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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
Gerd Moe-Behrens's insight:

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

Illustration
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:

by
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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Synthesizing Biomolecule-Based Boolean Logic Gates

Synthesizing Biomolecule-Based Boolean Logic Gates | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:


by
Takafumi Miyamoto, Shiva Razavi, Robert DeRose, and Takanari Inoue

"One fascinating recent avenue of study in the

field of synthetic biology is the creation of biomolecule-basedcomputers. The main components of a computing deviceconsist of an arithmetic logic unit, the control unit, memory,and the input and output devices. Boolean logic gates are at thecore of the operational machinery of these parts, and hence tomake biocomputers a reality, biomolecular logic gates becomea necessity. Indeed, with the advent of more sophisticatedbiological tools, both nucleic acid- and protein-based logic systems have been generated. These devices function in the context of either test tubes or living cells and yield highly specific outputs given a set of inputs. In this review, we discuss various types of biomolecular logic gates that have been synthesized, with particular emphasis on recent developments that promise increased complexity of logic gate circuitry, improved computational speed, and potential clinical applications."



http://bit.ly/ZbHwem

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Synthetic biology: Stanford, UC Berkeley engineering a new frontier

Synthetic biology: Stanford, UC Berkeley engineering a new frontier | SynBioFromLeukipposInstitute | Scoop.it
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by

By Lisa M. Krieger


"Most people look at the cedar in Drew Endy's front yard and admire its graceful green boughs, heavy with needles, sap and cones.

Endy sees something much different: an industrial manufacturing platform, waiting to be exploited."I dream we could someday reprogram trees that could self-assemble a computer chip in your front yard," exudes the brilliant and intense Stanford University scientist, who has emerged as a leading evangelist in the new field of synthetic biology.One gene at a time, Endy and other elite teams of Bay Area scientists are striving to design and build organisms unlike anything made by Mother Nature.It's not yet possible to create artificial life from scratch. But it's getting closer, through projects that essentially swap out a cell's original operating system for a lab-designed one. These made-to-order creations then can be put to work.The Human Genome Project gave us the ability to read nature's instruction manual -- DNA -- like words in a book. But the real opportunities, scientists say, lie in our ability to not only read genetic code, but to write it, then build it using off-the-shelf chemical ingredients, strung together like holiday lights. It is the creation of new genomes -- and a new frontier in bioengineering.Synthetic biology works because biological creatures are, in essence, programmable manufacturing systems. The DNA instruction manual buried inside every cell -- its software, in a sense -- can be replaced with a man-made version, giving us the ability to tell it what to make.This presages the distant day when Endy's big Menlo Park cedar churns out computer chips, not cones. Or makes cancer-fighting drugs. Or fuels. Or building materials. Or anything else.There are concerns about safety and ethics. In the wrong hands, lone villains or rogue regimes could unleash dangerous life forms. A review in 2010 by a White House commission concluded the field needs monitoring, but the risks are still limited."

http://bit.ly/YzEQ87

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Growth-rate-dependent dynamics of a bacterial genetic oscillator

Growth-rate-dependent dynamics of a bacterial genetic oscillator | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Osella M, Lagomarsino MC.

"Gene networks exhibiting oscillatory dynamics are widespread in biology. The minimal regulatory designs giving rise to oscillations have been implemented synthetically and studied by mathematical modeling. However, most of the available analyses generally neglect the coupling of regulatory circuits with the cellular "chassis" in which the circuits are embedded. For example, the intracellular macromolecular composition of fast-growing bacteria changes with growth rate. As a consequence, important parameters of gene expression, such as ribosome concentration or cell volume, are growth-rate dependent, ultimately coupling the dynamics of genetic circuits with cell physiology. This work addresses the effects of growth rate on the dynamics of a paradigmatic example of genetic oscillator, the repressilator. Making use of empirical growth-rate dependencies of parameters in bacteria, we show that the repressilator dynamics can switch between oscillations and convergence to a fixed point depending on the cellular state of growth, and thus on the nutrients it is fed. The physical support of the circuit (type of plasmid or gene positions on the chromosome) also plays an important role in determining the oscillation stability and the growth-rate dependence of period and amplitude. This analysis has potential application in the field of synthetic biology, and suggests that the coupling between endogenous genetic oscillators and cell physiology can have substantial consequences for their functionality."
http://bit.ly/Zi1wQ6


