SynBioFromLeukipposInstitute

 http://bit.ly/10xqVVK

by
Brewster RC, Jones DL, Phillips R.

"One of the paramount goals of synthetic biology is to have the ability to tune transcriptional networks to targeted levels of expression at will. As a step in that direction, we have constructed a set of [Formula: see text] unique binding sites for E. coli RNA Polymerase (RNAP) [Formula: see text] holoenzyme, designed using a model of sequence-dependent binding energy combined with a thermodynamic model of transcription to produce a targeted level of gene expression. This promoter set allows us to determine the correspondence between the absolute numbers of mRNA molecules or protein products and the predicted promoter binding energies measured in [Formula: see text] energy units. These binding sites adhere on average to the predicted level of gene expression over [Formula: see text] orders of magnitude in constitutive gene expression, to within a factor of [Formula: see text] in both protein and mRNA copy number. With these promoters in hand, we then place them under the regulatory control of a bacterial repressor and show that again there is a strict correspondence between the measured and predicted levels of expression, demonstrating the transferability of the promoters to an alternate regulatory context. In particular, our thermodynamic model predicts the expression from our promoters under a range of repressor concentrations between several per cell up to over [Formula: see text] per cell. After correcting the predicted polymerase binding strength using the data from the unregulated promoter, the thermodynamic model accurately predicts the expression for the simple repression strains to within [Formula: see text]. Demonstration of modular promoter design, where parts of the circuit (such as RNAP/TF binding strength and transcription factor copy number) can be independently chosen from a stock list and combined to give a predictable result, has important implications as an engineering tool for use in synthetic biology."

 http://bit.ly/UAocYa

Video/TEDx talk
by
Rodrigo Martinez

"Imagine living in a building that was not constructed, but 'grown;' or imagine designing your own shirt, printing it while you take a shower and recycling it at night...every day. Who makes all the things we use and how these are made is about to change dramatically. Rodrigo Martinez believes that we are in the early stages of a new revolution that will affect every design, manufacturing and industrial process around us - "If you want to be part of some of the most exciting things that will take place in the coming decades, become a biohacker!" 

Rodrigo Martinez, Life Sciences Chief Strategist at award-winning design firm IDEO, explores the opportunities at the crossroads of design + biology to envision future products and services."


http://bit.ly/VbayZ4

by
Joerg Mampel, Joerg Martin Buescher, Guido Meurer, Juergen Eck

"In the past decade, systems biology has revealed great metabolic and regulatory complexity even in seemingly simple microbial systems. Metabolic engineering aims to control this complexity in order to establish sustainable and economically viable production routes for valuable chemicals. Recent advances in systems-level data generation and modeling of cellular metabolism and regulation together with tremendous progress in synthetic biology will provide the tools to put biotechnologists on the fast track for implementing novel production processes. Great potential lies in the reduction of cellular complexity by orthogonalization of metabolic modules. Here, we review recent advances that will eventually enable metabolic engineers to predict, design, and build streamlined microbial cell factories with reduced time and effort."

 http://bit.ly/TJg1u1

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 medicine.

47 min Video: Craig Venter: 

*The software of life'*

"Sir David Frost meets the scientist who first sequenced the human genome and went on to create artificial life.

When Craig Venter announced in 2000 that he had mapped the human genome - the genetic material that uniquely identifies each individual - it was the sort of blockbuster announcement that comes once in a generation, and it established Venter as one of the most influential scientists on the planet. "For the first time now we can actually design life in a computer, make the DNA software and create new life forms that have never existed before." Since then, in addition to further research on the genome, Venter has sailed the world, exploring new life forms and applying this knowledge to another pursuit heretofore dreamed of only in science fiction: the creation of life itself in a laboratory, which he accomplished in 2010. Venter has also been tackling the problem of climate change by inventing new methods of carbon collection and alternative energy sources, particularly by growing new forms of algae that not only grab carbon from the atmosphere but can themselves be used to produce oil for fuel. Sir David Frost visits Venter in his laboratory near San Diego, California, where he learns that Craig began his adult life as an indifferent student turned beach bum before enlisting in the US navy at the height of the Vietnam War, where he worked in the intensive care ward of a field hospital. Venter takes Sir David for a drive in his all-electric Tesla car, and tells of such encounters as the time he informed Bill Clinton that the former US president was, genetically-speaking, three percent Neanderthal..."

