SynBioFromLeukipposInstitute

by
Oliver Purcell, Bonny Jain, Jonathan R. Karr, Markus W. Covert, and Timothy K. Lu

"Despite rapid advances over the last decade, synthetic biology lacks the predictive tools needed to enable rational design. Unlike established engineering disciplines, the engineering of synthetic gene circuits still relies heavily on experimental trial-and-error, a time-consuming and inefficient process that slows down the biological design cycle. This reliance on experimental tuning is because current modeling approaches are unable to make reliable predictions about the in vivo behavior of synthetic circuits. A major reason for this lack of predictability is that current models view circuits in isolation, ignoring the vast number of complex cellular processes that impinge on the dynamics of the synthetic circuit and vice versa. To address this problem, we present a modeling approach for the design of synthetic circuits in the context of cellular networks. Using the recently published whole-cell model of Mycoplasma genitalium, we examined the effect of adding genes into the host genome. We also investigated how codon usage correlates with gene expression and find agreement with existing experimental results. Finally, we successfully implemented a synthetic Goodwin oscillator in the whole-cell model. We provide an updated software framework for the whole-cell model that lays the foundation for the integration of whole- cell models with synthetic gene circuit models. This software framework is made freely available to the community to enable future extensions. We envision that this approach will be critical to transforming the field of synthetic biology into a rational and predictive engineering discipline...."



 http://stanford.io/14fdqc6

*Biology: The big challenges of big data* 

by
Vivien Marx

"Biologists are joining the big-data club. With the advent of high-throughput genomics, life scientists are starting to grapple with massive data sets, encountering challenges with handling, processing and moving information that were once the domain of astronomers and high-energy physicists1.

 With every passing year, they turn more often to big data to probe everything from the regulation of genes and the evolution of genomes to why coastal algae bloom, what microbes dwell where in human body cavities and how the genetic make-up of different cancers influences how cancer patients fare2. The European Bioinformatics Institute (EBI) in Hinxton, UK, part of the European Molecular Biology Laboratory and one of the world's largest biology-data repositories, currently stores 20 petabytes (1 petabyte is 1015 bytes) of data and back-ups about genes, proteins and small molecules. Genomic data account for 2 petabytes of that, a number that more than doubles every year3 (see 'Data explosion'). This data pile is just one-tenth the size of the data store at CERN, Europe's particle-physics laboratory near Geneva, Switzerland. Every year, particle-collision events in CERN's Large Hadron Collider generate around 15 petabytes of data — the equivalent of about 4 million high-definition feature-length films. But the EBI and institutes like it face similar data-wrangling challenges to those at CERN, says Ewan Birney, associate director of the EBI. He and his colleagues now regularly meet with organizations such as CERN and the European Space Agency (ESA) in Paris to swap lessons about data storage, analysis and sharing.  SOURCE: EMBL–EBIDownload PDF All labs need to manipulate data to yield research answers. As prices drop for high-throughput instruments such as automated genome sequencers, small biology labs can become big-data generators. And even labs without such instruments can become big-data users by accessing terabytes (1012 bytes) of data from public repositories at the EBI or the US National Center for Biotechnology Information in Bethesda, Maryland. Each day last year, the EBI received about 9 million online requests to query its data, a 60% increase over 2011...."

http://bit.ly/16o9ozW

by
+David Bikard  Wenyan Jiang, Poulami Samai, Ann Hochschild, Feng Zhang and Luciano A. Marraffini

"The ability to artificially control transcription is essential both to the study of gene function and to the construction of synthetic gene networks with desired properties. Cas9 is an RNA-guided double-stranded DNA nuclease that participates in the CRISPR-Cas immune defense against prokaryotic viruses. We describe the use of a Cas9 nuclease mutant that retains DNA-binding activity and can be engineered as a programmable transcription repressor by preventing the binding of the RNA polymerase (RNAP) to promoter sequences or as a transcription terminator by blocking the running RNAP. In addition, a fusion between the omega subunit of the RNAP and a Cas9 nuclease mutant directed to bind upstream promoter regions can achieve programmable transcription activation. The simple and efficient modulation of gene expression achieved by this technology is a useful asset for the study of gene networks and for the development of synthetic biology and biotechnological applications.>>"


http://bit.ly/16k79xv

*Supreme Court Decision Opens the Doors to A Boom in Synthetic Biology* 

by
Morgan Clendaniel

"Today’s Supreme Court ruling on the patenting of human genes was a boost to the field of synthetic biology. While human genes cannot be directly patented, the Court found, so-called complementary DNA can. This is DNA that is synthesized from the rNA in a genetic template and then cloned. The Court found that while naturally occurring DNA is not a human creation, "the lab technician unquestionably creates something new when cDNA is made. "

