SynBioFromLeukipposInstitute

by Jaimee Saliba

"2012 was a big year for the science of snipping DNA to introduce genetic changes into a cell, also known as genome editing. Though Science magazine hailed two new techniques for selectively cutting and pasting DNA in the field of genome engineering as together constituting one of the Top 10 scientific breakthroughs of the year, those methods may already have been surpassed by researchers at the University of California Berkeley using RNA and a single protein. Faster, simpler, and cheaper, the UCB team led by Dr. Jennifer Doudna published initial results of their work genetically modifying bacteria using the RNA-based DNA cleavage technique last summer. The response from the the life science community was extremely positive, with reviews calling it a "tour de force" and a "a real hit," according to the latest press release. Now three more papers are coming out based on the work of the Doudna Lab showing that the RNA programming technique using a bacterial enzyme known as Cas9 is equally effective in making alterations to human genes..."

http://bit.ly/Y0gE3T

Research in a nutshell:

*Synthetic biology* – *making life better*

by
Chris French

1 min video

"In this video Chris describes how synthetic biology aims to engineer biological systems using modular parts and standardized assembly methods. Applications include biosensors and biocatalysts for novel industrial processes.

Background:

I am a lecturer in the Centre for Synthetic and Systems Biology. Synthetic biology is a new discipline at the interface of biology and engineering. Our aim is to be able to engineer biological systems the same way that engineers build electrical and mechanical systems, using modular parts and standardized assembly methods. To test our ideas, we are working on several different application areas.

One major area is artificial genetic networks. We can build new genetic networks and insert them into a biological system, (ie, a cell) to sense and respond to changes in the environment. I like to think of this as ‘object-oriented genetics’. This can be used, for example, to make biosensors. As a demonstration, we have built a novel biosensor for the detection of arsenic in groundwater, which is a major public health issue in parts of Asia.

Another major focus is the development of novel biocatalysts. One big application area is the conversion of cellulosic biomass to useful products. Cellulosic biomass is very abundant and completely renewable, but it is very hard to convert it to useful things. Some microorganisms in the environment can break down cellulose into its component parts using batteries of enzymes which work together, synergistically, but this kind of system is very difficult to analyse and reproduce. By ‘combinatorial genetic engineering’, we can make a library of genes encoding biomass-degrading enzymes, then assemble many different combinations of these and test them to see which combinations work best for breaking down different types of cellulosic materials. These can then be combined with existing genetic modules for synthesis of useful products such as biofuels.

Other students in my laboratory are working on bacterial stress-response systems, trying to produce genetic modules which will cause organisms to become more resistant to stresses such as solvents and toxic chemicals. This will be very useful for making more robust biocatalysts for industrial applications.

By developing and testing these methods, we are hoping to make it much easier for researchers to develop new biological systems, which can be used for many different applications."
http://bit.ly/WvyTHR

by
Alexander A. Solovev ,  Samuel Sanchez and Oliver G. Schmidt

"Biology widely employs catalytic reactions to power biomotors and cells. These dynamic entities can self-organize into swarms or self-assemble into functional micro- or nanostructures. Synthetic micro-/nanojet engines and nanomotors, driven by catalytic reactions, can move with high power and perform multiple tasks. Collective behavior of these microengines has recently been observed which includes swarming activities and the formation of multiconstituent entities. This feature article discusses recent developments, presents new discoveries on collective motion of self-propelled microjet engines and suggests next steps to undertake in the field of collective micromachines."

http://rsc.li/VLlXiC

by
Leslie Lang-UNC

"Snippets of information contained in dark matter, or “junk DNA,” can alter the way a gene gets put together, according to new research.
“These small sequences of genetic information tell the gene how to splice, either by enhancing the splicing process or inhibiting it. The research opens the door for studying the dark matter of genes. And it helps us further understand how mutations or polymorphisms affect the functions of any gene,” says study senior author Zefeng Wang, assistant professor of pharmacology in the University of North Carolina School of Medicine."
http://bit.ly/XNHooo

comment to:

*A complex network of factors with overlapping affinities represses splicing through intronic elements*

by
Yang Wang,Xinshu Xiao,Jianming Zhang,Rajarshi Choudhury,Alex Robertson,Kai Li, Meng Ma,Christopher B Burge& Zefeng Wang

