"Amyris, a company that uses synthetic biology to make alternatives to conventional petroleum products, recently decided to wind down its biofuels business and focus on selling higher-value products such as cosmetics. Now it's clear why.
Details about Amyris were disclosed during the company's earnings call last night. They show just how far the company is from making biofuel profitably, and illustrate why the company is getting out of the biofuels business—for now.
Shortly after it was founded, Amyris had set out to make biofuel using genetically modified organisms and simple chemistry to turn sugar into a type of oil that's similar to diesel. It had some success making biodiesel for buses in Brazil. But the chemicals produced by the company's microörganisms can be used for other things as well, such as moisturizers and fragrances, that sell for higher prices.
Last night, the company said the average selling price for all its products is $7.70 per liter, or $29 per gallon, far higher than the price for petroleum-based diesel. (In Brazil, diesel costs about $1 per liter.)....."
Bhartiya D, Kapoor S, Jalali S, Sati S, Kaushik K, Sachidanandan C, Sivasubbu S, Scaria V. "Introduction: Long non-coding RNAs (lncRNAs) are a recently discovered class of non-coding functional RNA which has attracted immense research interest. The growing corpus of literature in the field provides ample evidence to suggest the important role of lncRNAs as regulators in a wide spectrum of biological processes. Recent evidence also suggests the role of lncRNAs in the pathophysiology of disease processes. Areas covered: The authors discuss a conceptual framework for understanding lncRNA-mediated regulation as a function of its interaction with other biomolecules in the cell. They summarize the mechanisms of the known functions of lncRNAs in light of this conceptual framework, and suggest how this insight could help in discovering novel targets for drug discovery. They also argue how certain emerging technologies could be of immense utility, both in discovering potential therapeutic targets as well as in further therapeutic development. Expert opinion: The authors propose how the field could immensely benefit from methodologies and technologies from six emerging fields in molecular and computational biology. They also suggest a futuristic area of lncRNAs design as a potential offshoot of synthetic biology, which would be an attractive field, both for discovery of targets as well as a therapeutic strategy."
Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters
by Blazeck J, Garg R, Reed B, Alper H. "A dynamic range of well-controlled constitutive and tunable promoters are essential for metabolic engineering and synthetic biology applications in all host organisms. Here we apply a synthetic hybrid promoter approach for the creation of strong promoter libraries in the model yeast, Saccharomyces cerevisiae. Synthetic hybrid promoters are composed of two modular components- the enhancer element, consisting of tandem repeats or combinations of upstream activation sequences (UAS), and the core promoter element. We demonstrate the utility of this approach with three main case studies. First, we establish a dynamic range of constitutive promoters and in doing so expand transcriptional capacity of the strongest constitutive yeast promoter, P(GPD) , by 2.5-fold in terms of mRNA levels. Second, we demonstrate the capacity to impart synthetic regulation through a hybrid promoter approach by adding galactose activation and removing glucose repression. Third, we establish a collection of galactose-inducible hybrid promoters that span a nearly 50-fold dynamic range of galactose-induced expression levels and increase the transcriptional capacity of the Gal1 promoter by 15%. These results demonstrate that promoters in S. cerevisiae, and potentially all yeast, are enhancer limited and a synthetic hybrid promoter approach can expand, enhance, and control promoter activity."
"In this paper, I discuss the aetiological account of biological interests, developed by Varner (1998), in the context of artefactual organisms envisioned by current research in synthetic biology. In “Sections 2–5”, I present Varner's theory and criticise it for being incapable of ascribing non-derivative interests to artefactual organisms due to their lack of a history of natural selection. In “Sections 6–7”, I develop a new alternative to Varner's account, building on the organisational theory of biological teleology and function. I argue that the organisational account of biological interest is superior to Varner's aetiological account because it (i) can accommodate both artefactual and naturally evolved organisms, (ii) provides a non-arbitrary and practical way of determining biological interests, (iii) supports the claim that organisms have interests in a sense in which artefacts do not, and (iv) avoids the possibility of there being a conflict between what an organismic part is supposed to do and what is in the interest of the organism."
