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Craig Venter Tackle Aging

Craig Venter Tackle Aging | SynBioFromLeukipposInstitute | Scoop.it
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MAGGIE FOX
"Craig Venter, who managed to make science both lucrative and glamorous with his pioneering approach to gene sequencing and synthetic biology, is taking on a new venture: aging.
He has joined forces with the founder of the X Prize and an expert in cell therapy to launch on Tuesday a new company called Human Longevity Inc. The man who once took off on his personal yacht to sample all the microscopic life in the seas plans to leverage some of the most fashionable new scientific approaches to figure out what makes us sick and old.
The San Diego-based company will tackle aging using gene sequencing; stem cell approaches; the collection of bacteria and other life forms that live in and on us called the microbiome; and the metabolome, which includes the byproducts of life called metabolites.
They’ll start out with what they are calling the largest human sequencing operation in the world.
“We are building a lab to a scale never attempted (before),” Venter told NBC News.
Venter first shot to fame when he raced with government scientists to finish the first map of all human DNA, called the human genome. Venter, himself a former government scientist, annoyed his former colleagues with a brash new approach to gene sequencing that was much faster but far less accurate, in their opinion.
“We are building a lab to a scale never attempted (before).”
The two teams joined forces, the partnership worked, and they finished their first draft in 2001.
Venter later parted ways with the company he founded to sequence genes and went on to tackle other challenges, including a venture that included weeks on his personal yacht sequencing the DNA of microbial life in the ocean.
He also took a crack at creating artificial life, making a synthetic bacterium of sorts, and making more controversy with that.
For the new company, Venter is teaming up Dr. Robert Hariri, who directs cell therapy operations at Celgene, a biopharmaceutical company, and engineer Dr. Peter Diamandis, chairman of the X Prize Foundation. Karen Nelson, who headed the J. Craig Venter Institute (JCVI), will lead the microbiome team.
Studies — including projects at JCVI — have shown the bacteria, fungi and other creatures living in and on the human body affect diseases from cancer to eczema and dandruff. Hariri says their byproducts may also affect how well we age. “If you eliminate these various diseases, you eliminate the things contributing to unhealthy aging,” Hariri said.
"We believe the key to … make 100 the new 60, is something well within our grasp.”
Stem cells, the body’s master cells, secrete compounds that affect tissues and may be able to turn back the clock on some diseases associated with aging, he added.
It’s just a good time to tackle these kinds of projects, said Diamandis. The science is there, for one. “There is also this explosion of massive computational power,” said Diamandis, whose first X Prize challenge offered $10 million in 1996 to inspire commercial space ventures. (Burt Rutan won in 2004 with SpaceShipOne, a piloted rocket plane.)
“The time for creating extended high-performing humans genetically is now. We believe the key to … make 100 the new 60, is something well within our grasp.”
The new company doesn’t aim to extend human life so much as to help keep people healthy as they get older.
“The challenge is when you live into your 80s, 90s, to 100, living in a way that is decrepit and old is of zero value,” Diamandis said.
So, the goal is to battle all the diseases of aging, Venter said.
Is there a magic number? “I am hoping it is bigger than 68,” joked Venter, who is 67..."
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Introduction of a Synthetic CO2-Fixing Photorespiratory Bypass into a Cyanobacterium

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Patrick M. Shi1, Jan Zarzycki, Krishna K. Niyogi and Cheryl A. Kerfeld

"Global photosynthetic productivity is limited by the enzymatic assimilation of CO2 into organic carbon compounds. Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), the carboxylating enzyme of the Calvin-Benson (CB) cycle, poorly discriminates between CO2 and O2, leading to photorespiration and the loss of fixed carbon and nitrogen. With the advent of synthetic biology, it is now feasible to design, synthesize and introduce biochemical pathways in vivo. We engineered a synthetic photorespiratory bypass based on the 3-hydroxypropionate bi-cycle into the model cyanobacterium, Synechococcus elongatus sp. PCC 7942. The heterologously expressed cycle is designed to function as both a photorespiratory bypass and an additional CO2-fixing pathway, supplementing the CB cycle. We demonstrate the function of all six introduced enzymes and identify bottlenecks to be targeted in subsequent bioengineering. These results have implications for efforts to improve photosynthesis, and for the "green" production of high-value products of biotechnological interest."