Synthetic biology relies on this synthesized cDNA. Synthetic biology has been in the news lately for many reasons. Last Friday a unique Kickstarter campaign closed with almost $500,000 in donations (well over a $65,000 goal). As a result, three young DIY bio enthusiasts will distribute to almost 6,000 backers, who kicked in at least $40 each, packages of synthetically genetically engineered seeds that supposedly will allow each of them to grow bioluminescent house plants--Arabidopsis and eventually roses--at home. Synthetic biology is an emerging and controversial scientific field that uses gene-writing software to compile DNA sequences, in this case, taken and modified from a firefly, that are then printed onto a blotter. The Glowing Plants project will use a "Gene Gun" to "fire" particles of gold coated in DNA into living cells. The use of the gun does an end run around USDA regulations that govern the use of viruses or other pathogens to modify DNA. The project started at Singularity University. It’s designed as a public demonstration of the power of DIY Biology. And herein lies the problem for some critics. The potential applications of synthetic biology are to create immensely useful, lifesaving things, like a cure for Alzheimer’s disease, or a rice crop that needs as little water as a cactus, or an algae or other single-celled species that can produce near-perfect petroleum analogues from the sun or from toxic chemicals. These glowing plants don’t do any of that, and scientists and environmentalists question if the wow factor is really worth the risk. Though the project is technically legal, its sheer hubris has kickstarted some serious from scientists and environmental groups that object to the release of these seeds to the public, with the chance that the DNA will get into the natural gene pool with unknown consequences. An anti-synthetic bio group called ETC has started a fundraising drive of their own, dubbed a "Kickstopper." "To date all [experts] have agreed that no synthetic organisms should yet be released into the environment without 'precaution,' 'prudent vigilance,' regulation, monitoring and other sober and sensible safeguards. Yet now the US government appears ready to avert its eyes," they write on their website. And a on Avaaz.org has over 13,000 signatures. Other scientists object that it’s unlikely that the small plant will actually be able to process enough energy to visibly glow, even slightly or for a few seconds at a time. The journal Nature notes that the Glowing Plants project is among other genetically modified, glow in the dark creature to be available to the public soon. A company called BioGlow in St. Louis also intends to sell glowing houseplants. Commercially available synthetically engineered animals, to say nothing of human cDNA, are still far away, but if they appear, they’ll be protected by intellectual property law."

http://bit.ly/11cFDBA

by
JEFFREY MARLOW

"For millennia, people have gone out of their way to change the biological world around them. We’ve killed threatening species, domesticated others, and manipulated the habitats of still others to make food production and basic survival an easier undertaking. So the notion that our tinkering with nature is a fundamental departure from a past Eden in which we were “a part of nature” is a false dichotomy: every action we take – and some have been more intentional than others – contributes to a changing world.

 The potential magnitude of our intervention, however, is greater today than ever before. Before the advent of molecular biology, the complexity of living systems kept the underlying mechanisms of our tinkering obscure. We may engage in selective breeding (a crude form of biological engineering) to produce a more productive crop or a cuter dog, but our metric of selection – size of an ear of corn, or furriness – is the end result of millions of intricate biological interactions. Following the great reductionist tradition of experimental science, we’ve traced biological function to the genetic level and are now looking for codified ways of enacting discrete interventions in predictable ways. This is synthetic biology: a young field promising great things.  Kevin Munnelly is the President and CEO of Gen9, a company founded by some of the biggest names in synthetic biology research to commercialize a better way of synthesizing DNA. In a recent article published in the journal ACS Synthetic Biology, Munnelly outlines the transformative potential of the field and identifies a key obstacle standing in its way: standardization. As experimental techniques have advanced, individual researchers have jumped right in, designing new genes or regulatory elements, seeing how they affect a microbe, and publishing the results. Another scientist may have accomplished the same feat in a different way, leading future investigators unclear on which method is most desirable. If there were a trusted repository of DNA sequences vetted to produce certain results to spec, it would save a lot of time and minimize the number of variables in a given experiment. Standardization of parts is not a particularly glamorous field of work, but, leading synthetic biologists, agree, it’s essential. Imagine trying to construct a Boeing Dreamliner from a heap of metal and wires. Standard parts get everyone on the same 8.5”x11” page. Fortunately, the global community of synthetic biology coppersmiths is already building a stockroom. The Registry for Standard Biology Parts is up to more than 7000 components. “These are all annotated and confirmed gene sequences,” explains Munnelly, “vetted through peer review publications or public companies that provide validation.” Things like gene promoters, protein coding domains, termination sequences, plasmids, vector sequences, or genes for specific functions...."

