SynBioFromLeukipposInstitute

by

Mengjin Liu,  Bruno Bienfait,  Oliver Sacher,  Johann Gasteiger,  Roland J. Siezen,  Arjen Nauta, 

 Jan M. W. Geurts 

"The incompleteness of genome-scale metabolic models is a major bottleneck for systems biology approaches, which are based on large numbers of metabolites as identified and quantified by metabolomics. Many of the revealed secondary metabolites and/or their derivatives, such as flavor compounds, are non-essential in metabolism, and many of their synthesis pathways are unknown. In this study, we describe a novel approach, Reverse Pathway Engineering (RPE), which combines chemoinformatics and bioinformatics analyses, to predict the "missing links" between compounds of interest and their possible metabolic precursors by providing plausible chemical and/or enzymatic reactions. We demonstrate the added-value of the approach by using flavor-forming pathways in lactic acid bacteria (LAB) as an example. Established metabolic routes leading to the formation of flavor compounds from leucine were successfully replicated. Novel reactions involved in flavor formation, i.e. the conversion of alpha-hydroxy-isocaproate to 3-methylbutanoic acid and the synthesis of dimethyl sulfide, as well as the involved enzymes were successfully predicted. These new insights into the flavor-formation mechanisms in LAB can have a significant impact on improving the control of aroma formation in fermented food products. Since the input reaction databases and compounds are highly flexible, the RPE approach can be easily extended to a broad spectrum of applications, amongst others health/disease biomarker discovery as well as synthetic biology." 

http://bit.ly/LaT2VD

http://huff.to/1gMpXds

by
Chenli Liu, Xiongfei Fu, Jian-Dong Huang

"The principles and molecular mechanisms underlying biological pattern formation are difficult to elucidate in most cases due to the overwhelming physiologic complexity associated with the natural context. The understanding of a particular mechanism, not to speak of underlying universal principles, is difficult due to the diversity and uncertainty of the biological systems. Although current genetic and biochemical approaches have greatly advanced our understanding of pattern formation, the progress mainly relies on experimental phenotypes obtained from time-consuming studies of gain or loss of function mutants. It is prevailingly considered that synthetic biology will come to the application age, but more importantly synthetic biology can be used to understand the life. Using periodic stripe pattern formation as a paradigm, we discuss how to apply synthetic biology in understanding biological pattern formation and hereafter foster the applications like tissue engineering."


 http://bit.ly/1ksmuXd

By Matt Davenport

"Stanford scientists genetically engineer versions of myosin proteins that transport biological materials in cells to illuminate design features that keep these protein motors on track.

Inside our cells, proteins known as myosins can act as a delivery service for biological materials. To better understand how molecular motors move, Stanford bioengineers have built experimental versions of the proteins, changing the way these transporters get around. Led by Zev Bryant, an assistant professor of bioengineering at Stanford, a team of researchers has genetically engineered “mutant” myosins with new features such as gearshifts and improved traction. The group’s most recent findings are published in the January issue of Nature Nanotechnology, where they are highlighted alongside other studies of molecular motors. “You look at biology, and you see motors that have diverse mechanical properties, and you want to understand how these arise,” Bryant said. “You test your understanding by trying to build something new.” Molecular motors are a class of proteins that make up the moving machinery of cells. Myosins are one family of molecular motors. Some of them can shuttle biomolecules from one region of the cell to another. These myosins move along microscopic filaments made of the protein known as actin. These actin filaments are one component of the cytoskeleton, or internal support structure of the cell. Bryant wanted to test his understanding of how evolution has designed these myosin proteins to shuttle cellular freight. Funded by an NIH “New Innovator” Award, members of the group launched a series of experiments in 2008 that steered their myosin research in a new direction. They began engineering myosins with extra parts to give natural myosins new capabilities. Natural myosins, for example, see actin filaments as one-way tracks. To better understand this one-directional motion, Bryant challenged his group to design mutant myosins that could move forward and backward on command. The researchers engineered myosin motors with extra components that behaved like a molecular gearshift. In a 2012 Nature Nanotechnology report, the researchers showed that they could shift their mutant myosin motion between forward and reverse. However, these two-way myosins had trouble hanging onto their actin tracks. “When we engineer motors to have new capabilities, we often sacrifice some capabilities that they already had,” Bryant said. So the group focused on creating motors that excelled at hanging on....."

http://stanford.io/19Yz2yP

by
Tom Ashbrook

"In the spring of 2010, Craig Venter – the “richest and most powerful man in biotechnology,” he’s been called – announced the creation of a new life form.  Synthetic life.  Genetically coded on a computer, and popped to life.  Specifications dropped in by a human hand.  Self-replicating and ready to go.  It was a bombshell in biology circles.  The rest of the world is still taking it onboard.  Now Venter’s talking about it as a challenge to our understanding of life itself.  A boon, he hopes.  And maybe a teleporter, too.  Up next On Point:  Craig Venter on the advance of synthetic life."


 http://bit.ly/1iNwXL9

by
JAMES H BEVAN

"Synthetic biology is unlocking the extraordinary potential of genetic code, inventing powerful new living devices and reinventing existing biological processes. As genomes are mapped, combinations of genes that perform useful functions are continually pinpointed, borrowed, altered and recombined to develop new variants of life with endless possibilities.

