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Using photosynthesis to generate fresh water

Using photosynthesis to generate fresh water | SynBioFromLeukipposInstitute | Scoop.it
Annegret Honsbein explains how she plans to harness the power of photosynthesis to desalinate sea water and generate fresh water.
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Bio-inspired pneumatic shape-morphing elastomers

Bio-inspired pneumatic shape-morphing elastomers | SynBioFromLeukipposInstitute | Scoop.it
Shape-morphing structures are at the core of future applications in aeronautics1, minimally invasive surgery2, tissue engineering3 and smart materials4. However, current engineering technologies, based on inhomogeneous actuation across the thickness of slender structures, are intrinsically limited to one-directional bending5. Here, we describe a strategy where mesostructured elastomer plates undergo fast, controllable and complex shape transformations under applied pressure. Similar to pioneering techniques based on soft hydrogel swelling6,7,8,9,10, these pneumatic shape-morphing elastomers, termed here as ‘baromorphs’, are inspired by the morphogenesis of biological structures11,12,13,14,15. Geometric restrictions are overcome by controlling precisely the local growth rate and direction through a specific network of airways embedded inside the rubber plate. We show how arbitrary three-dimensional shapes can be programmed using an analytic theoretical model, propose a direct geometric solution to the inverse problem, and illustrate the versatility of the technique with a collection of configurations.
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Analysis of a genetic-metabolic oscillator with piecewise linear models

Interactions between gene regulatory networks and metabolism generate a diversity of dynamics, including multistability and oscillatory behavior. Here, we characterize a regulatory mechanism that drives the emergence of periodic oscillations in metabolic networks subject to genetic feedback regulation by pathway intermediates. We employ a qualitative formalism based on piecewise linear models to systematically analyze the behavior of gene-regulated metabolic pathways. For a pathway with two metabolites and three enzymes, we prove the existence of two co-existing oscillatory behaviors: damped oscillations towards a fixed point or sustained oscillations along a periodic orbit. We show that this mechanism closely resembles the "metabolator", a genetic-metabolic circuit engineered to produce autonomous oscillations in vivo.
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Nucleus Synthetic Biology: Cell Press

We use cookies to help provide and enhance our service and tailor content and ads. By continuing you agree to the use of cookies. Copyright © 2018 Elsevier Inc. except certain content provided by third parties
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Programmed DNA destruction by miniature CRISPR-Cas14 enzymes

CRISPR-Cas9 systems have been causing a revolution in biology. Harrington et al. describe the discovery and technological implementation of an additional type of CRISPR system based on an extracompact effector protein, Cas14. Metagenomics data, particularly from uncultivated samples, uncovered the CRISPR-Cas14 systems containing all the components necessary for adaptive immunity in prokaryotes. At half the size of class 2 CRISPR effectors, Cas14 appears to target single-stranded DNA without class 2 sequence restrictions. By leveraging this activity, a fast and high-fidelity nucleic acid detection system enabled detection of single-nucleotide polymorphisms.
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A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference 

A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference  | SynBioFromLeukipposInstitute | Scoop.it
A central strategy of synthetic biology is to understand the basic processes of living creatures through engineering organisms using the same building blocks. Biological machines described in terms of parts can be studied by computer simulation in any of several languages or robotically assembled in vitro. In this paper we present a language, the Genetic Circuit Description Language (GCDL) and a compiler, the Genetic Circuit Compiler (GCC). This language describes genetic circuits at a level of granularity appropriate both for automated assembly in the laboratory and deriving simulation code. The GCDL follows Semantic Web practice and the compiler makes novel use of the logical inference facilities that are therefore available. We present the GCDL and compiler structure as a study of a tool for generating κ-language simulations from semantic descriptions of genetic circuits.
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Focus on the benefits of building life’s systems from scratch

Focus on the benefits of building life’s systems from scratch | SynBioFromLeukipposInstitute | Scoop.it
Evolution has famously never produced a wheel. Humans famously did — and have spent much of the time since urging each other not to reinvent it. This example illustrates a clear difference between two approaches to problem solving. Nature works with what it has from the bottom up, and eventually finds a solution through an inefficient process of trial and error. Nature has never explicitly asked itself: how can I move this bulk from here to there as quickly and easily as possible? Hence, no wheeled animals, although plenty of legs, wings and other ways of getting about. Humans tend to take the opposite approach: reduce, simplify and break down a complex problem to find the most efficient solution.
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Which biological systems should be engineered?