"Atherosclerosis is intimately coupled to blood flow by the presence of predilection sites. The coupling is through mechanotransduction of endothelial cells and approximately 2000 gene are associated with this process. This paper describes a new platform to study and identify new signalling pathways in endothelial cells covering an atherosclerotic plaque. The identified networks are synthesized in primary cells to study their reaction to flow. This synthetic approach might lead to new insights and drug targets."
"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. In their PNAS paper, Dr Bowsher and Professor Swain show how to decompose the fluctuations of biochemical networks into multiple components and how to design experimental ‘reporters’ to measure these components in living cells..."
referring 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
Harris H Wang, Hwangbeom Kim, Le Cong, Jaehwan Jeong, Duhee Bang & George M Church
"Multiplex automated genome engineering (MAGE) uses short oligonucleotides to scarlessly modify genomes; however, insertions >10 bases are still inefficient but can be improved substantially by selection of highly modified chromosomes. Here we describe 'coselection' MAGE (CoS-MAGE) to optimize biosynthesis of aromatic amino acid derivatives by combinatorially inserting multiple T7 promoters simultaneously into 12 genomic operons. Promoter libraries can be quickly generated to study gain-of-function epistatic interactions in gene networks."
COURSE SUMMARY Synthetic Biology is an emerging technology that hopes to further develop biology as a substrate for engineering by adapting concepts developed in other fields of engineering. Foundational tools to meet this challenge include: ready access to off-the-shelf standardized biological parts and devices; a reliable and defined cellular chassis in which engineers can assemble and power DNA programs; and computational tools as well as measurement standards that enable the ready integration of simpler devices into many-component functional systems. By applying these engineering foundations to the richness and versatility of biology, some of the world’s most significant challenges can be addressed. For example advanced genome, protein and pathway redesign, metabolic engineering and cell-programmed therapeutics have already benefited from the tools of synthetic biology, and these developments will serve as the point of departure for many of the foundational topics. As synthetic biology matures into a robust engineering discipline, it should be capable of transforming the biotechnology, pharmaceutical, and chemical industries as well as suppliers of biotechnology tools, reagents, and services. This summer course offers an unprecedented opportunity to learn about this emerging field from its leaders as well as engage in hands-on computational and laboratory work using the latest tools and techniques. http://bit.ly/J6SgmJ
"As bacteria digest sewage, they also generate electrons. Scientists have tried to harness this phenomenon through microbial fuel cells, in which bacteria generate usable power as they clean wastewater. Now, electro-microbiologist Oriana Bretschger, of the J. Craig Venter Institute, has announced big strides this two-in-one technology. They’ve taken the typical lab prototype and debugged it, scaled it up, and made it cheaper to build.
ORIANA BRETSCHGER (J. Craig Venter Institute):
We’ve moved away from your typical expensive hand-blown laboratory equipment, into something that you could buy from your typical hardware store...."
International workshop highlights opportunities for synthetic biology to improve field based diagnostics. By: Robert Angus May 9, 2012 12:27 PM. An international workshop on 'Novel field based diagnostics' was held at FERA on the 14th ...
Gerald F. Joyce "All known examples of life belong to the same biology, but there is increasing enthusiasm among astronomers, astrobiologists, and synthetic biologists that other forms of life may soon be discovered or synthesized. This enthusiasm should be tempered by the fact that the probability for life to originate is not known. As a guiding principle in parsing potential examples of alternative life, one should ask: How many heritable “bits” of information are involved, and where did they come from? A genetic system that contains more bits than the number that were required to initiate its operation might reasonably be considered a new form of life." http://bit.ly/J8I7H0
"If economic imperatives produce synthetic biology products that are deliberately engineered to fail — as they did with the products of the past — then a future world full of engineered living artefacts (bio-facts) risks being dominated by self-reproducing ‘bio-spam’...."