"To better understand splicing regulation, we used a cell-based screen to identify ten diverse motifs that inhibit splicing from introns. Motifs were validated in another human cell type and gene context, and their presence correlated with in vivo splicing changes. All motifs exhibited exonic splicing enhancer or silencer activity, and grouping these motifs according to their distributions yielded clusters with distinct patterns of context-dependent activity. Candidate regulatory factors associated with each motif were identified, to recover 24 known and new splicing regulators. Specific domains in selected factors were sufficient to confer intronic-splicing-silencer activity. Many factors bound multiple distinct motifs with similar affinity, and all motifs were recognized by multiple factors, which revealed a complex overlapping network of protein-RNA interactions. This arrangement enables individual cis elements to function differently in distinct cellular contexts, depending on the spectrum of regulatory factors present."

http://bit.ly/VHpsqg

by Kevin Stacey-Brown 

" When single molecules of DNA zip through nanopores, they most often travel head first. Physicists working toward nanopore sequencing devices say a “Jell-O theory” explains why. 

According to the new study, the DNA molecules have a convenient tendency to cooperate.The research, published in the journal Physical Review Letters, looks at the dynamics of how DNA molecules are captured by solid-state nanopores, tiny holes that soon may help sequence DNA at lightning speed. The study finds that when a DNA strand is captured and pulled through a nanopore, it’s much more likely to start the journey at one of its ends, rather than being grabbed somewhere in the middle and pulled through in a folded configuration.“We think this is an important advance for understanding how DNA molecules interact with these nanopores,” says Derek Stein, assistant professor of physics at Brown University, who performed the research with graduate students Mirna Mihovilivic and Nick Haggerty.“If you want to do sequencing or some other analysis, you want the molecule going through the pore head to tail.”Research into DNA sequencing with nanopores started a little over 15 years ago. The concept is fairly simple. A little hole, a few billionths of a meter across, is poked in a barrier separating two pools of salt water. An electric current is applied across the hole, which occasionally attracts a DNA molecule floating in the water.When that happens, the molecule is whipped through the pore in a fraction of a second. Scientists can then use sensors on the pore or other means to identify nucleotide bases, the building blocks of the genetic code.The technology is advancing quickly, and the first nanopore sequencing devices are expected to be on the market very soon. But there are still basic questions about how molecules behave at the moment they’re captured and before.“What the molecules were doing before they’re captured was a mystery and a matter of speculation,” Stein says. “And we’d like to know because if you’re trying to engineer something to control that molecule—to get it to do what you want it to do—you need to know what it’s up to....."

http://bit.ly/U47BdJ

by
Anna H. Chen, Pamela A. Silver

"Intracellular organization is a key factor in cell metabolism. Cells have evolved various organizational systems to solve the challenges of toxic pathway intermediates, competing metabolic reactions, and slow turnover rates. Inspired by nature, synthetic biologists have utilized proteins, nucleic acids, and lipids to construct synthetic organizational systems that mimic natural systems. Many of these systems have been applied to metabolic pathways and shown to significantly increase the production of industrially and commercially important chemicals. Further engineering and characterization of synthetic organizational systems will allow us to better understand native cellular strategies of spatial organization. Here, we discuss recent advances and ongoing efforts in designing and characterizing synthetic compartmentalization systems to mimic natural strategies and increase metabolic yields of engineered pathways."

http://bit.ly/Zhb8p3

 
by
Brian S. Goodman, Nathan D. Derr, Samara L. Reck-Peterson

"Synthetic biology re-imagines existing biological systems by designing and constructing new biological parts, devices, and systems. In the arena of cytoskeleton-based transport, synthetic approaches are currently used in two broad ways. First, molecular motors are harnessed for non-physiological functions in cells. Second, transport systems are engineered in vitro to determine the biophysical rules that govern motility. These rules are then applied to synthetic nanotechnological systems. We review recent advances in both of these areas and conclude by discussing future directions in engineering the cytoskeleton and its motors for transport."

http://bit.ly/XE1ZLE

Technology is by itself value neutral, and can be both used for the good or the bad. Thus, new technology as Synthetic Biology needs a broad public discussion about the finalization of this kind of research!