Which biological systems should be engineered? | SynBioFromLeukipposInstitute | Scoop.it
The difference between tweaking and engineering is subtle but important. Scientists have been tweaking cells at the molecular scale for decades. In 1974, two researchers loaded DNA from a frog into a bacterium, prompting the microbe to produce a foreign RNA1. Twenty years later, scientists used a fluorescent protein from jellyfish to track gene expression in nematode worms, and to tag selected molecules in fruit flies2,3. The fluorescent components lit up under a microscope — kicking off a new era of watching cell biology in action.
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Metabolic Engineering and Synthetic Biology

Metabolic Engineering and Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
In the modern era of next-generation genomics and Fourth Industrial Revolution, there is a growing demand for translational research that brings about not only impactful research but also potential commercialisation of R- and D-based products. Advancement of metabolic engineering and synthetic biology has put forward a viable and innovative biotechnological platform for bioproduct development especially using microbial chassis. In this chapter, readers will be introduced on the concepts of metabolic engineering, synthetic biology and microbial chassis and the applications of these biological engineering (BioE) components in the advancement of industrial and agricultural biotechnology. Main strategies in employing BioE platform are discussed especially for waste bioconversion and value-added product development. More importantly, this chapter will also discuss current endeavours in integrating systems and synthetic biology for microbial production of natural products by introducing flavonoid biosynthesis genes of Polygonum minus, a medicinally important tropical plant in engineered yeast.
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The Future Is Synthetic Biology

Increasingly, synthetic biological systems and molecules are being used to drive biological applications and discovery. At the 2018 Fall Meeting of the American Chemical Society, Cell’s Andrew Rennekamp met up with John Glass, Jim Collins, and Floyd Romesberg to discuss synthetic biology as a discipline and to get their take on where it’s headed. Annotated excerpts from this conversation are presented below, and the full conversation is available with the article online.
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Pre-existing CRISPR immunity found in 96% of humans in study

Pre-existing CRISPR immunity found in 96% of humans in study | SynBioFromLeukipposInstitute | Scoop.it
The happier and healthier future promised by CRISPR-Cas9, the gene-snipping technology that has been heralded as a potential way to treat cancer and other genetic diseases, may take a little longer to achieve. Researchers in Germany found that 96% of the people in their study had a pre-existing immunity to CRISPR.

For the new study, published in the peer-reviewed journal Nature Medicine, researchers took blood samples from 48 healthy volunteers and exposed them to Cas9, the DNA-cutting enzyme derived from Streptococcus pyogenes, which is one of the most commonly used in CRISPR research. As Xconomy first reported, the researchers found that 96% of the people were immune to Cas9, and 85% had antibodies against it.

While being immune to CRISPR sounds bad, CRISPR’s gene editing is typically built on the use of the bacterial protein Cas9. Scientists get the Cas9 from either Staphylococcus aureus, which is either harmless or the cause of staph infections, or from Streptococcus pyogenes, which causes strep throat and can lead to so-called flesh-eating bacteria if it spreads to other parts of the body. So it’s good that your body is immune, even it makes CRISPR’s seeming miracle slightly harder to achieve. For now, scientists are developing work-arounds for those of us with an immunity to CRISPR proteins, including potentially using other enzymes to cut and paste DNA.

This isn’t the first time that scientists have warned about this issue. Back in January, Stanford researchers posted a paper, before it was peer reviewed, noting that the human immune system may be the wrench in the CRISPR works. The research caused the price of CRISPR stocks to tumble, just like when another study was released showing that the DNA editing technique could result in unintended genomic consequences.
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Frontiers | Programming Bacteria with Light - Sensors and Applications in Synthetic Biology 

