Ralf Steuer, Steffen Waldherr, Victor Sourjik, and Markus Kollmann
"Cellular signaling networks have evolved an astonishing ability to function reliably and with high fidelity in uncertain environments. A crucial prerequisite for the high precision exhibited by many signaling circuits is their ability to keep the concentrations of active signaling compounds within tightly defined bounds, despite strong stochastic fluctuations in copy numbers and other detrimental influences. Based on a simple mathematical formalism, we identify topological organizing principles that facilitate such robust control of intracellular concentrations in the face of multifarious perturbations. Our framework allows us to judge whether a multiple-input-multiple-output reaction network is robust against large perturbations of network parameters and enables the predictive design of perfectly robust synthetic network architectures. Utilizing the Escherichia coli chemotaxis pathway as a hallmark example, we provide experimental evidence that our framework indeed allows us to unravel the topological organization of robust signaling. We demonstrate that the specific organization of the pathway allows the system to maintain global concentration robustness of the diffusible response regulator CheY with respect to several dominant perturbations. Our framework provides a counterpoint to the hypothesis that cellular function relies on an extensive machinery to fine-tune or control intracellular parameters. Rather, we suggest that for a large class of perturbations, there exists an appropriate topology that renders the network output invariant to the respective perturbations." http://1.usa.gov/ILkLXN
"A mathematician from the University of Bristol has teamed up with a biologist from the University of Edinburgh to address a major problem in molecular biology.
Dr Clive Bowsher, Lecturer at the School of Mathematics, and Professor Peter Swain at Synthetic and Systems Biology Edinburgh co-authored a paper in the Proceedings of the National Academy of Sciences showing how to separate ‘signal’ from ‘noise’ when studying the mechanisms of living cells. Cells make decisions in fluctuating environments using inherently noisy biochemical mechanisms. Such effects create considerable, unpredictable variation – known as ‘stochasticity’– both over time and between genetically identical cells. To understand how cells exploit and control these biochemical fluctuations, scientists must identify the sources of stochasticity, quantify their effects, and distinguish variation that carries information about the biological environment from confounding noise...." http://bit.ly/J6yV6I
refers to:
Identifying sources of variation and the flow of information in biochemical networks by Clive G. Bowshera, and Peter S. Swain "To understand how cells control and exploit biochemical fluctuations, we must identify the sources of stochasticity, quantify their effects, and distinguish informative variation from confounding “noise.” We present an analysis that allows fluctuations of biochemical networks to be decomposed into multiple components, gives conditions for the design of experimental reporters to measure all components, and provides a technique to predict the magnitude of these components from models. Further, we identify a particular component of variation that can be used to quantify the efficacy of information flow through a biochemical network. By applying our approach to osmosensing in yeast, we can predict the probability of the different osmotic conditions experienced by wild-type yeast and show that the majority of variation can be informational if we include variation generated in response to the cellular environment. Our results are fundamental to quantifying sources of variation and thus are a means to understand biological “design.”..." http://bit.ly/Kv4TpB
"MIT President Susan Hockfield and Harvard University President Drew Faust, accompanied by top officials from both institutions, announced on Wednesday a new collaboration that will unite the Cambridge-based universities in an ambitious new partnership to deliver online education to learners anywhere in the world.
The new venture, called edX, will provide interactive classes from both Harvard and MIT — for free — to anyone in the world with an Internet connection. But a key goal of the project, Faust said, is “to enhance the educational experience of students who study in our classrooms and laboratories.”..."
