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3quarksdaily: Synthetic Biology: Engineering Life To Examine It

3quarksdaily: Synthetic Biology: Engineering Life To Examine It | Bioinformatics Training | Scoop.it

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Socrates Logos's curator insight, January 7, 5:33 AM

by
Jalees Rehman

*Two scientific papers that were published in the journal Nature in the year 2000 marked the beginning of engineering biological circuits in cells. The paper "Construction of a genetic toggle switch in Escherichia coli" by Timothy Gardner, Charles Cantor and James Collins created a genetic toggle switch by simultaneously introducing an artificial DNA plasmid into a bacterial cell. This DNA plasmid contained two promoters (DNA sequences which regulate the expression of genes) and two repressors (genes that encode for proteins which suppress the expression of genes) as well as a gene encoding for green fluorescent protein that served as a read-out for the system. The repressors used were sensitive to either selected chemicals or temperature. In one of the experiments, the system was turned ON by adding the chemical IPTG (a modified sugar) and nearly all the cells became green fluorescent within five to six hours. Upon raising the temperature to activate the temperature-sensitive repressor, the cells began losing their green fluorescence within an hour and returned to the OFF state. Many labs had used chemical or temperature switches to turn gene expression on in the past, but this paper was the first to assemble multiple genes together and construct a switch which allowed switching cells back and forth between stable ON and OFF states.