Photo-receptors are widely present in both prokaryotic and eukaryotic cells, which serves as the foundation of tuning cell behaviors with light. While practices in eukaryotic cells have been relatively established, trials in bacterial cells have only been emerging in the past few years. A number of light sensors have been engineered in bacteria cells and most of them fall into the categories of two-component and one-component systems. Such a sensor toolbox has enabled practices in controlling synthetic circuits at the level of transcription and protein activity which is a major topic in synthetic biology according to the central dogma. Additionally, engineered light sensors and practices of tuning synthetic circuits have served as a foundation for achieving light based real-time feedback control. Here we review programming bacteria cells with light, introducing engineered light sensors in bacteria and their applications, including tuning synthetic circuits and achieving feedback controls over microbial cell culture.
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Programming dynamic control of bacterial gene expression with the chimeric ligand and light-based promoter system

To control cells in a dynamic manner, synthetic biologists require precise control over the threshold levels and timing of gene expression. However, in practice modulating gene expression is widely carried out using prototypical ligand-inducible promoters which have limited tunability and spatiotemporal resolution. Here, we built two dual-input hybrid promoters, each retaining the function of the ligand-inducible promoter while being enhanced with a blue light-switchable tuning knob. Using the new promoters, we show that both ligand and light inputs can be synchronously modulated to achieve desired amplitude or independently regulated to generate desired frequency at a specific amplitude. We exploit the versatile programmability and orthogonality of the two promoters to build the first reprogrammable logic gene circuit, capable of reconfiguring into OR/N-IMPLY logic on the fly in both space and time without the need to modify the circuit. Overall, we demonstrate concentration and time-based combinatorial regulation in live bacterial cells with potential applications in biotechnology and synthetic biology.
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Gene synthesis allows biologists to source genes from farther away in the tree of life

Gene synthesis allows biologists to source genes from farther away in the tree of life | SynBioFromLeukipposInstitute | Scoop.it
Gene synthesis enables creation and modification of genetic sequences at an unprecedented pace, offering enormous potential for new biological functionality but also increasing the need for biosurveillance. In this paper, we introduce a bioinformatics technique for determining whether a gene is natural or synthetic based solely on nucleotide sequence. This technique, grounded in codon theory and machine learning, can correctly classify genes with 97.7% accuracy on a novel data set. We then classify ∼19,000 unique genes from the Addgene non-profit plasmid repository to investigate whether natural and synthetic genes have differential use in heterologous expression. Phylogenetic analysis of distance between source and expression organisms reveals that researchers are using synthesis to source genes from more genetically-distant organisms, particularly for longer genes. We provide empirical evidence that gene synthesis is leading biologists to sample more broadly across the diversity of life, and we provide a foundational tool for the biosurveillance community.
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Selection of Protein-Protein Interactions of Desired Affinities with a Bandpass Circuit

We have developed a genetic circuit in Escherichia coli that can be used to select for protein-protein interactions of different strengths by changing antibiotic concentrations in the media. The genetic circuit links protein-protein interaction strength to β-lactamase activity, while simultaneously imposing tuneable positive and negative selection pressure for β-lactamase activity. Cells only survive if they express interacting proteins with affinities that fall within set high- and low-pass thresholds, i.e. the circuit acts as a bandpass filter for protein-protein interactions. We show that the circuit can be used to recover protein-protein interactions of desired affinity from a mixed population with a range of affinities. The circuit can also be used to select for inhibitors of protein-protein interactions of defined strength.
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Biologists create the most lifelike artificial cells yet

Biologists create the most lifelike artificial cells yet | SynBioFromLeukipposInstitute | Scoop.it
Cell mimics make and pass on proteins that influence their neighbors...
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Models for Cell-free Synthetic Biology: Make Prototyping Easier, Better and Faster

Cell-free TX-TL is an increasingly mature and useful platform for prototyping, testing and engineering biological parts and systems. However, to fully accomplish the promises of synthetic biology, mathematical models are required to facilitate the design and predict the behaviour of biological components in cell-free extracts. We review here the latest models accounting for transcription, translation, competition and depletion of resources as well as genome scale models for lysate-based cell-free TX-TL systems, including their current limitations. These models will have to find ways to account for batch-to-batch variability before being quantitatively predictive in cell-free lysate-based platforms.
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A biomimetic receptor for glucose