http://bit.ly/18Dfpgl

By Christina Agapakis 

"What is the origin of life on Earth? What is the future of life in the age of synthetic biology? These are two of the biggest questions of contemporary biology, and the questions that drive Adam Rutherford’s new book, Creation: How Science is Reinventing Life Itself, a compelling and accessible two-part look through the history and future of living cells. Through chapters that span the early history of microscopy to recent debates on the regulation of biotechnology and genomics, Rutherford tells the complicated story of the science of life as it might have been and as it might be. These two difficult questions, of origins and offspring, have been tightly linked in the life sciences for over a century. In the work of engineer-biologists like Jacques Loeb–who at the beginning of the 20th century sought to create “artificial life” through manipulation of sea urchin eggs–engineering was a tool for experimentation to better understand biology. For Loeb, engineering could be used to examine the validity of biological theory: “the proof of the explicability of any single life phenomenon is furnished as soon at it is successfully controlled unequivocally through physical or chemical means or is repeated in all details with nonliving materials.” Echoes of this sentiment are found everywhere in synthetic biology today, where Richard Feynman’s much more quotable remark is frequently invoked: “What I cannot create, I do not understand.”..."

http://bit.ly/12GWKhP

DIYBio Hangout: Wed 12th June 11am PDT http://bit.ly/12DXswc

By Christina Agapakis 

*Bacteria are single celled organisms that can do amazing things in multicellular groups, with complex coordinated behaviors emerging from the interaction of genetic networks, chemical environments, and the physics of cell growth. Last year I wrote about the work of Tim Rudge and Fernan Federici and their incredible images of bacterial growth patterns. Their paper, with colleagues from the Haseloff Lab at the University of Cambridge, was recently published in ACS Synthetic Biology, showing how complex fractal patterns in colonies of E. coli emerge simply from the physical interactions of rod shaped cells.
In this experiment, E. coli cells are labelled with two colors of fluorescent protein (they are otherwise genetically identical) and seeded at low density onto a surface. As they grow and divide, the rod shaped cells begin to bump into each other, creating jagged boundaries between the two fluorescent populations. These jagged lines are fractal, self-similar at many scales. Using their CellModeller program, the team found that they could accurately model this fractal behavior by including only physical parameters like viscous drag, cell shape, and growth rate, rather than biological properties like cell-cell communication or chemotaxis. Indeed, when they used E. coli mutants that were spherical instead of rod-shaped, the fractal pattern disappeared..."

http://bit.ly/ZFKtWN

Printing innovations provide tenfold improvement in organic electronics http://bit.ly/12d2PRx

by
Daniel E. Agnew, Brian F. Pfleger

"Constructing polycistronic operons is an advantageous strategy for coordinating the expression of ­multiple genes in a prokaryotic host. Unfortunately, a basic construct consisting of an inducible promoter and genes cloned in series does not generally lead to optimal results. Here, a combinatorial approach for tuning relative gene expression in operons is presented. The method constructs libraries of post-­transcriptional regulatory elements that can be cloned into the noncoding sequence between genes. Libraries can be screened to identify sequences that optimize expression of metabolic pathways, multisubunit proteins, or other situations where precise stoichiometric ratios of proteins are desired."

http://bit.ly/ZZjKXx

 