In this connection some interesting piece of history:
"Shortly after François Jacob and Jacques Monod developed their first model of gene regulation, Goodwin proposed the first model of a genetic oscillator, showing that regulatory interactions among genes allowed periodic fluctuations to occur. Shortly after this model became published, he also formulated a general theory of complex gene regulatory networks using statistical mechanics. In its simplest form, Goodwin's oscillator involves a single gene that represses itself. Goodwin equations were originally formulated in terms of conservative (Hamiltonian) systems, thus not taking into account dissipative effects that are required in a realistic approach to regulatory phenomena in biology. Many versions have been developed since then. The simplest (but realistic) formulation considers three variables, X, Y and Z indicating the concentrations of RNA, protein and end product which generates the negative feedback loop.The equations are (see fig below) 
and closed oscillations can occur for n>8 and behave limit cycles: after a perturbation of the system's state, it returns to its previous attractor. A simple modification of this model, adding other terms introducing additional steps in the transcription machinery allows to find oscillations for smaller n values. Goodwin's model and its extensions have been widely used over the years as the basic skeleton for other models of oscillatory behavior, including circadian clocks, cell division or physiological control systems."
http://bit.ly/14YpWxz

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A Heritable Recombination System for Synthetic Darwinian Evolution in Yeast

A Heritable Recombination System for Synthetic Darwinian Evolution in Yeast | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Dante W. Romanini , Pamela Peralta-Yahya , Vanessa Mondol , and Virginia W. Cornish 

"Genetic recombination is central to the generation of molecular diversity and enhancement of evolutionary fitness in living systems. Methods such as DNA shuffling that recapitulate this diversity mechanism in vitro are powerful tools for engineering biomolecules with useful new functions by directed evolution. Synthetic biology now brings demand for analogous technologies that enable the controlled recombination of beneficial mutations in living cells. Thus, here we create a Heritable Recombination system centered around a library cassette plasmid that enables inducible mutagenesis via homologous recombination and subsequent combination of beneficial mutations through sexual reproduction in Saccharomyces cerevisiae. Using repair of nonsense codons in auxotrophic markers as a model, Heritable Recombination was optimized to give mutagenesis efficiencies of up to 6% and to allow successive repair of different markers through two cycles of sexual reproduction and recombination. Finally, Heritable Recombination was employed to change the substrate specificity of a biosynthetic enzyme, with beneficial mutations in three different active site loops crossed over three continuous rounds of mutation and selection to cover a total sequence diversity of 1013. Heritable Recombination, while at an early stage of development, breaks the transformation barrier to library size and can be immediately applied to combinatorial crossing of beneficial mutations for cell engineering, adding important features to the growing arsenal of next generation molecular biology tools for synthetic biology."

http://bit.ly/ZhYrzI

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Data barriers limit genetic diagnosis

Data barriers limit genetic diagnosis | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Erika Check Hayden

"Tools for data-sharing promise to improve chances of connecting mutations with symptoms of rare diseases.

For the first five months of Harrison Harkins’ life, doctors had little idea about what was causing his spinal malformation and inability to gain weight. But in November 2011, Matthew Bainbridge, a computational biologist at Baylor College of Medicine in Houston, Texas, found a clue. After analysing genetic data from Harrison and his parents, Bainbridge discovered that the child had an abnormal version of a gene called ASXL3. But Bainbridge had no easy access to records of other children with ASXL3 mutations, and could not be sure that this mutation was the culprit. So he did what many scientists do: he networked. A Dutch team put Bainbridge in touch with German researchers who were treating another boy with an ASXL3 mutation — and symptoms similar to Harrison’s. After finding two further cases in an internal Baylor database, Bainbridge felt that the connection was concrete. He describes the syndrome seen in all four children, and probably caused by ASXL3 mutations, in a paper published on 5 February (M. N. Bainbridge et al. Genome Med. 5, 11; 2013)....."

http://bit.ly/14WYXCx

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Multiplex Genome Engineering Using CRISPR/Cas Systems

Multiplex Genome Engineering Using CRISPR/Cas Systems | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Le Cong, F. Ann Ran, David Cox, Shuailiang Lin, Robert Barretto, Naomi Habib, Patrick D. Hsu, Xuebing Wu, Wenyan Jiang, Luciano A. Marraffini, Feng Zhang