*Synthetic biology*: *Social and ethical challenges*

by
Andrew Balmer & Paul Martin

".....This report therefore aims to briefly review the main social and ethical issues raisedin public debates about synthetic biology. In particular, it draws on media reports,academic publications and grey literature mostly published in the last five years. Thefirst two sections provide some definitions of synthetic biology and summarise thecentral areas of scientific research. This is followed by a description of how thescience and technology has developed in recent years, the emergence of publicdebate about its implications and the policy response to these concerns in a numberof key areas. Finally, some reflections on the lessons that might be learnt from theearlier debates over genetic engineering and recommendations for policy are offeredin the conclusion
http://bit.ly/WmjZUq

By Christie Rizk 

"When geneticist Craig Venter announced that his team had constructed a self-replicating bacterial genome from scratch in May 2010, University of California, Berkeley anthropologist Paul Rabinow told the journal Science that "this experiment will certainly reconfigure the ethical imagination."

As a new scientific era unfolds in which life can be synthesized in various forms to serve a variety of purposes, Rabinow's prediction is becoming reality. In response to Venter's achievement, President Obama asked the Presidential Commission for the Study of Bioethical Issues to recommend an ethical framework for research in the field of synthetic biology that would maximize public benefit while minimizing risk. The Commission's December 2010 report concluded that "synthetic biology offers extraordinary promise to create new products for clean energy, pollution control, and medicine, to revolutionize chemical production and manufacturing, and to create new economic opportunities." And it recommended ways the private and public sectors could work together to determine appropriate oversight without limiting the field's potential. Since then, opposition to synthetic biology has come from several sectors. Some religious groups say scientists in the field are playing God, creating life that isn't theirs to create. Some environmental groups have expressed misgivings about the possible chaos a synthetic life form could unleash if released from the lab. And the potential for misuse of the technology for bioterrorism is a concern of citizens and scientists alike....."

 http://bit.ly/13aiqPf

 

byBartosz Lewandowski, Guillaume De Bo, John W. Ward, Marcus Papmeyer, Sonja Kuschel, María J. Aldegunde, Philipp M. E. Gramlich, Dominik Heckmann, Stephen M. Goldup, Daniel M. D’Souza, Antony E. Fernandes, David A. Leigh "The ribosome builds proteins by joining together amino acids in an order determined by messenger RNA. Here, we report on the design, synthesis, and operation of an artificial small-molecule machine that travels along a molecular strand, picking up amino acids that block its path, to synthesize a peptide in a sequence-specific manner. The chemical structure is based on a rotaxane, a molecular ring threaded onto a molecular axle. The ring carries a thiolate group that iteratively removes amino acids in order from the strand and transfers them to a peptide-elongation site through native chemical ligation. The synthesis is demonstrated with ~1018 molecular machines acting in parallel; this process generates milligram quantities of a peptide with a single sequence confirmed by tandem mass spectrometry." http://bit.ly/V1suHr see also *Towards a molecular factory*: *Processive sequence-selective synthesis with a synthetic molecular machine* byDavid Leigh ""The widespread use of molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems—which by and large rely upon electronic and chemical effects to carry out their functions—and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform particular tasks.1 In recent years it has proved possible to design synthetic molecular systems where positional changes of submolecular components occur by moving energetically downhill but many questions in this field remain unanswered: What are the structural features necessary for molecules to use chemical energy to repetitively do useful work at the molecular level? Artificial compounds that can do these things have yet to be realized; the field of synthetic molecular machines is still very much in its infancy and only the most basic systems—mechanical switches and slightly more sophisticated, but still rudimentary, molecular rotors—have been made thus far. The aim of this project is to construct and demonstrate the successful operation of synthetic molecular machines capable of performing complex tasks, far beyond the current state-of-the-art.Our target is to mimic translation, the process through which protein is synthesized on the mRNA template in the ribosome. To achieve this ambitious task (in a very basic form) through the action of a wholly artificial molecular machine system (Figure 1) we propose to utilise a [2]rotaxane in which the macrocycle component acts as both a catalyst and a molecular transporter, abstracting bulky aromatic amino acid substituents from a sequence-specific ‘thread’ and transporting them in turn to the next amino acid fragment before mediating the formation of a new amide bond between them. The design is such that the macrocycle is forced to approach each amino acid in sequence, and is unable to pass until the cycle is complete, imparting sequential integrity to the oligopeptide synthesis. The mechanically interlocked nature of the rotaxane ensures processivity during the machine’s operation. Although biology uses threaded molecular architectures to transfer chemical information during sequence-specific oligomer and polymer assembly (proteins, oligo- and polysaccharides, DNA and RNA), such effects are unprecedented in artificial systems. We hope that our synthetic studies will provide a breakthrough in the development of artificial molecular machines that can perform real tasks at the molecular level including, ultimately, the synthesis of unnatural sequence-specific oligomers and polymers that are not accessible by other routes."http://bit.ly/XqprrP  ;