 http://bit.ly/1kvbwPS

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Fluorescent in situ sequencing

George Church, Ph.D., a Core Faculty member at the Wyss Institute and Professor of Genetics at Harvard Medical School, explains how fluorescent in situ sequencing…
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Nanotube twins - Coupled carbon and peptide nanotubes achieved for the first time

Nanotube twins - Coupled carbon and peptide nanotubes achieved for the first time | SynBioFromLeukipposInstitute | Scoop.it
Nanotube twins - Coupled carbon and peptide nanotubes achieved for the first time
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James Collins Podcast: Quantitative Approaches to Genetic Networks

James Collins Podcast: Quantitative Approaches to Genetic Networks | SynBioFromLeukipposInstitute | Scoop.it
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 http://bit.ly/1mO1fwx

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A computational pipeline for identifying kinetic motifs to aid in the design and improvement of synthetic gene circuits

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Chiang AW, Hwang MJ.

"An increasing number of genetic components are available in several depositories of such components to facilitate synthetic biology research, but picking out those that will allow a designed circuit to achieve the specified function still requires multiple cycles of testing. Here, we addressed this problem by developing a computational pipeline to mathematically simulate a gene circuit for a comprehensive range and combination of the kinetic parameters of the biological components that constitute the gene circuit.

RESULTS:
We showed that, using a well-studied transcriptional repression cascade as an example, the sets of kinetic parameters that could produce the specified system dynamics of the gene circuit formed clusters of recurrent combinations, referred to as kinetic motifs, which appear to be associated with both the specific topology and specified dynamics of the circuit. Furthermore, the use of the resulting "handbook" of performance-ranked kinetic motifs in finding suitable circuit components was illustrated in two application scenarios.
CONCLUSIONS:
These results show that the computational pipeline developed here can provide a rational-based guide to aid in the design and improvement of synthetic gene circuits."



 http://bit.ly/1frVPa2

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Synthetic biology as it relates to CAM photosynthesis: challenges and opportunities

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Depaoli HC, Borland AM, Tuskan GA, Cushman JC, Yang X.

"To meet future food and energy security needs, which are amplified by increasing population growth and reduced natural resource availability, metabolic engineering efforts have moved from manipulating single genes/proteins to introducing multiple genes and novel pathways to improve photosynthetic efficiency in a more comprehensive manner. Biochemical carbon-concentrating mechanisms such as crassulacean acid metabolism (CAM), which improves photosynthetic, water-use, and possibly nutrient-use efficiency, represent a strategic target for synthetic biology to engineer more productive C3 crops for a warmer and drier world. One key challenge for introducing multigene traits like CAM onto a background of C3 photosynthesis is to gain a better understanding of the dynamic spatial and temporal regulatory events that underpin photosynthetic metabolism. With the aid of systems and computational biology, vast amounts of experimental data encompassing transcriptomics, proteomics, and metabolomics can be related in a network to create dynamic models. Such models can undergo simulations to discover key regulatory elements in metabolism and suggest strategic substitution or augmentation by synthetic components to improve photosynthetic performance and water-use efficiency in C3 crops. Another key challenge in the application of synthetic biology to photosynthesis research is to develop efficient systems for multigene assembly and stacking. Here, we review recent progress in computational modelling as applied to plant photosynthesis, with attention to the requirements for CAM, and recent advances in synthetic biology tool development. Lastly, we discuss possible options for multigene pathway construction in plants with an emphasis on CAM-into-C3 engineering."
http://bit.ly/1o6oPUg

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The synthetic biology future.

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Sleator RD.

"Herein, I track the evolution of synthetic biology from its earliest incarnations more than 50 years ago, through the DIYbio revolution, to the next 50 years."


 http://1.usa.gov/1o3EcwH

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Bob's curator insight, April 15, 2014 12:50 PM

About synthetic biology

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CSHAsia 2014 Conference on Synthetic Biology

CSHAsia 2014 Conference on Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
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COLD SPRING HARBOR ASIA CONFERENCES: Synthetic Biology - Suzhou, China

December 1-5, 2014 http://bit.ly/MUVtN4

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Engineering reduced evolutionary potential for synthetic biology

Engineering reduced evolutionary potential for synthetic biology | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Renda BA, Hammerling MJ, Barrick JE.