byTarl W. Prow, Daniel Sundh, Gerard A. Lutty "Noninvasive detection of biological responses to reactive oxygen species (ROS) in vivo could shed light on mechanisms at work in diverse areas like developmental dynamics, therapeutic effectiveness, drug discovery, pathogenic processes, and disease prevention. Research on ROS is usually dependent on in vitro models without translational relevance. Nanoscale (<100 nm) particulates are attractive carriers and platforms for biosensor technology due to their small size, flexible assembly, and favorable toxicity profiles. Intracellular signalling pathways activated in response to ROS have been well documented and mechanisms elaborated. Likewise, there is a wealth of genetic reporter systems that utilize fluorescent proteins capable of being monitored noninvasively. We combined these elements into a platform technology that utilizes nanoparticle-tethered synthetic genetic elements that respond to cellular response elements to report endogenous responses to oxidative insult through fluorescent gene expression. We envision the future of this technology to play a research role quantifying oxidative stress in vivo and a future clinical role as an automated theragnostic for ROS-related diseases. The production of this nanobiosensor technology utilizes off-the-shelf components and can be carried out in a molecular biology laboratory. Assessment of fluorescent protein expression can be done with noninvasive imaging and quantitative protein expression analysis. This is a flexible nanoparticle-based reporter system for monitoring in vivo responses to ROS...."http://bit.ly/15U7uqE

by
Hua Jiang , Sayed Ahmad Salehi , Marc D. Riedel , and Keshab K. Parhi

"We present a methodology for implementing discrete-time signal processing operations, such as filtering, with molecular reactions. The reactions produce time-varying output quantities of molecules as a function of time-varying input quantities according to a functional specification. This computation is robust and independent of the reaction rates, provided that the rate constants fall within coarse categories. We describe two approaches: one entails synchronization with a clock signal, implemented through sustained chemical oscillations; the other is “self-timed” or asynchronous. We illustrate the methodology by synthesizing a simple moving-average filter, a biquad filter, and a Fast Fourier Transform (FFT). Abstract molecular reactions for these filters and transforms are translated into DNA strand displacement reactions. The computation is validated through mass-action simulations of the DNA kinetics. Although a proof of concept for the time being, molecular filters and transforms have potential applications in fields such as biochemical sensing and drug delivery."
http://bit.ly/17V03D3

by
DANIELA HERNANDEZ

"The U.S. Supreme Court’s unanimous ruling that naturally occurring genes can’t be patented looks, on the surface, like terrible news for biotech companies. It would appear to strike down thousands of patents claiming intellectual property rights over isolated genetic sequences—the very DNA patents that anchor countless business plans.

 Yet biotech stocks saw a small increase on the Nasdaq Biotechnology Index yesterday, and the effect of the ruling was even more dramatic for Myriad Genetics, the Utah company whose patents were in question. Myriad’s stock price closed up nearly 10 percent, at one point topping $38. That’s the highest since 2009, the year the lawsuit against its patents on BRCA1 and BRCA2, two genes associated with early-onset breast and ovarian cancer, was filed. There’s a reason investors rejoiced over a decision that, superficially, seems to strip so many companies of their most valuable assets. John Wilbanks, chief commons officer at Sage Bionetworks, says that competitive advantage comes not from the DNA data itself but from the ways companies figure out to use it. “It’s clearly not as terrifying a ruling for the industry compared to what it could have been,” Wilbanks said. “It’s a decision that says that data is free, and that’s in line with what patent law has always said, which is that you can’t patent data. That’s what a gene sequence is. “By making that data free, there is a lot of room for public good and public and private innovation.” At the same time, the court did not strike down patents on “new applications of knowledge,” or on DNA whose sequence has been altered. In other words, biotechnologists still have plenty of room to develop proprietary innovations that use DNA data in new ways. Businesses can be build on genetic insights applied to new processes, methods or algorithms, which in most cases would still be patentable....."

http://bit.ly/1aeCtAv*

G8 science ministers endorse open access http://bit.ly/11lJmcJ

 http://bit.ly/19AfvoM

by
Guillermo Rodrigo and Alfonso Jaramillo

"Synthetic regulatory networks with prescribed functions are engineered by assembling a reduced set of functional elements. We could also assemble them computationally if the mathematical models of those functional elements were predictive enough in different genetic contexts. Only after achieving this will we have libraries of models of biological parts able to provide predictive dynamical behaviors for most circuits constructed with them. We thus need tools that can automatically explore different genetic contexts, in addition to being able to use such libraries to design novel circuits with targeted dynamics. We have implemented a new tool, AutoBioCAD, aimed at the automated design of gene regulatory circuits. AutoBioCAD loads a library of models of genetic elements and implements evolutionary design strategies to produce (i) nucleotide sequences encoding circuits with targeted dynamics that can then be tested experimentally and (ii) circuit models for testing regulation principles in natural systems, providing a new tool for synthetic biology. AutoBioCAD can be used to model and design genetic circuits with dynamic behavior, thanks to the incorporation of stochastic effects, robustness, qualitative dynamics, multiobjective optimization, or degenerate nucleotide sequences, all facilitating the link with biological part/circuit engineering."