 Dna-163466_640 The same issue of Nature contained a second land-mark paper which also described the engineering of gene circuits. The researchers Michael Elowitz and Stanislas Leibler describe the generation of an engineered gene oscillator in their article "A synthetic oscillatory network of transcriptional regulators". By introducing three repressor genes which constituted a negative feedback loop and a green fluorescent protein as a marker of the oscillation, the researchers created a molecular clock in bacteria with an oscillation period of roughly 150 minutes. The genes and proteins encoded by the genes were not part of any natural biological clock and none of them would have oscillated if they had been introduced into the bacteria on their own. The beauty of the design lay in the combination of three serially repressing genes and the periodicity of this engineered clock reflected the half-life of the protein encoded by each gene as well as the time it took for the protein to act on the subsequent member of the gene loop.  Both papers described the introduction of plasmids encoding for multiple genes into bacteria but this itself was not novel. In fact, this has been a routine practice since the 1970s for many molecular biology laboratories. The panache of the work lay in the construction of functional biological modules consisting of multiple genes which interacted with each other in a controlled and predictable manner. Since the publication of these two articles, hundreds of scientific papers have been published which describe even more intricate engineered gene circuits. These newer studies take advantage of the large number of molecular tools that have become available to query the genome as well as newer DNA plasmids which encode for novel biosensors and regulators. Synthetic biology is an area of science devoted to engineering novel biological circuits, devices, systems, genomes or even whole organisms. This rather broad description of what "synthetic biology" encompasses reflects the multidisciplinary nature of this field which integrates ideas derived from biology, engineering, chemistry and mathematical modeling as well as a vast arsenal of experimental tools developed in each of these disciplines. Specific examples of "synthetic biology" include the engineering of microbial organisms that are able to mass produce fuels or other valuable raw materials, synthesizing large chunks of DNA to replace whole chromosomes or even the complete genome in certain cells, assembling synthetic cells or introducing groups of genes into cells so that these genes can form functional circuits by interacting with each other. Synthesis in the context of synthetic biology can signify the engineering of artificial genes or biological systems that do not exist in nature (i.e. synthetic = artificial or unnatural), but synthesis can also stand for integration and composition, a meaning which is closer to the Greek origin of the word.  It is this latter aspect of synthetic biology which makes it an attractive area for basic scientists who are trying to understand the complexity of biological organisms. Instead of the traditional molecular biology focus on studying just one single gene and its function, synthetic biology is engineering biological composites that consist of multiple genes and regulatory elements of each gene. This enables scientists to interrogate the interactions of these genes, their regulatory elements and the proteins encoded by the genes with each other. Synthesis serves as a path to analysis. One goal of synthetic biologists is to create complex circuits in cells to facilitate biocomputing, building biological computers that are as powerful or even more powerful that traditional computers. While such gene circuits and cells that have been engineered have some degree of memory and computing power, they are no match for the comparatively gigantic computing power of even small digital computers. Nevertheless, we have to keep in mind that the field is very young and advances are progressing at a rapid pace. One of the major recent advances in synthetic biology occurred in 2013 when an MIT research team led by Rahul Sarpeshkar and Timothy Lu at MIT created analog computing circuits in cells. Most synthetic biology groups that engineer gene circuits in cells to create biological computers have taken their cues from contemporary computer technology. Nearly all of the computers we use are digital computers, which process data using discrete values such as 0's and 1's. Analog data processing on the other hand uses a continuous range of values instead of 0's and 1's. Digital computers have supplanted analog computing in nearly all areas of life because they are easy to program, highly efficient and process analog signals by converting them into digital data. Nature, on the other hand, processes data and information using both analog and digital approaches. Some biological states are indeed discrete, such as heart cells which are electrically depolarized and then repolarized in periodical intervals in order to keep the heart beating. Such discrete states of cells (polarized / depolarized) can be modeled using the ON and OFF states in the biological circuit described earlier. However, many biological processes, such as inflammation, occur on a continuous scale. Cells do not just exist in uninflamed and inflamed states; instead there is a continuum of inflammation from minimal inflammatory activation of cells to massive inflammation. Environmental signals that are critical for cell behavior such as temperature, tension or shear stress occur on a continuous scale and there is little evidence to indicate that cells convert these analog signals into digital data. Most of the attempts to create synthetic gene circuits and study information processing in cells have been based on a digital computing paradigm. Sarpeshkar and Lu instead wondered whether one could construct analog computation circuits and take advantage of the analog information processing systems that may be intrinsic to cells. The researchers created an analog synthetic gene circuit using only three proteins that regulate gene expression and the fluorescent protein mCherry as a read-out. This synthetic circuit was able to perform additions or ratiometric calculations in which the cumulative fluorescence of the mCherry was either the sum or the ratio of selected chemical input concentrations. Constructing a digital circuit with similar computational power would have required a much larger number of components.  The design of analog gene circuits represents a major turning point in synthetic biology and will likely spark a wave of new research which combines analog and digital computing when trying to engineer biological computers. In our day-to-day lives, analog computers have become more-or-less obsolete. However, the recent call for unconventional computing research by the US Defense Advanced Research Projects Agency (DARPA) is seen by some as one indicator of a possible paradigm shift towards re-examining the value of analog computing. If other synthetic biology groups can replicate the work of Sarpeshkar and Lu and construct even more powerful analog or analog-digital hybrid circuits, then the renaissance of analog computing could be driven by biology.  It is difficult to make any predictions regarding the construction of biological computing machines which rival or surpass the computing power of contemporary digital computers. What we can say is that synthetic biology is becoming one of the most exciting areas of research that will provide amazing insights into the complexity of biological systems and may provide a path to revolutionize biotechnology..."


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Sandrine Palcy's curator insight, January 9, 5:11 AM

From computing biology to biology for computing...!

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Bioinformatics, blended with education and health sciences subjects
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BioCoder

BioCoder | Bioinformatics Training | Scoop.it
BioCoder is a quarterly newsletter for DIYbio, synthetic bio, and anything related.

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Socrates Logos's curator insight, July 17, 6:51 PM

*A great new edition of BioCoder*

free PDF, epub, mobi

http://oreil.ly/WfVCzh

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Careers in Bioinformatics and Precision Medicine - Career Development Week

Visit: http://www.uctv.tv/) Precision medicine integrates molecular and clinical research with patient data and outcomes, aiming to place the patient at the...
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Must Read Report: The Internet’s Latest Disruption – Knowledge.