A biomimetic receptor for glucose | SynBioFromLeukipposInstitute | Scoop.it
Specific molecular recognition is routine for biology, but has proved difficult to achieve in synthetic systems. Carbohydrate substrates are especially challenging, because of their diversity and similarity to water, the biological solvent. Here we report a synthetic receptor for glucose, which is biomimetic in both design and capabilities. The core structure is simple and symmetrical, yet provides a cavity which almost perfectly complements the all-equatorial β-pyranoside substrate. The receptor’s affinity for glucose, at Ka ~ 18,000 M−1, compares well with natural receptor systems. Selectivities also reach biological levels. Most other saccharides are bound approximately 100 times more weakly, while non-carbohydrate substrates are ignored. Glucose-binding molecules are required for initiatives in diabetes treatment, such as continuous glucose monitoring and glucose-responsive insulin. The performance and tunability of this system augur well for such applications.
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SBOL on the Web: Bringing the Synthetic Biology Open Language to the Web browser 

SBOL on the Web: Bringing the Synthetic Biology Open Language to the Web browser  | SynBioFromLeukipposInstitute | Scoop.it
The Synthetic Biology Open Language (SBOL) is a data standard for the in silico representation of biological designs, such as engineered genetic circuits and their constituent DNA and protein components. The SBOL specification is implemented in the form of software libraries, which can then be used to add SBOL support to both new and existing software tools. Examples of existing SBOL libraries include libSBOLj for Java, libSBOL for C, and pySBOL for Python. These libraries can be used to develop software that runs on a server or is installed locally on a computer. However, currently there are no libraries that can be used to develop SBOL software that runs directly in a Web browser. This omission is notable considering the increasing dominance of JavaScript and the Web as a platform for modern applications. This paper presents sboljs, a JavaScript software library for SBOL that is capable of being used both on the server and in the Web browser.
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How biologists are creating life-like cells from scratch

How biologists are creating life-like cells from scratch | SynBioFromLeukipposInstitute | Scoop.it
Built from the bottom up, synthetic cells and other creations are starting to come together and could soon test the boundaries of life.
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Cell-free transcription–translation: engineering biology from the nanometer to the millimeter scale 

Cell-free transcription–translation (TXTL) has become a highly versatile technology to construct, characterize and interrogate genetically programmed biomolecular systems implemented outside living organisms. By recapitulating gene expression in vitro, TXTL offers unparalleled flexibility to take apart, engineer and analyze quantitatively the effects of chemical, physical and genetic contexts on the function of biochemical systems, from simple regulatory elements to millimeter-scale pattern formation. Here, we review the capabilities of the current cell-free platforms for executing DNA programs in vitro. We describe the recent advances in programming using cell-free expression, a multidisciplinary playground that has enabled a myriad of novel applications in synthetic biology, biotechnology, and biological physics. Finally, we discuss the challenges and perspectives in the research area of TXTL-based constructive biology.
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Programming Morphogenesis through Systems and Synthetic Biology

Programming Morphogenesis through Systems and Synthetic Biology | SynBioFromLeukipposInstitute | Scoop.it
Mammalian tissue development is an intricate, spatiotemporal process of self-organization that emerges from gene regulatory networks of differentiating stem cells. A major goal in stem cell biology is to gain a sufficient understanding of gene regulatory networks and cell–cell interactions to enable the reliable and robust engineering of morphogenesis. Here, we review advances in synthetic biology, single cell genomics, and multiscale modeling, which, when synthesized, provide a framework to achieve the ambitious goal of programming morphogenesis in complex tissues and organoids.
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High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population

High prevalence of Streptococcus pyogenes Cas9-reactive T cells within the adult human population | SynBioFromLeukipposInstitute | Scoop.it
The discovery of the highly efficient site-specific nuclease system CRISPR–Cas9 from Streptococcus pyogenes has galvanized the field of gene therapy1,2. The immunogenicity of Cas9 nuclease has been demonstrated in mice3,4. Preexisting immunity against therapeutic gene vectors or their cargo can decrease the efficacy of a potentially curative treatment and may pose significant safety issues3,4,5,6. S. pyogenes is a common cause for infectious diseases in humans, but it remains unclear whether it induces a T cell memory against the Cas9 nuclease7,8. Here, we show the presence of a preexisting ubiquitous effector T cell response directed toward the most widely used Cas9 homolog from S. pyogenes (SpCas9) within healthy humans. We characterize SpCas9-reactive T cells within the CD4/CD8 compartments for multi-effector potency, cytotoxicity, and lineage determination. In-depth analysis of SpCas9-reactive T cells reveals a high frequency of SpCas9-reactive regulatory T cells that can mitigate SpCas9-reactive effector T cell proliferation and function in vitro. Our results shed light on T cell–mediated immunity toward CRISPR-associated nucleases and offer a possible solution to overcome the problem of preexisting immunity.
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Engineering with Biomolecular Motors