"The field of synthetic biology seeks to engineer reliable and predictable behaviors in organisms from collections of standardized genetic parts. However, unlike other types of machines, genetically encoded biological systems are prone to changes in their designed sequences due to mutations in their DNA sequences after these devices are constructed and deployed. Thus, biological engineering efforts can be confounded by undesired evolution that rapidly breaks the functions of parts and systems, particularly when they are costly to the host cell to maintain. Here, we explain the fundamental properties that determine the evolvability of biological systems. Then, we use this framework to review current efforts to engineer the DNA sequences that encode synthetic biology devices and the genomes of their microbial hosts to reduce their ability to evolve and therefore increase their genetic reliability so that they maintain their intended functions over longer timescales."

http://rsc.li/1f6qTMi

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Synthetic Biology Market is Expected to Reach USD 16.7 Billion Globally in 2018

Synthetic Biology Market is Expected to Reach USD 16.7 Billion Globally in 2018 | SynBioFromLeukipposInstitute | Scoop.it
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Artificial Riboswitch Selection: A FACS-Based Approach

Artificial Riboswitch Selection: A FACS-Based Approach | SynBioFromLeukipposInstitute | Scoop.it
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by
Zohaib Ghazi, Casey C. Fowler, Yingfu Li

"Riboswitches have a number of characteristics that make them ideal regulatory elements for a wide range of synthetic biology applications. To maximize their utility, methods are required to create custom riboswitches de novo or to modify existing riboswitches to suit specific experimental needs. This chapter describes such a method, which exploits fluorescence-activated cell sorting (FACS) to quickly and efficiently sort through large libraries of riboswitch-like sequences to identify those with the desired activity. Suggestions for the experimental setup are provided, along with detailed protocols for testing and optimizing FACS conditions FACS selection steps, and follow-up assays to identify and characterize individual riboswitches."

http://bit.ly/1bqtoZa

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In Vivo Screening for Aptazyme-Based Bacterial Riboswitches

In Vivo Screening for Aptazyme-Based Bacterial Riboswitches | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Rehm C, Hartig JS.

"In many synthetic biology applications, modular and easily accessible tools for controlling gene expression are required. In addition, in vivo biosensors and diagnostic devices will become more important in the future to allow for noninvasive determination of protein, ion, or small molecule metabolite levels. In recent years synthetic RNA-based switches have been developed to act as signal transducers to convert a binding event of a small molecule (input) into a detectable output. Their modular design allows the development of a variety of molecular switches to be used in biochemical assays or inside living cells. RNA switches developed by our group are based on the Schistosoma mansoni hammerhead ribozyme, a self-cleaving RNA sequence that can be inserted into any RNA of interest. Connection to an aptamer sensing a small molecule renders the cleavage reaction ligand-dependent. In the past we have successfully designed and applied such hammerhead aptazymes for the allosteric control of both bacterial and eukaryotic gene expression by affecting transcription elongation, translation initiation, or mRNA stability. In order to yield functional switches optimization of the connecting sequence between the aptamer and the HHR needs to be carried out. We have therefore developed an in vivo screening protocol detailed in this chapter that allows the identification of functional aptazymes in bacteria."

http://bit.ly/1jTaL2Q

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How to Make a Synthetic Multicellular Computer

How to Make a Synthetic Multicellular Computer | SynBioFromLeukipposInstitute | Scoop.it
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Macia J, Sole R

"Biological systems perform computations at multiple scales and they do so in a robust way. Engineering metaphors have often been used in order to provide a rationale for modeling cellular and molecular computing networks and as the basis for their synthetic design. However, a major constraint in this mapping between electronic and wet computational circuits is the wiring problem. Although wires are identical within electronic devices, they must be different when using synthetic biology designs. Moreover, in most cases the designed molecular systems cannot be reused for other functions. A new approximation allows us to simplify the problem by using synthetic cellular consortia where the output of the computation is distributed over multiple engineered cells. By evolving circuits in silico, we can obtain the minimal sets of Boolean units required to solve the given problem at the lowest cost using cellular consortia. Our analysis reveals that the basic set of logic units is typically non-standard. Among the most common units, the so called inverted IMPLIES (N-Implies) appears to be one of the most important elements along with the NOT and AND functions. Although NOR and NAND gates are widely used in electronics, evolved circuits based on combinations of these gates are rare, thus suggesting that the strategy of combining the same basic logic gates might be inappropriate in order to easily implement synthetic computational constructs. The implications for future synthetic designs, the general view of synthetic biology as a standard engineering domain, as well as potencial drawbacks are outlined."