Must Read Report: The Internet’s Latest Disruption – Knowledge. | Bioinformatics Training | Scoop.it
Know or die: risk and opportunity of Knowledge 2.0
“And the web stormed the enterprise and disrupted roles, tasks and jobs: it cast speed, openness, flexibility and efficiency throughout, sparing no business processes: manufacturing, logistic, accounting, customer relation management, lead generation…”
The digital mutation is also profoundly disrupting how knowledge is acquired, organized and shared. Knowledge is an intangible, yet strategic asset of any enterprise. With businesses becoming more virtual and dematerialized, its value is patently and rapidly growing. Continue reading →
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Google Will Finance Carnegie Mellon’s MOOC Research

Google Will Finance Carnegie Mellon’s MOOC Research | Bioinformatics Training | Scoop.it
Carnegie Mellon University’s receiving a grant to study MOOCs is no surprise. But the source’s identity is bound to raise eyebrows.
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Bioinformatics course15 how to screen vector contamination using vecscreen

This bioinformatics tutorial under bioinformatics lecture series explains how to screen gene sequence for vector sequence contamination using vecscreen software online. For more information,...
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Bioinformatics practical 14 how to calculate % GC content and molecular weight of a gene

This bioinformatics tutorial under bioinformatics lecture series explains how to calculate % GC content and molecular weight of a gene For more information, log on to- http://shomusbiology.weebly....
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Bioinformatics course 20 how to know the physicochemical properties of a protein

This bioinformatics course under bioinformatics lecture series explains the process of knowing physicochemical properties of a protein sequence. For more information, log on to- http://shomusbiolog...
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Bioinformatics practical 24 how to use PROSITESCAN

This bioinformatics tutorial explains how to use PROSITESCAN tool to find known protein domains in protein database. For more information, log on to- http://shomusbiology.weebly.com/ Download...
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Bioinformatics practical 23 motif scan tool to identify known domains in protein sequence

This bioinformatics tutorial explains use of motif scan tool to identify known domains in protein sequence. For more information, log on to- http://shomusbiology.weebly.com/ Download the study...
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Should You Build a Data Center Today? 2 Universities, 2 Answers

Should You Build a Data Center Today? 2 Universities, 2 Answers | Bioinformatics Training | Scoop.it
When it comes to building campuses from scratch in the information age, few institutions have a track record like New York University’s. Under its current president, John E. Sexton, NYU has opened campuses in Abu Dhabi and Shanghai.
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Biocaml: The OCaml Bioinformatics Library

Ashish Agarwal http://video.open-bio.org/video/14/biocaml-the-ocaml-bioinformatics-library.
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The Promise of Plasma Proteomics in the Clinical Laboratory: Fact and Fiction

The striking shortfall in new protein diagnostics emerging from proteomics research reflects a lack of critical biomarker verification capacity, in combination with other factors underlying...
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Keystone Symposia: Precision Genome Engineering and Synthetic Biology 2015 | January 11th | clocate - Conferences and Exhibitions

Keystone Symposia: Precision Genome Engineering and Synthetic Biology 2015 | January 11th | clocate - Conferences and Exhibitions | Bioinformatics Training | Scoop.it
Keystone Symposia: Precision Genome Engineering and Synthetic Biology 2015 will be held in Big sky, MT, United States on January 11th.

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ISB Researchers Help Identify Four New Subtypes of Gastric Cancer That May Lead to New Targeted Treatments

ISB Researchers Help Identify Four New Subtypes of Gastric Cancer That May Lead to New Targeted Treatments | Bioinformatics Training | Scoop.it
3 Bullets:
Gastric cancer has a high mortality rate, but current classification systems haven’t been effective in helping to identify subtypes relevant for treatment of the disease.
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Jon Spaihts: Hollywood’s go-to science fiction screenwriter on the importance of science in filmmaking

Jon Spaihts: Hollywood’s go-to science fiction screenwriter on the importance of science in filmmaking | Bioinformatics Training | Scoop.it
Hollywood’s go-to science fiction writer.