Novel advances in the design of three-dimensional bio-scaffolds to control cell fate: translation from 2D to 3D
by Santos E, Hernández RM, Pedraz JL, Orive G. "Recreating the most critical aspects of the native extracellular matrix (ECM) is fundamental to understand and control the processes regulating cell fate and cell function. From the ill-defined complexity to the controlled simplicity, we discuss the different strategies that are being carried out by scientists worldwide to achieve the latest advances in the sophistication of three-dimensional (3D) scaffolds, stressing their impact on cell biology, tissue engineering and regenerative medicine. Synthetic and naturally derived polymers like polyethylene glycol, alginate, agarose, etc., together with micro- and nanofabrication techniques are allowing the creation of 3D models where biophysical and biochemical variables can be modified with high precision, orthogonality and even in real-time."
"The translucent bell-shaped figure pumps rhythmically upward through the water, the rise and fall of its body almost identical to that of the moon jelly, Aurelia aurita. The similarity is no coincidence. The figure in the tank is a prototype of an unmanned undersea vehicle designed to run on hydrogen-powered artificial muscles. The wild A. aurita, because of its relatively simple musculature and swimming movements, was the ideal model for Robojelly’s design."
"Protein engineering, chemical biology and synthetic biology would benefit from toolkits of peptide and protein components that can be exchanged reliably between systems whilst maintaining their structural and functional integrity. Ideally, such components should be highly defined and predictable in all respects of sequence, structure, stability, interactions and function. To establish one such toolkit, here we present a Basis Set of de novo designed α-helical coiled-coil peptides that adopt defined and well-characterised parallel dimeric, trimeric and tetrameric states. The designs are based on sequence-to-structure relationships both from the literature and analysis of a database of known coiled-coil X-ray crystal structures. These give foreground sequences to specify the targeted oligomer state. A key feature of the design process is that sequence positions outside of these sites are considered non-essential for structural specificity; as such, they are referred to as the background, are kept non-descript, and are available for mutation as required later. Synthetic peptides were characterized in solution by circular-dichroism spectroscopy and analytical ultracentrifugation, and their structures determined by X-ray crystallography. Intriguingly, a hitherto widely used empirical rule-of-thumb for coiled-coil-dimer specification does not hold in the designed system. However, the desired oligomeric state was achieved by database-informed redesign of that particular foreground, and confirmed experimentally. We envisage that the Basis Set will be of use in directing and controlling protein assembly, with potential applications in chemical and synthetic biology."
"Acetogenic anaerobic bacteria are defined as organisms employing the Wood–Ljungdahl pathway to synthesize acetyl-CoA from CO2 or CO. Their autotrophic mode of metabolism offers the biotechnological chance to combine use of abundantly available substrates with reduction of greenhouse gases. Several companies have already established pilot and demonstration plants for converting waste gases into ethanol, an important biofuel and a natural product of many acetogens. Recombinant DNA approaches now opened the door to construct acetogens, synthesizing important industrial bulk chemicals and biofuels such as acetone and butanol. Thus, novel microbial production platforms are available that no longer compete with nutritional feedstocks."
An introduction to this software can be found here: http://bit.ly/ISK6f0 Solve for X: Omri Amirav-Drory on synthetic life toolkits "Life may be the software that makes its own hardware, but where is the compiler? If we plan to start programming life itself, we are going to need a radically different and better tool kit than the one available to geneticists today. Omri lays out a concrete vision for how such a tool would work and for how it would be used to create the bio-products our future needs so badly."
Nikolai Eroshenko, Sriram Kosuri, Adam H. Marblestone, Nicholas Conway, George M. Church
"De novo synthesis of long double-stranded DNA constructs has a myriad of applications in biology and biological engineering. However, its widespread adoption has been hindered by high costs. Cost can be significantly reduced by using oligonucleotides synthesized on high-density DNA chips. However, most methods for using off-chip DNA for gene synthesis have failed to scale due to the high error rates, low yields, and high chemical complexity of the chip-synthesized oligonucleotides. We have recently demonstrated that some commercial DNA chip manufacturers have improved error rates, and that the issues of chemical complexity and low yields can be solved by using barcoded primers to accurately and efficiently amplify subpools of oligonucleotides. This unit includes protocols for computationally designing the DNA chip, amplifying the oligonucleotide subpools, and assembling 500- to 800-bp constructs. Curr. Protoc. Chem. Biol. 4:1-17"
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