"Cell-free systems offer a simplified and flexible context that enables important biological reactions while removing complicating factors such as fitness, division, and mutation that are associated with living cells. However, cell-free expression in unconfined spaces is missing important elements of expression in living cells. In particular, the small volume of living cells can give rise to significant stochastic effects, which are negligible in bulk cell-free reactions. Here, we confine cell-free gene expression reactions to cell-relevant 20 fL volumes (between the volumes of E. coli and S. cerevisiae), in polydimethylsiloxane (PDMS) containers. We demonstrate that expression efficiency varies widely among different containers, likely due to non-Poisson distribution of expression machinery at the observed scale. Previously, this phenomenon has been observed only in liposomes. In addition, we analyze gene expression noise. This analysis is facilitated by our use of cell-free systems, which allow the mapping of the measured noise properties to intrinsic noise models. In contrast, previous live cell noise analysis efforts have been complicated by multiple noise sources. Noise analysis reveals signatures of translational bursting while noise dynamics suggest that overall cell-free expression is limited by a diminishing translation rate. In addition to offering a unique approach to understanding noise in gene circuits, our work contributes to a deeper understanding of the biophysical properties of cell-free expression systems, thus aiding efforts to harness cell-free systems for synthetic biology applications."
"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."
by Javier A Gimpel, Elizabeth A Specht, D Ryan Georgianna, Stephen P Mayfield
"Among the technologies being examined to produce renewable fuels, microalgae are viewed by many in the scientific community as having the greatest potential to become economically viable. Algae are capable of producing greater than 50,000 kg/acre/year of biomass . Additionally, most algae naturally accumulate energy-dense oils that can easily be converted into transportation fuels. To reach economic parity with fossil fuels there are still several challenges. These include identifying crop protection strategies, improving harvesting and oil extraction processes, and increasing biomass productivity and oil content. All of these challenges can be impacted by genetic, molecular, and ultimately synthetic biology techniques, and all of these technologies are being deployed to enable algal biofuels to become economically competitive with fossil fuels."
*Is This Virtual Worm the First Sign of the Singularity?*
by ALEXIS C. MADRIGAL
"For all the talk of artificial intelligence and all the games of SimCity that have been played, no one in the world can actually simulate living things. Biology is so complex that nowhere on Earth is there a comprehensive model of even a single simple bacterial cell.
And yet, these are exciting times for "executable biology," an emerging field dedicated to creating models of organisms that run on a computer. Last year, Markus Covert's Stanford lab created the best ever molecular model of a very simple cell. To do so, they had to compile information from 900 scientific publications. An editorial that accompanied the study in the journal Cell was titled, "The Dawn of Virtual Cell Biology." In January of this year, the one-billion euro Human Brain Project received a decade's worth of backing from the European Union to simulate a human brain in a supercomputer. It joins Blue Brain, an eight-year-old collaboration between IBM and the Swiss Federal Institute of Technology in Lausanne, in this quest. In an optimistic moment in 2009, Blue Brain's director claimed such a model was possible by 2019. And last month, President Obama unveiled a $100 million BRAIN Initiative to give "scientists the tools they need to get a dynamic picture of the brain in action." An entire field, connectomics, has emerged to create wiring diagrams of the connections between neurons ("connectomes"), which is a necessary first step in building a realistic simulation of a nervous system. In short, brains are hot, especially efforts to model them in silico. But in between the cell-on-silicon and the brain-on-silicon simulators lies a fascinating and strange new project to create a life-like simulation of Caenohabditis elegans, a roundworm. OpenWorm isn't like these other initiatives; it's a scrappy, open-source project that began with a tweet and that's coordinated on Google Hangouts by scientists spread from San Diego to Russia. If it succeeds, it will have created a first in executable biology: a simulated animal using the principles of life to exist on a computer..."
"Programmed death is often associated with a bacterial stress response. This behavior appears paradoxical, as it offers no benefit to the individual. This paradox can be explained if the death is `altruistic': the sacrifice of some cells can benefit the survivors through release of `public goods'. However, the conditions where bacterial programmed death becomes advantageous have not been unambiguously demonstrated experimentally. Here, I determined such conditions by engineering tunable, stress-induced altruistic death in the bacterium Escherichia coli. Using a mathematical model, we predicted the existence of an optimal programmed death rate that maximizes population growth under stress. I further predicted that altruistic death could generate the `Eagle effect', a counter-intuitive phenomenon where bacteria appear to grow better when treated with higher antibiotic concentrations. In support of these modeling insights, I experimentally demonstrated both the optimality in programmed death rate and the Eagle effect using our engineered system. These findings fill a critical conceptual gap in the analysis of the evolution of bacterial programmed death, and have implications for a design of antibiotic treatment"
Synthetic biology moves us from reading to writing DNA, allowing us to design biological systems from scratch for any number of applications. Its capabilities are becoming clearer, its first products and processes emerging.