"This week sees the online publication of the paper 'Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets' by the Japanese–US team headed by Yoshihiro Kawaoka at the University of Wisconsin-Madison (M. Imai et al. Nature 10.1038/nature10831 (2012). See also pages 7 and 13, and H.-L. Yen and J. S. M. Peiris Nature http://dx.doi.org/10.1038/nature11192; 2012). Kawaoka's paper was one of two submitted last August, reporting mammalian transmissibility of avian flu as a result of artificial genetic manipulation, the principal scientific interest of which arises from the small number of mutations found to be necessary. The other paper, by a team headed by Ron Fouchier at the Erasmus Medical Centre in Rotterdam, the Netherlands, is expected to appear soon in Science....." http://bit.ly/IHaBdE
by Francesca Ceroni, Simone Furini, Alessandra Stefan, Alejandro Hochkoeppler, and Emanuele Giordano "The assembly from modular parts is an efficient approach for creating new devices in Synthetic Biology. In the Bottom-up designing strategy, modular parts are characterized in advance, and then mathematical modelling is used to predict the outcome of the final device. A prerequisite for Bottom-up design is that the biological parts behave in modular way when assembled together. We designed a new synthetic device for post-transcriptional regulation of gene expression, and tested if the outcome of the device can be described from the features of its components. Modular parts showed unpredictable behaviour when assembled in different complex circuits. This prevented a modular description of the device that was possible only under specific conditions. Our findings shed doubts into the feasibility of a pure Bottom-up approach in Synthetic Biology, highlighting the urgency for new strategies for the rational design of synthetic devices."
by Zhang X, Moret BM. "The experimental determination of transcriptional regulatory networks in the laboratory remains difficult and time-consuming, while computational methods to infer these networks provide only modest accuracy. The latter can be attributed partly to the limitations of a single-organism approach. Computational biology has long used comparative and evolutionary approaches to extend the reach and accuracy of its analyses. In this paper, we describe ProPhyC, a probabilistic phylogenetic model and associated inference algorithms, designed to improve the inference of regulatory networks for a family of organisms by using known evolutionary relationships among these organisms. ProPhyC can be used with various network evolutionary models and any existing inference method. Extensive experimental results on both biological and synthetic data confirm that our model (through its associated refinement algorithms) yields substantial improvement in the quality of inferred networks over all current methods. We also compare ProPhyC with a transfer learning approach we design. This approach also uses phylogenetic relationships while inferring regulatory networks for a family of organisms. Using similar input information but designed in a very different framework, this transfer learning approach does not perform better than ProPhyC, which indicates that ProPhyC makes good use of the evolutionary information." http://1.usa.gov/IVIIef
by Evan Mills, Elizabeth Pham, Seema Nagaraj, and Kevin Truong "Mammalian cells re-programmed with engineered transgenes have the potential to be useful therapeutic platforms because they can support large genetic networks, can be taken from a host or patient, and perform useful functions such as migration and secretion. Successful engineering of mammalian cells will require the development of modules that can perform well-defined, reliable functions, such as directed cell migration toward a chemical or physical signal. One inherently modular cellular pathway is the Ca2+ signaling pathway: protein modules that mobilize and respond to Ca2+ are combined across cell types to create complexity. We have designed a chimera of Rac1, a GTPase that controls cell morphology and migration, and calmodulin (CaM), a Ca2+-responsive protein, to control cell migration. The Rac1-CaM chimera (named RACer) controlled lamellipodia growth in response to Ca2+. RACer was combined with LOVS1K (a previously engineered light sensitive Ca2+-mobilizing module) and cytokine receptors to create protein networks where blue light and growth factors regulated cell morphology and thereby, cell migration. To show the generalizability of our design, we created a Cdc42-CaM chimera that controls filopodia growth in response to Ca2+. The insights that have been gained into Ca2+ signaling and cell migration will allow future work to combine engineered protein system to enable re-programmed cell-sensing of relevant therapeutic targets in vivo."
"....H3 Biomedicine integrates human cancer genomics with next-generation synthetic organic chemistry and tumor biology capabilities to generate a large library of novel small-molecule drugs to treat cancer.."
A great tip i just got from +Alejandro Kondrasky on G+ http://www.youtube.com/watch?v=1M26DRlZwSM Looks like an awesome new pdf reader. The video was quite convincing. I like the social option, that users can discuss easily the paper. Moreover, the use of hyperlinked info is great. This is an important example, why we need open source publishing and an open and free hyperlinked internet. I personally do read all journals in a web browser and do not use sandbox apps from the respective publishers in order to support a free internet use. This app is a great step further. The next might be direct dynamic publishing of research data and the semantic web, that means both computer and human readable data submission. This can push apps like this one again one step further. The WikiData project works on this.