Biomolecular motors, such as the motor protein kinesin, can be used as off-the-shelf components to power hybrid nanosystems. These hybrid systems combine elements from the biological and synthetic toolbox of the nanoengineer and can be used to explore the applications and design principles of active nanosystems. Efforts to advance nanoscale engineering benefit greatly from biological and biophysical research into the operating principles of motor proteins and their biological roles. In return, the process of creating in vitro systems outside of the context of biology can lead to an improved understanding of the physical constraints creating the fitness landscape explored by evolution. However, our main focus is a holistic understanding of the engineering principles applying to systems integrating molecular motors in general. To advance this goal, we and other researchers have designed biomolecular motor-powered nanodevices, which sense, compute, and actuate. In addition to demonstrating that biological solutions can be mimicked in vitro, these devices often demonstrate new paradigms without parallels in current technology. Long-term trends in technology toward the deployment of ever smaller and more numerous motors and computers give us confidence that our work will become increasingly relevant. Here, our discussion aims to step back and look at the big picture. From our perspective, energy efficiency is a key and underappreciated metric in the design of synthetic motors. On the basis of an analogy to ecological principles, we submit that practical molecular motors have to have energy conversion efficiencies of more than 10%, a threshold only exceeded by motor proteins. We also believe that motor and system lifetime is a critical metric and an important topic of investigation. Related questions are if future molecular motors, by necessity, will resemble biomolecular motors in their softness and fragility and have to conform to the "universal performance characteristics of motors", linking the maximum force and mass of any motor, identified by Marden and Allen. The utilization of molecular motors for computing devices emphasizes the interesting relationship among the conversion of energy, extraction of work, and production of information. Our recent work touches upon these topics and discusses molecular clocks as well as a Landauer limit for robotics. What is on the horizon? Just as photovoltaics took advantage of progress in semiconductor fabrication to become commercially viable over a century, one can envision that engineers working with biomolecular motors leverage progress in biotechnology and drug development to create the engines of the future. However, the future source of energy is going to be electricity rather than fossil or biological fuels, a fact that has to be accounted for in our future efforts. In summary, we are convinced that past, ongoing, and future efforts to engineer with biomolecular motors are providing exciting demonstrations and fundamental insights as well as opportunities to wander freely across the borders of engineering, biology, and chemistry.
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Synthetic biology for fundamental biochemical discovery

Synthetic biology for fundamental biochemical discovery | SynBioFromLeukipposInstitute | Scoop.it
Synthetic biologists have developed sophisticated molecular and genetic tools in order to engineer new biochemical functions in cells. Applications for these tools have focused on important problems in energy and medicine, but they can also be applied to address basic science topics that are not easily accessible by classical approaches. We focus on recent work that has utilized synthetic biology approaches – ranging from promoter engineering to the de novo synthesis of cellular parts – to investigate a wide-range of biochemical and cellular questions. Insights obtained by these efforts include how fatty acid composition mediates cellular metabolism, how transcriptional circuits act to stabilize multicellular networks, and fitness trade-offs involved in the selection of genetic regulatory elements. We also highlight common themes about how ‘discovery by synthesis’ approaches can aid fundamental research. For example, re-wiring of native metabolism through metabolic engineering is a powerful tool for investigating biological molecules whose exact composition and abundance is key for function. Meanwhile, endeavors to synthesize cells and their components allow scientists to address evolutionary questions that are otherwise constrained by extant laboratory models.
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Ginkgo Bioworks Is Turning Human Cells Into On-Demand Factories

Ginkgo Bioworks Is Turning Human Cells Into On-Demand Factories | SynBioFromLeukipposInstitute | Scoop.it
The synthetic biology company has opened a new foundry to churn out mammal cells, first for drug development, and later to build potentially anything at all.
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