http://bit.ly/NseMxD

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Bob's curator insight, April 15, 2014 12:51 PM

synthetic multicellular computer

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Fungal extrolites as a new source for therapeutic compounds and as building blocks for applications in synthetic biology

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Ana Lúcia Leitãoa,  Francisco J. Enguita

"Secondary metabolic pathways of fungal origin provide an almost unlimited resource of new compounds for medical applications, which can fulfill some of the, currently unmet, needs for therapeutic alternatives for the treatment of a number of diseases. Secondary metabolites secreted to the extracellular medium (extrolites) belong to diverse chemical and structural families, but the majority of them are synthesized by the condensation of a limited number of precursor building blocks including amino acids, sugars, lipids and low molecular weight compounds also employed in anabolic processes. In fungi, genes related to secondary metabolic pathways are frequently clustered together and show a modular organization within fungal genomes. The majority of fungal gene clusters responsible for the biosynthesis of secondary metabolites contain genes encoding a high molecular weight condensing enzyme which is responsible for the assembly of the precursor units of the metabolite. They also contain other auxiliary genes which encode enzymes involved in subsequent chemical modification of the metabolite core. Synthetic biology is a branch of molecular biology whose main objective is the manipulation of cellular components and processes in order to perform logically connected metabolic functions. In synthetic biology applications, biosynthetic modules from secondary metabolic processes can be rationally engineered and combined to produce either new compounds, or to improve the activities and/or the bioavailability of the already known ones. Recently, advanced genome editing techniques based on guided DNA endonucleases have shown potential for the manipulation of eukaryotic and bacterial genomes. This review discusses the potential application of genetic engineering and genome editing tools in the rational design of fungal secondary metabolite pathways by taking advantage of the increasing availability of genomic and biochemical data."


http://bit.ly/NsbMRQ

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Synthetic Aesthetics: Investigating Synthetic Biology's Designs on Nature: Alexandra Daisy Ginsberg, Jane Calvert, Pablo Schyfter, Alistair Elfick, Drew Endy: 9780262019996: Amazon.com: Books

Synthetic Aesthetics: Investigating Synthetic Biology's Designs on Nature

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mRNA translation and protein synthesis: an analysis of different modelling methodologies and a new PBN based approach

mRNA translation involves simultaneous movement of multiple ribosomes on the mRNA and is also subject to regulatory mechanisms at different stages. Translation can be described by various codon-based models, including ODE, TASEP, and Petri net models. Although such models have been extensively used, the overlap and differences between these models and the implications of the assumptions of each model has not been systematically elucidated. The selection of the most appropriate modelling framework, and the most appropriate way to develop coarse-grained/fine-grained models in different contexts is not clear.
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The Mammoth Cometh

The Mammoth Cometh | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

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ATHANIEL RICH

"The first time Ben Novak saw a passenger pigeon, he fell to his knees and remained in that position, speechless, for 20 minutes. He was 16. At 13, Novak vowed to devote his life to resurrecting extinct animals. At 14, he saw a photograph of a passenger pigeon in an Audubon Society book and “fell in love.” But he didn’t know that the Science Museum of Minnesota, which he was then visiting with a summer program for North Dakotan high-school students, had them in their collection, so he was shocked when he came across a cabinet containing two stuffed pigeons, a male and a female, mounted in lifelike poses. He was overcome by awe, sadness and the birds’ physical beauty: their bright auburn breasts, slate-gray backs and the dusting of iridescence around their napes that, depending on the light and angle, appeared purple, fuchsia or green. Before his chaperones dragged him out of the room, Novak snapped a photograph with his disposable camera. The flash was too strong, however, and when the film was processed several weeks later, he was haunted to discover that the photograph hadn’t developed. It was blank, just a flash of white light.