http://aje.me/VhmsQl

by
BRSM

"I think most would agree that synthetic chemists can now make just about any non-protein/non-polysaccharide natural product if enough time, resources and manpower are brought to bear.[1] But that's not to say that the field is yet mature, or stagnating, as there still remain so many challenges to make our science more efficient, practical, and free from its current over-dependence on rare metals and petrochemical feedstocks. Recently, synthetic biology has started to emerge as a serious alternative to total synthesis when large amounts of complex natural products are required. Just think how many total synthesis papers start with a desultory line about 'the dearth of natural material', before recounting an arduous one- or two-yearlong quest to make a few more milligrams of the compound in question. Perhaps it sometimes makes more sense to try a different approach and ask 'can't we just improve the natural source?'. We synthetic chemists like to think we're special because we have the ability to make new compounds never seen in Nature, but with an increasing understanding of enzymes and the genes that encode for them, organisms can now be coaxed into producing compounds that have never been seen before. If you're interested in reading further debate over the future of the two fields then you should definitely read this short piece in Nature, in which champions of synthetic chemistry Phil Baran and Abraham Mendoza duke it out with Jay D. Keasling, a strong proponent of synthetic biology."
http://bit.ly/jqZkwN

ref:

*Synthesis*: *A constructive debate*ByJay D. Keasling, Abraham Mendoza & Phil S. Baran
"Synthetic chemistry has long been used to prepare useful compounds — especially those that are hard to obtain from natural sources. But synthetic biology is coming of age as an alternative strategy. A biologist and two chemists debate the merits of their fields' synthetic prowess."
http://bit.ly/W4Urkc

"Magnetic Bacteria Computers*

"Magnet-making bacteria may be building biological computers of the future, researchers have said.

 A team from the UK's University of Leeds and Japan's Tokyo University of Agriculture and Technology have used microbes that eat iron. As they ingest the iron, the microbes create tiny magnets inside themselves, similar to those in PC hard drives. The research may lead to the creation of much faster hard drives, the team of scientists say. The study appears in the journal Small. As technology progresses and computer components get smaller and smaller, it becomes harder to produce electronics on a nano-scale. So researchers are now turning to nature - and getting microbes involved. Magnetic bacteriaIn the current study, the scientists used the bacterium Magnetospirilllum magneticum. These naturally magnetic microorganisms usually live in aquatic environments such as ponds and lakes, below the surface where oxygen is scarce. Continue reading the main story“Start Quote We are quickly reaching the limits of traditional electronic manufacturing as computer components get smaller... Nature has provided us with the perfect tool to [deal with] this problem” Dr Sarah StanilandUniversity of LeedsThey swim following the Earth's magnetic field lines, aligning in the magnetic field like compass needles, in search of preferred oxygen concentrations...."

 http://bbc.in/W1PaEf

By
Science 2.0

"Researchers have fabricated an artificial protein in the laboratory and examined the ways living cells respond to it. 

   The research results describe a peculiar set of adaptations exhibited by Escherichia coli bacterial cells exposed to a synthetic protein, dubbed DX. Inside the cell, DX proteins bind with molecules of ATP, the energy source required by all biological entities.  After exposure to DX, the normally spherical E. coli bacteria develop into elongated filaments. Within the filamentous bacteria, dense intracellular lipid structures act to partition the cell at regular intervals along its length (see figure 1). These unusual structures, which the authors call endoliposomes, are an unprecedented phenomenon in such cells.   The phosphodiester bonds of ATP contain the energy necessary to drive reactions in living systems, giving up their stored energy when these bonds are chemically cleaved. The depletion of available intracellular ATP by DX binding disrupts normal metabolic activity in the cells, preventing them from dividing, though they continue to grow.  "ATP is the energy currency of life," says study co-author John Chaput, a researcher at Arizona State University's Biodesign Institute. "Somewhere along the line of this filamentation, other processes begin to happen that we haven't fully understood at the genetic level, but we can see the results phenotypically. These dense lipid structures are forming at very regular regions along the filamented cell and it looks like it could be a defense mechanism, allowing the cell to compartmentalize itself." ..."

http://bit.ly/W7Kpco

"On the last day of this year, outliving the universe by 10 days if the Mayan calendar was correct, the print edition of Newsweek will be no more, making the 80-year-old dentist's waiting-room staple the latest in a long line of victims of changing reader habits, the high cost of print and a Darwinian newsstand.....

Put another way, all of our "likes" and retweets set the country's agenda more than a powerful editor's feature selection could....."

We really see an end of an era of publishing. The dead of the journal.... and it is good, This format worked well in another cultural context. They have been awesome, and some people have really done outstanding work...However, we reached the digital age.

This is also true for scientific publishing. I see it myself, my social networks working awesome to find outstanding science blogs... Crowd sourcing (incl likes and all form of retweeting) are superior to the work any editor can achieve.  We have a new speed in publishing. Real time publishing on blogs are on the way to substitute the journal.

The publishing industry is under major change. Some major publications are already dead, many will follow.

What does this mean for science?

The academic scientist lives from a business model based on publication in high impact journals. These publications are the base for a tax payer financed position. As scientist are normally at the cutting edge, they are very conservative in respect to modern publishing formats. The main reason behind this is a rightful fear for the own career. As the business model for the traditional journal do not work any longer, it is time that scientists start a discussion of how to adapt to the new times. 