"Functional elucidation of causal genetic variants and elements requires precise genome editing technologies. The type II prokaryotic CRISPR (clustered regularly interspaced short palindromic repeats)/Cas adaptive immune system has been shown to facilitate RNA-guided site-specific DNA cleavage. We engineered two different type II CRISPR/Cas systems and demonstrate that Cas9 nucleases can be directed by short RNAs to induce precise cleavage at endogenous genomic loci in human and mouse cells. Cas9 can also be converted into a nicking enzyme to facilitate homology-directed repair with minimal mutagenic activity. Lastly, multiple guide sequences can be encoded into a single CRISPR array to enable simultaneous editing of several sites within the mammalian genome, demonstrating easy programmability and wide applicability of the RNA-guided nuclease technology."

 http://bit.ly/VVv3yb

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Synthetic Biologists Make First Steps Toward Biological Computers

Synthetic Biologists Make First Steps Toward Biological Computers | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:


by
Joann Fan 

"Synthetic biology is a field that began more than a decade ago when James Collins, a synthetic biologist at Boston University in Massechusetts developed a genetic 'toggle switch.' He activated the switch in Escherichia coli cells, which are harmless bacteria found in the intestinal tract, and in 2009 he and several others developed a synthetic gene network that could count various user-defined inputs.

This week, Timothy Lu, who worked with Collins in 2009, published a paper in this week's Nature Biotechnology describing the process of altering cells into being able to respond to the 16 binary logic functions (boolean operators such as true, false, and, not, or, etc.). This research takes biology another step closer to electrical engineering, allowing scientists to, someday, encode even more complex computations into cells."We wanted to show you can assemble a bunch of simple parts in a very easy fashion to give you many types of logical functions," Lu, who led the research, told Nature. He and his team developed 16 plasmids (circular strings of DNA) - one for each of the boolean functions - and inserted them into the E. coli cells.Each plasmid type has a promoter and terminator DNA sequence, which regulates gene transcription (the first step in gene expression, where a segment of DNA is copied onto RNA), as well as an 'output gene' that triggers the production of a green glowing protein.You can think of the plasmid as the switch in a logic circuitboard. When certain conditions are fulfilled, it will either transcribe or fail to transcribe the output gene (in this case, green flourescence). "An electric 'AND' gate," which Nature uses as its example, "only gives a positive output when voltage is applied to both inputs." In an electric 'OR' gate, voltage can be applied to either gate, but not both to produce a positive output.In the genetic version of an 'AND' gate, two terminator sequences between the start and the finish must be neutralized by specific kinds of signal enzymes called recombinase, which can snip and rearrange the controller genes, before the output will be transcribed. For example in the picture below, a 'Recombinase 1' and 'Recombinase 2' would have to alter their respective 'Terminator' genes before the 'Output' gene will activate.

Most importantly, the changes triggered by signal compounds would be permanent. Lu's team found that the altered plasmids will be passed down through at least 90 cell generations, which could give a biologist valuable insight on when something may have happened in a cell's ancestry.Lu said that in theory, manufacturers could grow cell cultures that can produce drugs when triggered to, or grow cultures whose production can be halted with the introduction of signal compounds."


http://bit.ly/WKVOnx


original ref:

*Synthetic circuits integrating logic and memory in living cells* byPiro Siuti, John Yazbek & Timothy K Lu "Logic and memory are essential functions of circuits that generate complex, state-dependent responses. Here we describe a strategy for efficiently assembling synthetic genetic circuits that use recombinases to implement Boolean logic functions with stable DNA-encoded memory of events. Application of this strategy allowed us to create all 16 two-input Boolean logic functions in living Escherichia coli cells without requiring cascades comprising multiple logic gates. We demonstrate long-term maintenance of memory for at least 90 cell generations and the ability to interrogate the states of these synthetic devices with fluorescent reporters and PCR. Using this approach we created two-bit digital-to-analog converters, which should be useful in biotechnology applications for encoding multiple stable gene expression outputs using transient inputs of inducers. We envision that this integrated logic and memory system will enable the implementation of complex cellular state machines, behaviors and pathways for therapeutic, diagnostic and basic science applications." http://bit.ly/123ToU3
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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

Gerd Moe-Behrens's insight:

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
Gerd Moe-Behrens's insight:

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

comment to:

*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
Gerd Moe-Behrens's insight:

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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Startups Will Save America

Startups Will Save America | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
VIVEK WADHWA

The Wall Street Journal, The Accelerators

"Every few decades, America experiences a wave of pessimism.The population begins fearing economic stagnation and rising global competition, and starts leaning towards protectionism. Then, out of the blue, the country reinvents itself.