In the decade since, Novak has visited 339 passenger pigeons — at the Burke Museum in Seattle, the Carnegie Museum of Natural History in Pittsburgh, the American Museum of Natural History in New York and Harvard’s Ornithology Department, which has 145 specimens, including eight pigeon corpses preserved in jars of ethanol, 31 eggs and a partly albino pigeon. There are 1,532 passenger-pigeon specimens left on Earth. On Sept. 1, 1914, Martha, the last captive passenger pigeon, died at the Cincinnati Zoo. She outlasted George, the penultimate survivor of her species and her only companion, by four years. As news spread of her species’ imminent extinction, Martha became a minor tourist attraction. In her final years, whether depressed or just old, she barely moved. Underwhelmed zoo visitors threw fistfuls of sand at her to elicit a reaction. When she finally died, her body was taken to the Cincinnati Ice Company, frozen in a 300-pound ice cube and shipped by train to the Smithsonian Institution, where she was stuffed and mounted and visited, 99 years later, by Ben Novak.
The fact that we can pinpoint the death of the last known passenger pigeon is one of many peculiarities that distinguish the species. Many thousands of species go extinct every year, but we tend to be unaware of their passing, because we’re unaware of the existence of most species. The passenger pigeon’s decline was impossible to ignore, because as recently as the 1880s, it was the most populous vertebrate in North America. It made up as much as 40 percent of the continent’s bird population. In “A Feathered River Across the Sky,” Joel Greenberg suggests that the species’ population “may have exceeded that of every other bird on earth.” In 1860, a naturalist observed a single flock that he estimated to contain 3,717,120,000 pigeons. By comparison, there are currently 260 million rock pigeons in existence. A single passenger-pigeon nesting ground once occupied an area as large as 850 square miles, or 37 Manhattans.
The species’ incredible abundance was an enticement to mass slaughter. The birds were hunted for their meat, which was sold by the ton (at the higher end of the market, Delmonico’s served pigeon cutlets); for their oil and feathers; and for sport. Even so, their rapid decline — from approximately five billion to extinction within a few decades — baffled most Americans. Science magazine published an article claiming that the birds had all fled to the Arizona desert. Others hypothesized that the pigeons had taken refuge in the Chilean pine forests or somewhere east of the Puget Sound or in Australia. Another theory held that every passenger pigeon had joined a single megaflock and disappeared into the Bermuda Triangle...."



http://nyti.ms/1csjod1

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Analog synthetic biology

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by
Sarpeshkar R.

"We analyse the pros and cons of analog versus digital computation in living cells. Our analysis is based on fundamental laws of noise in gene and protein expression, which set limits on the energy, time, space, molecular count and part-count resources needed to compute at a given level of precision. We conclude that analog computation is significantly more efficient in its use of resources than deterministic digital computation even at relatively high levels of precision in the cell. Based on this analysis, we conclude that synthetic biology must use analog, collective analog, probabilistic and hybrid analog-digital computational approaches; otherwise, even relatively simple synthetic computations in cells such as addition will exceed energy and molecular-count budgets. We present schematics for efficiently representing analog DNA-protein computation in cells. Analog electronic flow in subthreshold transistors and analog molecular flux in chemical reactions obey Boltzmann exponential laws of thermodynamics and are described by astoundingly similar logarithmic electrochemical potentials. Therefore, cytomorphic circuits can help to map circuit designs between electronic and biochemical domains. We review recent work that uses positive-feedback linearization circuits to architect wide-dynamic-range logarithmic analog computation in Escherichia coli using three transcription factors, nearly two orders of magnitude more efficient in parts than prior digital implementations."

http://1.usa.gov/1dA9Lcp

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Don't Get Hung Up On Gene Synthesis

Don't Get Hung Up On Gene Synthesis | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Markus Gershater

"Synthetic biology is a new field, but it sometimes feels like we already have dogma.  The idea that de novo DNA synthesis costs are limiting seems so ingrained: many of the major news stories we hear in synthetic biology are the latest milestones of ever larger chunks of DNA being stitched together, ever increasing numbers of strains being created, and the cost of DNA synthesis falling exponentially. There’s no doubt that the advances to date have been phenomenal, and I certainly tell anyone who gives me half a chance about how processes that took months when I was a PhD student can now be solved in minutes (and it really wasn’t that long ago).  The problem is, I’m not sure our attitudes have kept up with this pace of change: it’s the thesis of this post that due to these immensely rapid advances, DNA synthesis is no longer such an issue and we should now focus as a community on the bigger problem of effectively addressing biological complexity.