Jon Spaihts is the screenwriter of The Darkest Hour, Ridley Scott’s Prometheus and the upcoming Passengers and The Mummy.
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L’université de demain : des cours gratuits, à toute heure...

L’université de demain : des cours gratuits, à toute heure... | Bioinformatics Training | Scoop.it
Des cours dispensés la nuit ou sans horaire fixe, des bibliothèques virtuelles, des ressources pédagogiques et l’accès au matériel gratuits…...

 


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juandoming's curator insight, July 19, 12:43 PM

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Online Upstart’s Goal: MOOC Lectures That Go Viral

Online Upstart’s Goal: MOOC Lectures That Go Viral | Bioinformatics Training | Scoop.it
Donald J. Boudreaux’s five-minute video lecture on the evolution of human prosperity—complete with slick animation, studio lightning, and killer graphics—looks seamless. Making it, he says, was anything but.
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Bioinformatics practical 18 how to predict translation product of a gene sequence?

This bioinformatics tutorial under bioinformatics lecture series explains how to predict the translated product of a gene using expasy tools. For more information, log on to- http://shomusbiology.w...
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Bioinformatics course 16 primer design

This bioinformatics tutorial explains how to design primer using NCBI primer Designing tool. For more information, log on to- http://shomusbiology.weebly.com/ Download the study materials here-...
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Bioinformatics practical 22 how to search for known domains in protein sequence

This bioinformatics tutorial under bioinformatics lecture series explains how to search known protein domains in a protein sequence. For more information, log on to- http://shomusbiology.weebly.com...
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Bioinformatics practical 21 how to find transmembrane region in protein sequence

This bioinformatics tutorial explains how to find a trans membrane domain in protein sequence using sliding window approach. For more information, log on to- http://shomusbiology.weebly.com/...
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Bioinformatics practical 22 how to search for known domains in protein sequence

This bioinformatics tutorial under bioinformatics lecture series explains how to search known protein domains in a protein sequence. For more information, log on to- http://shomusbiology.weebly.com...
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11 University and Library Groups Release Net-Neutrality Principles

11 University and Library Groups Release Net-Neutrality Principles | Bioinformatics Training | Scoop.it
The nation’s colleges and libraries have a message for the Federal Communications Commission: Don’t mess with net neutrality.
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A History of Bioinformatics (in the Year 2039)

C. Titus Brown http://video.open-bio.org/video/1/a-history-of-bioinformatics-in-the-year-2039.
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BioCoder: Issue 4

BioCoder: Issue 4 | Bioinformatics Training | Scoop.it

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Socrates Logos's curator insight, July 15, 7:24 PM

Our work in the latest issue of BioCoder:

*Leukippos: A Synthetic Biology Lab in the Cloud*

by
Pablo Cárdenas, Maaruthy Yelleswarapu, Sayane Shome, Jitendra Kumar Gupta, Eugenio Maria Battaglia, Pedro Fernandes, Alioune Ngom, and Gerd Moe-Behrens

"As we move deeper into the digital age, the social praxis of science undergoes fundamental changes, driven by new tools provided by information and communication technologies. Specifically, social networks and computing resources such as online cloud-based infrastructures and applications provide the necessary context for unprecedented innovations in modern science. These tools are leading to a planetary-scale connectivity among researchers and enable the organization of in silico research activities entirely through the cloud.

Research collaboration and management via the cloud will result in a drastic expansion of our problem-solving capacity, since groups of people with different backgrounds and expertise that openly gather around common interests are more likely to succeed at solving complex problems. Another advantage is that collaboration between individuals becomes possible regardless of their geographic location and background.
Here we present a novel, open-web application called Leukippos, which aims to apply these information and communication technologies to in silico synthetic biology projects. We describe both the underlying technology and organizational structure necessary for the platform’s operation. The synthetic biology software search engine, SynBioAppSelector, and the game, SynBrick, are examples of projects being developed on this platform."



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