 Today, we fear China, earlier we feared Japan. But America is in the midst of its next great rebound. In this decade, it will reach new heights. That is because its scientists and engineers are developing an assortment of technologies that will solve the problems of health and security, bring knowledge and education to the masses, and create an abundance of energy, food and clean water. We can all observe the exponential advances in computing within the last decade — with our smartphones, social media, and health apps. The same advances are happening in many other fields, including synthetic biology, 3D printing, medicine and robotics. These are going to transform entire industries.
It isn’t the big research labs or governments who are creating these breakthroughs, it’s our entrepreneurs. And immigrants are leading the charge. During the recent technology boom, 52% of Silicon Valley’s startups were founded by people born abroad. Look at any of our research labs: Immigrants perform much of the cutting-edge research. Sadly, our flawed immigration policies are hurting innovation and may slow America’s rebound. Research by my team revealed that immigrant entrepreneurship in Silicon Valley has declined. Immigrants are getting frustrated with America’s immigration policies and leaving the country in droves. This is not only a loss for the U.S. — it’s a loss for the world. No other land is as fertile for innovation and entrepreneurship as the U.S.—yet. If we don’t fix our flawed policies, another country will surely surpass us. Our entrepreneurs will be competing with their former colleagues and classmates."

http://on.wsj.com/WCMEYv

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Becoming biohackers: Learning the game

Becoming biohackers: Learning the game | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
Hanno Charisius, Richard Friebe and Sascha Karberg

"More and more amateur biologists are carrying out genetic experiments in homes and garages worldwide. How easy is it to do? Three writers decided to find out.

When you have lunch courtesy of the FBI, you are offered chicken Caesar salad, hamburger or fish. Soft drinks are extra. Throughout our two-day visit we were happy to dine on FBI hamburgers and Caesar salad, but declined the seafood option. The atmosphere seemed fishy enough. We were in Walnut Creek, California, at the invitation of agent Nathaniel Head. He is a nice guy with a pleasant demeanour; there’s no furtive spy-like behaviour or obvious demonstration of power. He may be dressed in a smart khaki suit and striped tie (red, white and blue, of course), but he acts more like a professor. And thanks to a university background in microbiology, he is able to talk knowledgably about science. Head spared no effort in making us feel at ease, and the other agents present tried to do the same – all wide smiles and “glad-to-have-you-heres”. But despite this bonhomie, sitting in the windowless conference room in the basement of a nondescript hotel building in Walnut Creek still left us feeling uncomfortable. And it wasn’t just because there was a palpable Big Brother atmosphere in the room. Instead, we were acutely aware that we must have done something to bring us to the attention of Head; someone whose area of expertise is weapons of mass destruction....."



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Dan Rather Reports, "Cutting Edge" Promo for February 5, 2013

Gerd Moe-Behrens's insight:

*Dan Rather Reports*, "*Cutting Edge*" *Synthetic Biology* 

"Dan Rather Reports, "Cutting Edge" Promo from AXS TV. Like this? Watch the latest episode of AXS TV on Blip! http://blip.tv/hdnet-news-and-documen... ;

 Synthetic biology is at the forefront of modern science, as researchers reinvent cells by manipulating DNA to solve some of the most important problems facing the world."


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Organization of Synthetic Alphoid DNA Array in Human Artificial Chromosome (HAC) with a Conditional Centromere

Organization of Synthetic Alphoid DNA Array in Human Artificial Chromosome (HAC) with a Conditional Centromere | SynBioFromLeukipposInstitute | Scoop.it
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by
Kouprina N, Samoshkin A, Erliandri I, Nakano M, Lee HS, Fu H, Iida Y, Aladjem M, Oshimura M, Masumoto H, Earnshaw WC, Larionov V.