http://bit.ly/160SRkS

Video: Living Factories: Engineering Cells to Manufacture Molecules http://bit.ly/11cCz8t

by
Gi Na Lee and Jonguk Na 

"Synthetic biology has recently been at the center of the world’s attention as a new scientific and engineering discipline. It allows us to design and construct finely controllable metabolic and regulatory pathways, circuits, and networks, as well as create new enzymes, pathways, and even whole cells. With this great power of synthetic biology, we can develop new organisms that can efficiently produce new drugs to benefit human healthcare and superperforming microorganisms capable of producing chemicals, fuels, and materials from renewable biomass, without the use of fossil oil. Based on several successful examples reported, this commentary aims at peeking into the potential of synthetic biology."


http://bit.ly/18g0Pb4

Provided by American Chemical Society

"The latest episode in the American Chemical Society's (ACS') award-winning Global Challenges/Chemistry Solutions podcast series describes bacteria that are "addicted" to caffeine in a way that promises practical uses ranging from decontamination of wastewater to bioproduction of medications for asthma.Based on a report by Jeffrey Barrick, Ph.D., and colleagues in the journal ACS Synthetic Biology, the new podcast is available without charge at iTunes and from http://www.acs.org/globalchallenges.Some people may joke about living on caffeine, but scientists now have genetically engineered E. coli bacteria to do that—literally.Barrick and colleagues note that caffeine and related chemical compounds have become important water pollutants due to widespread use in coffee, soda pop, tea, energy drinks, chocolate and certain medications. These include prescription drugs for asthma and other lung diseases.The scientists knew that a natural soil bacterium, Pseudomonas putida CBB5, can actually live solely on caffeine and could be used to clean up such environmental contamination. So they set out to transfer genetic gear for breaking down caffeine from P. putida into that old workhorse of biotechnology, E. coli, which is easy to handle and grow.The study reports their success in doing so, as well as use of the E. coli for decaffeination and measuring the caffeine content of beverages. It describes development of a synthetic packet of genes for breaking down caffeine and related compounds that can be moved easily to other microbes. When engineered into certain E. coli, the result was bacteria literally addicted to caffeine.The genetic packet could have applications beyond environmental remediation, the scientists say, citing potential use as a sensor to measure caffeine levels in beverages, in recovery of nutrient-rich byproducts of coffee processing and for the cost-effective bioproduction of medicines..."

http://bit.ly/11HYqnZ

*Craig Venter on Synthetic Life, Genome Sequencing*

Video
"Craig Venter, one of the first scientists to sequence the human genome, spoke to WSJ at the Singularity University conference."

http://on.wsj.com/13V1egq

 http://bit.ly/ZDb5rq

*The exhibition “Yours Synthetically” is all about the thematic topic of synthetic biology* 

by MARTIN HIESLMAIR

"Mr. Gardiner, as we are doing this interview you are collecting artistic works for the next exhibition at the Ars Electronica Center with the English title called “Yours Synthetically” that deals with synthetic biology. Why is this topic so relevant for us nowadays?

 If we look at it purely from the scientific point of view we can say that even from Robert Hooke who used the microscope to discover the cell, the science of biology has continually developed alongside new technologies. The discovery of the double helix and the structure of DNA and all the other milestones of scientific progresses led to the understanding that we could cut and paste genetic information from one organism to another. Early genetic experiments progressed to experiments by modern biologist like Craig Venter, who took a synthetic genome put it into a cell and replaced the old genome that was in the cell, and it started to reproduce. They then examined the new cells and discovered that the synthetic genome had completely replaced the organic one. So to use the computer metaphor – which is quite popular in these studies – we took the hardware of the cell and we changed the software. For a biologist this is very crude. This idea of synthetic biology being an engineering approach to nature – what people find quite frightening – actually is too simplistic. Engineering implies that you know everything that can happen, like you would know that a building will stand even in an earthquake. But how can a synthetic biologist or engineer know what impact of this very long sequence can have on the organism, on the whole environment? The word engineering was kind of being cut out because many people were quite afraid of this – genetic engineering if you remember is what’s called during the past decades. Synthetic biology is partly an attempt by science to reframe this whole field and separate it from the public relations disaster of Genetic Engineering....."

http://bit.ly/15UdZK7