 As our knowledge of DNA grows, advances in the field are made on a daily basis, allowing scientists to devise innovative new bacteria that can seemingly do anything, from cleaning up pollution, diagnosing diseases, delivering vaccines or sustainably producing scarce chemicals. At the cutting edge of this innovation are synthetic biology companies combining bioscience, chemistry, information technology and engineering to tailor-make microorganisms that perform useful functions. Each step of the process, from mapping specific genes to designing then coding unique bacteria, through to breeding and testing is developing its own industry as the staggering potential of genetic code is realised. Synthace is the first company in the UK to specialise solely in the synthesis of new biological production systems, overseeing design all the way through to application. A spin-off from UCL, Synthace uses the university’s biochemical engineering facilities to test its innovative biological inventions that have applications for a range of industries. The UK’s innovation agency has taken notice. In March 2013, the Technology Strategy Board awarded Synthace a £500,000 grant in collaboration with UCL and the University of Manchester for the "Rapid Engineering of Cellular Factories". Using the suite of novel technologies at the firm’s disposal, the project’s ambitious aim is to tune cells that can convert abundant feedstocks such as vegetable oil into high value chemicals such as pigments, fragrances and pharmaceutical ingredients.  “The project will demonstrate a new way of engineering biology, with timescales in months rather than years,” explained Synthace CTO Sean Ward, “which will impact sectors across the UK and global economies”. Cellular factories These new cellular factories not only promise to cut the cost and time normally associated with chemical production, but also waste, risk and energy use. Announcing the award, Universities and Science Minister David Willetts predicted that synthetic biology will play “an increasingly important part in the global economy over the coming years”, observing that the UK “is among the first economies in the world to invest in this exciting area of technology”. Though the commercial applications of synthetic biology are yet to be fully realised, students across the world are continually pushing the boundaries of biochemical science into the realm of science fiction..."

http://ind.pn/1dtA2MJ

We need net neutrality for science.

Thus sad news:

*Net neutrality rules struck down by court. Is open Internet dead?*

http://bit.ly/1iX0YWh

It might be the time to organize large scale alternatives in a decentralized peer to peer manner....

*Can synthetic biology revolutionize the field of stem cell therapy?*

by 
Anonymous

"When it comes to 21st-century medicine, it doesn’t get any better than using cells to cure or repair what ails you.

 Stem cell therapies hold great promise for the repair and regeneration of diseased tissues because of their ability to sense and integrate complex environmental signals, to migrate to diseased tissues and to execute complex responses. Stem cells have been used successfully in the lab to repair damaged heart muscle or restore movement to paralyzed limbs. However, this complexity also presents significant safety concerns—such as tumor formation or inappropriate functionality—which have discouraged the widespread use of stem cells for the treatment of major diseases such as diabetes or Alzheimer’s. One way to accelerate the safe development of cell therapies is by using synthetic biology to engineer external control of multiple complex cellular functions. Indeed, proof-of-principle studies have already demonstrated that synthetic biology techniques can control cell proliferation and cell death, redirect cell migration, and control the expression of selected proteins and direct intracellular communication..."

 http://bit.ly/1eAo69S

by
Mohammad R. Seyedsayamdost and Jon Clardy 

"While the phrasing of this tripartite classification was not intended to describe the current state of natural products research, it could have been, as it provides an apt description of the field today. The organic molecules lumped under the term natural products elude an easy definition. They are a structurally diverse collection of molecules produced by organisms in an idiosyncratic fashion, and their biological activities reflect the diversity of their producers and structures. Inclusion in or exclusion from the natural product family reflects the elasticity of classification. Consider three molecules that are closely related structurally and biosynthetically: tryptophan, serotonin, and psilocin (Figure 1a). Tryptophan’s universal distribution as a proteinogenic amino acid excludes it from being a natural product. Serotonin’s widespread distribution and well-understood biological activities result in its classification as a hormone or neurotransmitter, while psilocin, a hallucinogenic relative produced by only a few New World mushrooms, is a natural product. All natural products have one feature in common, biosyntheses by a genetically encoded pathway, and the possibilities for re-engineering these pathways connects natural products to synthetic biology."

 http://bit.ly/1augc37

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..."

 http://bit.ly/19Ywxwn