"Human artificial chromosomes (HACs) represent a novel promising episomal system for functional genomics, gene therapy and synthetic biology. HACs are engineered from natural and synthetic alphoid DNA arrays upon transfection into human cells. The use of HACs for gene expression studies requires the knowledge of their structural organization. However, none of de novo HACs constructed so far has been physically mapped in detail. Recently we constructed a synthetic alphoid(tetO)-HAC that was successfully used for expression of full-length genes to correct genetic deficiencies in human cells. The HAC can be easily eliminated from cell populations by inactivation of its conditional kinetochore. This unique feature provides a control for phenotypic changes attributed to expression of HAC-encoded genes. This work describes organization of a megabase-size synthetic alphoid DNA array in the alphoid(tetO)-HAC that has been formed from a ~50 kb synthetic alphoid(tetO)-construct. Our analysis showed that this array represents a 1.1 Mb continuous sequence assembled from multiple copies of input DNA, a significant part of which was rearranged before assembling. The tandem and inverted alphoid DNA repeats in the HAC range in size from 25 to 150 kb. In addition, we demonstrated that the structure and functional domains of the HAC remains unchanged after several rounds of its transfer into different host cells. The knowledge of the alphoid(tetO)-HAC structure provides a tool to control HAC integrity during different manipulations. Our results also shed light on a mechanism for de novo HAC formation in human cells."

http://bit.ly/VX5wV9

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Optogenetic tools for mammalian systems

Optogenetic tools for mammalian systems | SynBioFromLeukipposInstitute | Scoop.it
Light is fundamental to life on earth. Therefore, nature has evolved a multitude of photoreceptors that sense light across all kingdoms.
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by
Konrad Müller and Wilfried Weber

"Light is fundamental to life on earth. Therefore, nature has evolved a multitude of photoreceptors that sense light across all kingdoms. This natural resource provides synthetic biology with a vast pool of light-sensing components with distinct spectral properties that can be harnessed to engineer novel optogenetic tools. These devices enable control over gene expression, cell morphology and signaling pathways with superior spatiotemporal resolution and are maturing towards elaborate applications in basic research, in the production of biopharmaceuticals and in biomedicine. This article provides a summary of the recent advances in optogenetics that use light for the precise control of biological functions in mammalian cells."

http://rsc.li/VmRlGC

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RNA-Guided Human Genome Engineering via Cas9

RNA-Guided Human Genome Engineering via Cas9 | SynBioFromLeukipposInstitute | Scoop.it
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Prashant Mali, Luhan Yang, Kevin M. Esvelt, John Aach, Marc Guell, James E. DiCarlo, Julie E. Norville, George M. Church

"Bacteria and archaea have evolved adaptive immune defenses termed clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems that use short RNA to direct degradation of foreign nucleic acids. Here, we engineer the type II bacterial CRISPR system to function with custom guide RNA (gRNA) in human cells. For the endogenous AAVS1 locus, we obtained targeting rates of 10 to 25% in 293T cells, 13 to 8% in K562 cells, and 2 to 4% in induced pluripotent stem cells. We show this process relies on CRISPR components, is sequence-specific, and upon simultaneous introduction of multiple gRNAs, can effect multiplex editing of target loci. We also compute a genome-wide resource of ~190k unique gRNAs targeting ~40.5% of human exons. Our results establish an RNA-guided editing tool for facile, robust, and multiplexable human genome engineering."

http://bit.ly/15hHvcZ

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New Tool for Genome Surgery

New Tool for Genome Surgery | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by
John van der Oost

"Gene therapy is the holy grail of human medicine. Many diseases are caused by a defective gene, sometimes with a mutation as subtle as a single-nucleotide variation. Before restoration of such a mutation in a patient's genome can take place, the target nucleotide sequence has to be cleaved at a single position, out of 3 billion possibilities. This degree of precise surgery requires an enzyme with highly selective target recognition. Successful editing of eukaryotic genomes has been accomplished with DNA nucleases designed to bear a unique site that binds to a specific DNA sequence. A major drawback of these protein-guided systems to "engineer" genomes, however, is that each new target sequence requires laboriously adjusting the specificity of the nuclease's DNA binding site. On pages 819 and 823 of this issue, Cong et al. (1) and Mali et al. (2) describe efficient genome editing in human cells based on an RNA-guided system."
http://bit.ly/XSpKf0

Referring to:
*Multiplex Genome Engineering Using CRISPR/Cas Systems*
by
Le Cong et al.
http://bit.ly/VVv3yb

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