Peng Xu, Amerin Vansiri, Namita Bhan, and Mattheos A.G. Koffas
"Harnessing cell factories for producing biofuel and pharmaceutical molecules has stimulated efforts to develop novel synthetic biology tools customized for modular pathway engineering and optimization. Here we report the development of a set of vectors compatible with BioBrickTM standards and its application in metabolic engineering. The engineered ePathBrick vectors comprise four compatible restriction enzyme sites allocated on strategic positions so that different regulatory control signals can be reused and manipulation of expression cassette be streamlined. Specifically, these vectors allow for fine-tuning gene expression by integrating multiple transcriptional activation or repression signals into the operator region. At the same time, ePathBrick vectors support the modular assembly of pathway components and combinatorial generation of pathway diversities with three distinct configurations. We also demonstrated the functionality of a seven gene pathway (~9Kb) assembled on one single ePathBrick vector. The ePathBrick vectors presented here provide a versatile platform for rapid design and optimization of metabolic pathways in E. coli." http://bit.ly/IyKwKY
by Jason W. Chin "The genetic code provides rules by which a genome is decoded to produce proteins of defined amino acid composition and sequence. These rules, which specify 61 codons (triplets of nucleotides) that code for the 20 common amino acids, and 3 codons that signal the termination of protein synthesis, are near-universally conserved in living organisms. Despite conservation of this code and the translational machinery that enforces it, a growing body of work addresses the challenges in reprogramming the genetic code. Designer amino acids, created by synthetic chemistry, can now be incorporated into specific sites in proteins of interest in vitro, in cells, and most recently in a whole animal (see the figure). These routes to unnatural polymer synthesis and evolution are already facilitating the study of cellular processes including protein interactions, protein conformational changes, posttranslational modification biology, and the kinetics of protein transport and cell signaling with a new level of molecular precision (1). Emerging developments may allow the synthesis and evolution of new materials and therapeutics....." http://bit.ly/IycfrM
Kelle A. "The emergence of synthetic biology holds the potential of a major breakthrough in the life sciences by transforming biology into a predictive science. The dual-use characteristics of similar breakthroughs during the twentieth century have led to the application of benignly intended research in e.g. virology, bacteriology and aerobiology in offensive biological weapons programmes. Against this background the article raises the question whether the precautionary governance of synthetic biology can aid in preventing this techno-science witnessing the same fate? In order to address this question, this paper proceeds in four steps: it firstly introduces the emerging techno-science of synthetic biology and presents some of its potential beneficial applications. It secondly analyses contributions to the bioethical discourse on synthetic biology as well as precautionary reasoning and its application to life science research in general and synthetic biology more specifically. The paper then identifies manifestations of a moderate precautionary principle in the emerging synthetic biology dual-use governance discourse. Using a dual-use governance matrix as heuristic device to analyse some of the proposed measures, it concludes that the identified measures can best be described as "patchwork precaution" and that a more systematic approach to construct a web of dual-use precaution for synthetic biology is needed in order to guard more effectively against the field's future misuse for harmful applications."