Functional models are existing (eg scientific blogs, real time publications, post publication review, open lab books...) The major question to solve is the social agreement of hoe we wish to continue. How will we measure performance as a foundation for a career? 

We really need to discuss this.


ref
http://bit.ly/RnhdBp

47 min video
by
Wired

"Craig Venter, CEO & President, Synthetic Genomics, shares the latest advancements in synthetic genomic research and technology. According to Venter, synthetic biological organisms" 

http://bit.ly/U6SeAF

 One approach to understanding components in living organisms is to attempt to create them artificially, using principles of chemistry, engineering and genetics. A suite of powerful techniques -- collectively referred to as synthetic biology -- have been used to produce self-replicating molecules, artificial pathways in living systems and organisms bearing synthetic genomes.

by
Michael Eisenstein

"Self-assembling DNA nanopores could offer a powerful, customizable tool for a host of biological applications.

Scientists looking to manage molecular movement for biotechnology applications are increasingly turning to protein pores, whose structure has naturally evolved for such functions. For example, the Staphylococcus aureus channel protein α-hemolysin is used in DNA sequencing technology as well as various biosensor platforms. Unfortunately, proteins offer limited opportunities for customization. “You might be able to do some point mutations here and there, but you cannot globally alter the geometry of the channel,” explains Hendrik Dietz. Dietz has been pursuing an alternative approach to biological devices, designing DNA scaffolds that self-assemble into complex, three-dimensional nanostructures—so-called 'DNA origami'. Dietz recently teamed up with Friedrich Simmel, his neighbor down the hall at Germany's Technische Universität München, who has also amassed considerable experience with DNA-based nanomachines and spent the past several years studying nanopore biology. By pooling their expertise, their two groups were able to construct entirely DNA-based nanopores that automatically insert themselves into lipid bilayers. They computationally designed a set of DNA strands that hybridize to form a syringe-shaped structure with a 2-nanometer-diameter channel running down the middle. The 'needle' of the syringe is intended to penetrate the membrane, and the researchers tagged the strands at the membrane-facing side of the 'barrel' with cholesterol molecules to help the nanostructure adhere tightly in the proper orientation. According to Dietz, the construction process was straightforward. “We have a fabrication method that allows us to make structures within an hour with nearly 100% yield,” he says, and the researchers were able to observe evidence for proper assembly via electron microscopy. Confirmation that the nanopores were functioning as intended, however, required an extensive and time-consuming series of electrophysiology experiments. Fortunately, these showed that the nanopores not only had pierced the membrane but also were capable of transmitting electrical current across the lipid bilayer......"

http://bit.ly/V8VUBF

by
Jeffrey M Perkel

"Yogurt. Comedian George Carlin wouldn't touch it; Spaceballs villain “Dark Helmet” “hated” it—even with strawberries. But Boston University biomedical engineer James Collins, a Howard Hughes Medical Institute Investigator, has recently been giving the fermented dairy treat a great deal of thought. Not how his preferred flavor, vanilla, tastes atop granola, nor how plain yogurt and dill pair perfectly with salmon. For Collins, yogurt—or, more precisely, the lactobacilli that make yogurt yogurt—could potentially be the answer to a vexing public health problem: cholera.

 Collins is a pioneer in the burgeoning field of synthetic biology, the science of reprogramming cells with novel biological functions, from biosensors to antimicrobials to biofuels. The field, writes Harvard Medical School geneticist George Church, capitalizes on the fact that biological organisms are effectively programmable manufacturing systems. In this context, cells serve as miniature computers, programmed toward a new purpose with externally supplied genetic instructions. Church notes that “making small changes in their genetic software a bioengineer can effect big changes in their output”1. In Collins's case, the big change he hopes to effect converts yogurt cultures into microbial sentries against Vibrio cholerae, the pathogen that causes cholera. Supported by a grant from the Bill and Melinda Gates Foundation, Collins wants to harness the pathogen's own biochemistry against it. His team is working to genetically reprogram yogurt bacteria to recognize the small molecules that the cholera bacteria use to communicate and sense their environment, in a process called “quorum sensing,” and pump out anti-cholera peptides in response. “You've got basically now a little bug that could become your instant pharmacy to respond to the infection,” says Collins. To do their protective job,..."

 http://bit.ly/VhiVBp

Video
by 
Weizmann Institute of Science

"A group of scientists headed by Prof. Ehud Shapiro at the Weizmann Institute of Science has used biological molecules to create a tiny computer - a programmable two-state, two-symbol finite automaton - in a test tube. This biological nanocomputer is so small that a trillion (1,000,000,000,000) such computers co-exist and compute in parallel, in a drop the size of 1/10 of a milliliter of watery solution held at room temperature. Collectively, the computers perform a billion operations per second with greater than 99.8% accuracy per operation while requiring less than a billionth of a Watt of power. This study may lead to future computers that can operate within the human body, interacting with its biochemical environment to yield far-reaching biological and pharmaceutical applications."


 http://bit.ly/TjrEWg