There are two reasons why we might need to make more DNA than is economic at the moment: either to make more constructs, or larger ones. 
Larger constructs
The fundamental issue with building larger constructs (e.g. >50 kilobases, or kb) is that you need the knowledge to be able to make such larger and more complex constructs work.  So either you need full knowledge of how dozens of biological parts will work together (or not) or you resort to copying large chunks from what you know works in nature (or all of it).  Therefore, the main limitation on making larger and more complex synthetic biology constructs is not the DNA synthesis, but our knowledge of what to do with that DNA synthesis.  Fundamentally, life is too complex and unpredictable for us to productively utilize large, engineered constructs at this point in our knowledge of biology.  We can make great advances with DNA that can directly and easily be assembled from small building blocks, and along the way develop the tools that will allow us to truly engineer the more ambitious systems that will need larger constructs....."


 http://bit.ly/MZ7lhd

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Open questions in origin of life: experimental studies on the origin of nucleic acids and proteins with specific and functional sequences by a chemical synthetic biology approach

Open questions in origin of life: experimental studies on the origin of nucleic acids and proteins with specific and functional sequences by a chemical synthetic biology approach | SynBioFromLeukipposInstitute | Scoop.it
Open questions in origin of life: experimental studies on the origin of nucleic acids and proteins with specific and functional sequences by a chemical synthetic biology approach
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What is synthetic biology and why does it matter? - CISAC

What is synthetic biology and why does it matter? - CISAC | SynBioFromLeukipposInstitute | Scoop.it
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Drew Endy today at Stanford 11.30 am: What is synthetic biology and why does it matter? http://stanford.io/1fNZnyl

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TEDxVilnius - TEDxVilnius 2014 Simulcast

TEDxVilnius 2014: THE FUTURE IS OURS - Feb 22nd, Saturday, Theatre Arena, Olimpieciu str. 3
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Human Biology Hacker Sean Ward on stage "How Synthetic Biology Is Exploring Biological Complexity http://bit.ly/1egbTFH

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MIT’s Synthetic Biology Center collaborates with Pfizer to advance synthetic biology research in drug discovery and development - MIT News Office

MIT’s Synthetic Biology Center collaborates with Pfizer to advance synthetic biology research in drug discovery and development - MIT News Office | SynBioFromLeukipposInstitute | Scoop.it
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Generation of Orthogonally Selective Bacterial Riboswitches by Targeted Mutagenesis and In Vivo Screening

Generation of Orthogonally Selective Bacterial Riboswitches by Targeted Mutagenesis and In Vivo Screening | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Vincent HA, Robinson CJ, Wu MC, Dixon N, Micklefield J.

"Riboswitches are naturally occurring RNA-based genetic switches that control gene expression in response to the binding of small-molecule ligands, typically through modulation of transcription or translation. Their simple mechanism of action and the expanding diversity of riboswitch classes make them attractive targets for the development of novel gene expression tools. The essential first step in realizing this potential is to generate artificial riboswitches that respond to nonnatural, synthetic ligands, thereby avoiding disruption of normal cellular function. Here we describe a strategy for engineering orthogonally selective riboswitches based on natural switches. The approach begins with saturation mutagenesis of the ligand-binding pocket of a naturally occurring riboswitch to generate a library of riboswitch mutants. These mutants are then screened in vivo against a synthetic compound library to identify functional riboswitch-ligand combinations. Promising riboswitch-ligand pairs are then further characterized both in vivo and in vitro. Using this method, a series of artificial riboswitches can be generated that are versatile synthetic biology tools for use in protein production, gene functional analysis, metabolic engineering, and other biotechnological applications."

 http://bit.ly/1jTc8P0

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