Jay Keasling talk "The Bold Future of Alternative Energy"
"Nebraska native and synthetic biology pioneer Jay Keasling will deliver "The Bold Future of Alternative Energy" as the final Heuermann Lecture series Tuesday. Keasling, CEO of the Joint BioEnergy Institute in Emeryville, Calif., will speak at 2:30 p.m. in the Hardin Hall Auditorium on the University of Nebraska-Lincoln East Campus. A 2 p.m. reception precedes the lecture. Keasling and colleagues have engineered a strain of E. coli bacteria to produce biodiesel fuel from biomass such as switchgrass without the need of enzyme additives. Now they are seeking ways to make their discovery economically competitive. Keasling is the 2010 recipient of the Presidential Green Chemistry Challenge Award from the U.S. Environmental Protection Agency and numerous other awards. Heuermann lectures focus on providing and sustaining food, natural resources and renewable energy and securing the sustainability of rural communities. For more information, visit http://heuermannlectures.unl.edu." http://bit.ly/J0Wc8p
"Is there a new path to biofuels hiding in a handful of dirt? Lawrence Berkeley National Laboratory (Berkeley Lab) biologist Steve Singer leads a group that wants to find out. They’re exploring whether a common soil bacterium can be engineered to produce liquid transportation fuels much more efficiently than the ways in which advanced biofuels are made today.
The scientists are working with a bacterium called Ralstonia eutropha. It naturally uses hydrogen as an energy source to convert CO2 into various organic compounds.
The group hopes to capitalize on the bacteria’s capabilities and tweak it to produce advanced biofuels that are drop-in replacements for diesel and jet fuel. The process would be powered only by hydrogen and electricity from renewable sources such as solar or wind.
The goal is a biofuel—or electrofuel, as this new approach is called—that doesn’t require photosynthesis...."
Eric Sawyer "A number of months ago I wrote a brief post on artemisinin, often touted as the synthetic biology success story. Here is a much more thoroughly researched take on the topic, including recent news that this "miracle" drug is becoming susceptible to malaria parasite resistance. Artemisia annua, known commonly as sweet wormwood, sweet Annie, and qinghao, is a shrub native to China long used both ornamentally and for medicinal purposes. A. annua is now cultivated globally as the only source of a potent anti-malarial drug, artemisinin. The drug is part of a cocktail of phytochemicals stored in glands on the leaves epidermis ("glandular trichomes,") which are used to deter browsers. Artemisinin has proved effective in the onslaught against the highly adaptable malaria parasite, which has already become resistant to many other drugs....."
Synthetic biology could become the defining technology of the 21st century
Thinking Big: Synthetic Biology - Fidelity Investments Video "Goats are making silk stronger than steel, and we see opportunity. In this video from http://go.fidelity.com/ThinkBig about synthetic biology, Fidelity analyst Robert Chan explains why.
So what is synthetic biology? It's an approach to creating new organisms that fulfill specific functions, using nature as a manufacturing platform and DNA as the raw material. To date, scientists have created goats making spider silk in their milk (it's five times stronger than steel), salmon that grow twice as fast as normal, and bacteria that produce anti-malarial drugs and biodiesel. Each invention could radically increase the supply of these vital products.
As the science evolves -- it is still in a very early, experimental phase -- synthetic biology could become the defining technology of the 21st century, bringing with it new thinking, new questions, and new opportunities.
At Fidelity, we dig deeper into the big issues and hidden trends, using our global reach and expertise to give you smart investing ideas. Put the power of our insights to work for you at http://go.fidelity.com/ThinkBig.
Fidelity Brokerage Services LLC, Member NYSE, SIPC, 900 Salem Street, Smithfield, RI 02917 609830.4.0"http://bit.ly/IuqrX1
"I KNOW IT’S BAD coffee-shop etiquette, but I keep peaking at the laptop computer screen of the young woman beside me. I see long stretches of A’s, T’s, G’s and C’s and a large colorful map of chromosomes. She’s definitely a geneticist.
“Sorry to disturb you,” I say, tilting my own laptop screen towards her, revealing a genome diagram, “but it looks like we’re both working on similar things.” Soon I’m telling her about my postdoctoral research on jellyfish genomes and she’s describing to me her work on salmon genetics. I ask her if she’s a PhD student. She laughs and says, “I’m actually interning as an investment analyst.”
She then explains how a few years ago a friend taught her some basic bioinformatics skills and how to download DNA sequences from the Internet. “Ever since, I’ve been assembling and analyzing genomes in my spare time. I have no formal training in biology, but I’ve learned the basics through a few introductory textbooks that I ordered online. It’s a weird hobby, but a great way to unwind from work and learn about evolution.”..."