Computing is about to get really personal.  On your Finger.....In your face.....On your wrist....Atop your head....On your Skin.....In your pocket.....Inside you..... "We’ve been hearing about “wearable computing” for years. But we’re finally at a tipping point. Better batteries, miniaturization, and radical new approaches to manufacturing electronic circuits have finally made screens, computers and sensors small enough to stick just about anywhere. It no longer seems strange to see someone wearing a bracelet that records their vital signs, a watch with as much power as a cell phone, or, soon to be available, glasses that augment our reality. Smartphones are the key to this trend. Now that we’re all carrying powerful general-purpose computers on our person, which are in easy radio range of whatever other devices we might carry, we’re creating our own personal, local cloud-computing networks. Our phones are like brains, and everything from our wireless headsets to our heart-rate monitors are their distributed nervous system. It sounds crazy, but the cyborgification of humanity is proceeding apace. It will change how we live and how we work, and for the same reason that none of us can put down our mobile devices, we will be powerless to resist. This year’s Consumer Electronics Show (CES) is flush with so-called “smart watches,” but other kinds of wearable computer that you’ve probably never heard of are also about to take off. Here’s a brief tour through the Internet of You.......MC10′s “biostamps” embed its flexible circuitry in plastic that can be stuck to human skin like a temporary tattoo. The result are sensors for heart rate, perspiration, impact, and so on that can record data that can later be read by RFID—the same technology that enables tap-to-pay systems on key fobs and mobile wallets. No wonder the company just got another $10 million in a series C round of financing.......When I interviewed one of the engineers behind MC10′s flexible circuits, he told me that one of his goals was to eventually create an artificial pericardium—the sack that surrounds the heart—and infuse it with a mesh of his flexible circuits, all firing in a precise and reactive way, to act like a much more sophisticated and precise pacemaker for a diseased heart. Already, MC10 has created a prototype balloon catheter equipped with sensors that can measure electrical misfiring caused by cardiac arrhythmias. Taken together, these devices represent something consumers have never really seen before—a body-based network of input and output devices that travels with us wherever we go. If it’s hard to imagine how any one of them might change our lives, what’s completely unpredictable is what they’ll do when combined. It’s exactly the sort of opportunity the consumer-electronics industry needs to lift it out of its doldrums. And the companies that can capitalize on that will be entering an industry with tremendous room for growth—because it doesn’t really exist yet." http://bit.ly/SojduM ;

by
Yen-Ting Lai, Neil P. King, Todd O. Yeates

"In nature, many proteins have evolved to have self-complementary shapes. This drives them to assemble into supramolecular structures, sometimes of great complexity, and often carrying out sophisticated cellular functions. Designing novel proteins that can self-assemble into similarly complex structures is a longstanding goal in bioengineering. New ideas, combined with continually improving computer algorithms, are making it possible to advance on that goal, bringing wide-ranging applications in synthetic biology within reach. Prospective applications range from vaccine design to molecular delivery to bioactive materials. Recent strategies and examples of successfully designed protein cages, layers, and crystals are reviewed."

http://bit.ly/XE3NEt

"Optogenetics is the integration of optics and genetics to control precisely defined events within specific cells of living tissue"
http://en.wikipedia.org/wiki/Optogenetics

*How to 'take over' a brain* ?

by
Leonard Mlodinow

"The hottest field in science this past decade has been neuroscience. That explosion in research, and our understanding of the human brain, was largely fueled by a new technology called functional magnetic resonance imaging (fMRI) that became widely available in the 1990s. Well look out! Another technology-based neuroscience revolution is in the making, this one perhaps even bigger. The term to watch for in 2013 is "optogenetics." It's not a sexy term, but it is a very sexy technology."
http://bit.ly/UABClc

see also:
*Optogenetics: controlling cell function with light*

by
Erika Pastrana

"A brief description of the basic steps required to control cellular function with optogenetics is presented."
http://bit.ly/VEi6WJ