*New Mechanism of Self-Assembly from DNA-Tethered Nanorods*
by Karen McNulty Walsh, Peter Genzer
"Approach could be useful in fabricating new kinds of materials with engineered properties
UPTON, NY—Scientists at the U.S. Department of Energy's Brookhaven National Laboratory have discovered that DNA "linker" strands coax nano-sized rods to line up in a way unlike any other spontaneous arrangement of rod-shaped objects. The arrangement—with the rods forming "rungs" on ladder-like ribbons linked by multiple DNA strands—results from the collective interactions of the flexible DNA tethers and may be unique to the nanoscale. The research, described in a paper published online in ACS Nano, a journal of the American Chemical Society, could result in the fabrication of new nanostructured materials with desired properties. "This is a completely new mechanism of self-assembly that does not have direct analogs in the realm of molecular or microscale systems," said Brookhaven physicist Oleg Gang, lead author on the paper, who conducted the bulk of the research at the Lab's Center for Functional Nanomaterials (CFN)...."
Zhen Gu †‡§¶, Alex A. Aimetti †‡§, Qun Wang †‡,Tram T. Dang †‡, Yunlong Zhang †‡§, Omid Veiseh†‡§, Hao Cheng †‡#, Robert S. Langer †‡§, andDaniel G. Anderson †‡§*
"Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivostudies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days."
"Synthetic biology has significantly advanced the design of synthetic control devices, gene circuits and networks that can reprogram mammalian cells in a trigger-inducible manner. Prokaryotic helix-turn-helix motifs have become the standard resource to design synthetic mammalian transcription factors that tune chimeric promoters in a small molecule-responsive manner. We have identified a family of Actinomycetes transcriptional repressor proteins showing a tandem TetR-family signature and have used a synthetic biology-inspired approach to reveal the potential control dynamics of these bi-partite regulators. Daisy-chain assembly of well-characterized prokaryotic repressor proteins such as TetR, ScbR, TtgR or VanR and fusion to either the Herpes simplex transactivation domain VP16 or the Krueppel-associated box domain (KRAB) of the human kox-1 gene resulted in synthetic bi- and even tri-partite mammalian transcription factors that could reversibly program their individual chimeric or hybrid promoters for trigger-adjustable transgene expression using tetracycline (TET), γ-butyrolactones, phloretin and vanillic acid. Detailed characterization of the bi-partite ScbR-TetR-VP16 (ST-TA) transcription factor revealed independent control of TET- and γ-butyrolactone-responsive promoters at high and double-pole double-throw (DPDT) relay switch qualities at low intracellular concentrations. Similar to electromagnetically operated mechanical DPDT relay switches that control two electric circuits by a fully isolated low-power signal, TET programs ST-TA to progressively switch from TetR-specific promoter-driven expression of transgene one to ScbR-specific promoter-driven transcription of transgene two while ST-TA flips back to exclusive transgene 1 expression in the absence of the trigger antibiotic. We suggest that natural repressors and activators with tandem TetR-family signatures may also provide independent as well as DPDT-mediated control of two sets of transgenes in bacteria, and that their synthetic transcription-factor analogs may enable the design of compact therapeutic gene circuits for gene and cell-based therapies."
by Marjon GJ de Vos, Frank J Poelwij1, Sander J Tans
"Whether organisms evolve to perform tasks optimally has intrigued biologists since Lamarck and Darwin. Optimality models have been used to study diverse properties such as shape, locomotion, and behavior. However, without access to the genetic underpinnings or the ability to manipulate biological functions, it has been difficult to understand an organism's intrinsic potential and limitations. Now, novel experiments are overcoming these technical obstacles and have begun to test optimality in more quantitative terms. With the use of simple model systems, genetic engineering, and mathematical modeling, one can independently quantify the prevailing selective pressures and optimal phenotypes. These studies have given an exciting view into the evolutionary potential and constraints of biological systems, and hold the promise to further test the limits of predicting future evolutionary change."
*If there is a professional communicator* (broadcaster, author, teacher/FE lecturer, artist etc.) *who has done brilliant work* relating to applied microbiology (e.g. brewing, *synthetic biology*, bioenergy, hospital acquired infections, wound healing, antibiotics, food poisoning, the spread of infectious diseases), you can nominate them. Or perhaps you are a professional communicator and you would like to nominate yourself. The winner will receive £500 in recognition of their work.
*Flu vaccines and synthetic biology - Going viral*
By The Econnomist
"A speedy way to make a vaccine
IF A new and deadly strain of influenza were to arise, putting together a vaccine against it in the least possible time would be a priority. To test how quickly that could be done a group of researchers have just had a race with themselves. They have not quite matched the show sometimes given by workers at the Venetian arsenal, who would assemble a galley in a single day in order to overawe visiting foreign dignitaries. But Philip Dormitzer, Craig Venter and their colleagues did create the crucial component of a flu jab in four days and four hours. Dr Dormitzer, who works for Novartis, a drug company, and Dr Venter, eponymous founder of the J. Craig Venter Institute in San Diego, reported their record-breaking attempt in this week’s Science Translational Medicine. It began with the transmission to them from America’s Biomedical Advanced Research and Development Authority of the sequence data for the haemagglutinin and neuraminidase genes of a (to them) unknown flu virus......." http://econ.st/13Db7kB
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