”, launching ENCODE, a grand effort to build an encyclopedia of functional elements in the human genome. The idea was to simultaneously annotate the human genome and provide basic and applied scientists working on human disease with reference data sets that they would otherwise have had to generate themselves. Instead of having to invest in expensive equipment and learn complex protocols, they would often be able to just download the results, thereby making everything they did faster and better...."

http://bit.ly/NWk0ks

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Designing and using RNA scaffolds to assemble proteins in vivo : Nature Protocols : Nature Publishing Group

Designing and using RNA scaffolds to assemble proteins in vivo : Nature Protocols : Nature Publishing Group | SynBioFromLeukipposInstitute | Scoop.it

by

Delebecque CJ, Silver PA, Lindner AB.

"RNA scaffolds are synthetic noncoding RNA molecules with engineered 3D folding harnessed to spatially organize proteins in vivo. Here we provide a protocol to design, express and characterize RNA scaffolds and their cognate proteins within 1 month. The RNA scaffold designs described here are based on either monomeric or multimeric units harboring RNA aptamers as protein docking sites. The scaffolds and proteins are cloned into inducible plasmids and expressed to form functional assemblies. RNA scaffolds find applications in many fields in which in vivo organization of biomolecules is of interest. RNA scaffolds provide extended flexibility compared with DNA or protein scaffolding strategies through programmed modulation of multiple protein stoichiometry and numbers, as well as the proteins' relative distances and spatial orientations. For synthetic biology, RNA scaffolds provide a new platform that can be used to increase yields of sequential metabolic pathways."
http://bit.ly/O3goHC

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Engineered cell-cell communication via DNA messaging

by

Monica E Ortiz and Drew Endy

"Background
Evolution has selected for organisms that benefit from genetically encoded cell-cell communication. Engineers have begun to repurpose elements of natural communication systems to realize programmed pattern formation and coordinate other population-level behaviors. However, existing engineered systems rely on system-specific small molecules to send molecular messages among cells. Thus, the information transmission capacity of current engineered biological communication systems is physically limited by specific biomolecules that are capable of sending only a single message, typically "regulate transcription."

Results
We have engineered a cell-cell communication platform using bacteriophage M13 gene products to autonomously package and deliver heterologous DNA messages of varying lengths and encoded functions. We demonstrate the decoupling of messages from a common communication channel via the autonomous transmission of various arbitrary genetic messages. Further, we increase the range of engineered DNA messaging across semisolid media by linking message transmission or receipt to active cellular chemotaxis.

Conclusions
We demonstrate decoupling of a communication channel from message transmission within engineered biological systems via the autonomous targeted transduction of user-specified heterologous DNA messages. We also demonstrate that bacteriophage M13 particle production and message transduction occurs among chemotactic bacteria. We use chemotaxis to improve the range of DNA messaging, increasing both transmission distance and communication bit rates relative to existing small molecule-based communication systems. We postulate that integration of different engineered cell-cell communication platforms will allow for more complex spatial programming of dynamic cellular consortia."
http://bit.ly/OgwS4N

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Essential genes as antimicrobial targets a... [Trends Biotechnol. 2012] - PubMed - NCBI

by

Juhas M, Eberl L, Church GM.

 

"Essential genes are absolutely required for the survival of any living entity. Investigation of essential genes is therefore expected to advance tremendously our understanding of the universal principles of life. Determination of a minimal set of essential genes needed to sustain life also plays an important role in the emerging field of synthetic biology, whose goals include creation of a stringently controlled minimal cell with predesigned phenotypic traits. In addition, due to their indispensability for survival of bacteria, genes encoding essential cellular functions have great potential in medicine as promising targets for the development of novel antimicrobials. Here, we review recent advances in the investigation of essential genes, with emphasis on the practical applications in medicine and synthetic biology."

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Researchers identify biochemical functions for most of the human genome - MIT News Office

Researchers identify biochemical functions for most of the human genome - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it

New map provides a reference for interpreting function of disease-associated regions.

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Genomics: ENCODE explained : Nature : Nature Publishing Group

Genomics: ENCODE explained : Nature : Nature Publishing Group | SynBioFromLeukipposInstitute | Scoop.it
The Encyclopedia of DNA Elements (ENCODE) project dishes up a hearty banquet of data that illuminate the roles of the functional elements of the human genome.
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Concept Artist Uses Yeast to Clone Lady Gaga, President Obama | Underwire | Wired.com

Concept Artist Uses Yeast to Clone Lady Gaga, President Obama | Underwire | Wired.com | SynBioFromLeukipposInstitute | Scoop.it
Want a big response for your art opening? It might not be a bad idea to put President Obama and Lady Gaga on display.
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De novo automated design of small RNA circuits for engineering synthetic riboregulation in living cells

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Rodrigo G, Landrain TE, Jaramillo A.

"A grand challenge in synthetic biology is to use our current knowledge of RNA science to perform the automatic engineering of completely synthetic sequences encoding functional RNAs in living cells. We report here a fully automated design methodology and experimental validation of synthetic RNA interaction circuits working in a cellular environment. The computational algorithm, based on a physicochemical model, produces novel RNA sequences by exploring the space of possible sequences compatible with predefined structures. We tested our methodology in Escherichia coli by designing several positive riboregulators with diverse structures and interaction models, suggesting that only the energy of formation and the activation energy (free energy barrier to overcome for initiating the hybridization reaction) are sufficient criteria to engineer RNA interaction and regulation in bacteria. The designed sequences exhibit nonsignificant similarity to any known noncoding RNA sequence. Our riboregulatory devices work independently and in combination with transcription regulation to create complex logic circuits. Our results demonstrate that a computational methodology based on first-principles can be used to engineer interacting RNAs with allosteric behavior in living cells."

http://bit.ly/Q7CASI

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Ewan's Blog; bioinformatician at large: ENCODE: My own thoughts

Ewan's Blog; bioinformatician at large: ENCODE: My own thoughts | SynBioFromLeukipposInstitute | Scoop.it
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2012 Release: ENCODE data describes function of human genome

2012 Release: ENCODE data describes function of human genome | SynBioFromLeukipposInstitute | Scoop.it

ENCODE data describes function of human genome

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