"In 1977, a small group of researchers in California changed the world when they wrangled a common gut bacterium into producing a human protein. Using every technique in the book—and inventing some of their own—they scavenged, snipped, and glued together genetic components to synthesize a tiny filament of DNA. They then inserted the new segment into some Escherichia coli cells, tricking them into making the human hormone somatostatin. A year later, these scientists had an E. coli strain that produced insulin, an invaluable drug in the treatment of diabetes. With that, the era of biotechnology was born. A plethora of novel—or at least cheaper—drugs seemed to loom on the horizon. Thirty-odd years on, molecular biologists have delivered on many parts of that early promise, engineering microbes to produce a wide range of pharmaceuticals, including experimental antimalarial medicines and antibiotics. A quick glance in the pantry or storage closet is likely to reveal other products of genetic engineering, too, including foods, food additives and colorings, and even laundry detergent. The list goes on and on. The economic impact of all this has been enormous. Genetic engineering and other forms of biotechnology account for some 40 percent of the recent growth in the U.S. gross domestic product, for example. The biotech sectors in other countries have also made sizable contributions to their economies. And you can expect that trend to continue as genetically engineered organisms tackle even more diverse challenges, such as producing renewable fuels and cleaning up toxic waste. Genetic engineers have indeed accomplished a great deal....." http://bit.ly/IiBksg
"For all its shortcomings, Tentacle Wars is the sort of finger-friendly real-time strategy game that the iPad needs. Based on a two-year-old Flash game, it drafts players into a microscopic war against an alien disease, casting users as the commander of an army of tentacle-covered antibodies.
With taps and swipes you’ll occupy cells by stretching and connecting lengthy tentacles from the antibodies under your control to either enemy cells (who will fight back) or unclaimed territory. Sending out a tentacle to attack uses up resources and weakens the attacking cell, so there’s a constant balance between aggression and patient defense that must be managed in order to overrun and wipe out the disease.
Tentacle Wars is published by FDG, which is doing its best impression of Chillingo: There’s a three-star rating system, the levels are short and divided into themed worlds, and there’s a big page advertising “MORE LEVELS COMING SOON!” If you’ve played any iOS games at all, you know how this works." http://bit.ly/IjSjNt
Master of Science Thesis in the Master Programme of Chemistry and Bioscience
by YUAN YUAN "Green fluorescent protein (GFP) has been broadly used as an efficient reporter system, but not only its stability makes it unsuitable for monitoring transcription dynamics but also the oxygen-demanding chromophore formation restricts its application in aerobic systems. An ubiquitin fusion strategy and an N-degron including a destabilizing N- terminal residue and lysine containing Δk linker can tune the decay rate and provide a range of different stabilities, which is theoretically available for any protein. By N- terminally fusing ubiquitin and N-degron with the GFP-like TurboGFP and a novel flavin mononucleotide (FMN) binding fluorescent protein (FbFP), which works both in aerobic and anaerobic conditions, new destabilized reporter proteins were synthesized and evaluated at transcription level and functional translation level. With methionine, glutamic acid and tyrosine corresponding to relatively strong, middle and weak stability at the conjugate of ubiquitin and Δk linker, TurboGFP and FbFP were integrated into the chromosome of Saccharomyces cerevisiae under control of the inducible GAL1 promoter. The transcription level in each strain was quantified by RT- qPCR and as expected while the functional translation level, i.e. fluorescence intensity was very low. The destabilizing modifications were suspected to affect the fluorescence intensity. Therefore FbFP constructs containing different parts of the modification were developed and proved that the N-terminally fused ubiquitin and linker significantly affected the fluorescence although the mechanisms behind this require further study." http://bit.ly/Klq65P
Jason Silva on singularity, synthetic biology and a desire to transcend human boundaries “That’s what we do with all of our art. A beautiful cathedral, a beautiful painting, a beautiful song—-all of...
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