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Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell

Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell | SynBioFromLeukipposInstitute | Scoop.it
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Lim WA, Lee CM, Tang C.

"A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks."

 http://bit.ly/WM9c7Z

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Programming Morphogenesis through Systems and Synthetic Biology

Stem cell-derived multicellular systems and organoids have opened new opportunities to emulate and understand human development in vitro and provide novel patient specific tissue surrogates for disease modeling.
Single cell sequencing technologies and spatial tissue analysis provide a wealth of information on cellular fate and function and offer invaluable opportunities to decipher developmental processes.
Mammalian synthetic biology utilizes designer synthetic gene circuits to program cell fate and functions towards a desired outcome.
Engineering morphogenesis is an emerging area of science that integrates engineering principles with developmental biology to control and guide collective cell behaviors.
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Microfluidics for the masses | MIT News

Microfluidics for the masses | MIT News | SynBioFromLeukipposInstitute | Scoop.it
A new MIT-designed open-source website might well be the Pinterest of microfluidics. The site, Metafluidics.org, is a free repository of designs for lab-on-a-chip devices, submitted by all sorts of…
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UbiGate: a synthetic biology toolbox to analyse ubiquitination

Ubiquitination is mediated by an enzymatic cascade that results in the modification of substrate proteins, redefining their fate. This post-translational modification is involved in most cellular processes, yet its analysis faces manifold obstacles due to its complex and ubiquitous nature. Reconstitution of the ubiquitination cascade in bacterial systems circumvents several of these problems and was shown to faithfully recapitulate the process.
Here, we present UbiGate − a synthetic biology toolbox, together with an inducible bacterial expression system – to enable the straightforward reconstitution of the ubiquitination cascades of different organisms in Escherichia coli by ‘Golden Gate’ cloning.
This inclusive toolbox uses a hierarchical modular cloning system to assemble complex DNA molecules encoding the multiple genetic elements of the ubiquitination cascade in a predefined order, to generate polycistronic operons for expression.
We demonstrate the efficiency of UbiGate in generating a variety of expression elements to reconstitute autoubiquitination by different E3 ligases and the modification of their substrates, as well as its usefulness for dissecting the process in a time- and cost-effective manner.

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MIT iGEM team uses new CRISPR protein to target cancer-causing RNA splicing errors

MIT iGEM team uses new CRISPR protein to target cancer-causing RNA splicing errors | SynBioFromLeukipposInstitute | Scoop.it
Students built a construct that has the potential to guide a mutated form of Cas13a to a particular mRNA sequence to prevent incorrect RNA splicing. Further testing is necessary, but if successful, this construct could be used therapeutically in small cell lung cancer.
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Scientists shape DNA into doughnuts, teddy bears, and an image of the Mona Lisa

Scientists shape DNA into doughnuts, teddy bears, and an image of the Mona Lisa | SynBioFromLeukipposInstitute | Scoop.it
Scientists have made a big advance in building shapes out of the so-called building blocks of life. New techniques can shape DNA—the double-stranded helical molecule that encodes genes—into objects up to 20 times bigger than previously achieved, three separate groups report today. Together, the new approaches can make objects of virtually any shape: 3D doughnuts and dodecahedrons, cubes with teddy bear–shaped cutouts, and even a tiled image of the Mona Lisa. The techniques could someday lead to a bevy of novel devices for electronics, photonics, nanoscale machines, and possibly disease detection.

Scientists have been making shapes out of DNA since the 1980s, and those efforts took off in 2006 with the invention of a folding technique called DNA origami. It starts with a long DNA strand—called a scaffold—that has a precise sequence of the four molecular units, or nucleotides, dubbed A, C, G, and T, with which DNA spells out its genetic code. Researchers match patches of the scaffold to complementary strands of DNA called staples, which latch on to their targets in two separate places. Connecting those patches forces the scaffold to fold into a prescribed shape. A second version of the technology, introduced in 2012, uses only small strands of DNA—but no scaffolds—that assemble into Lego-like bricks that can then be linked together.

Both approaches have been wildly popular among nanotechnologists, allowing them to design shapes made from DNA from the bottom up. Researchers have also been able to coat their DNA objects with plastics, metals, and other materials to fashion tiny machine components, electronics, and photonic devices. But the size of conventional DNA objects has been limited to about 100 nanometers: Grow them any larger, and they become too floppy to take a particular shape or cannot make enough connections to their neighbors to get bigger. 
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UbiGate: a synthetic biology toolbox to analyse ubiquitination

Ubiquitination is mediated by an enzymatic cascade that results in the modification of substrate proteins, redefining their fate. This post-translational modification is involved in most cellular processes, yet its analysis faces manifold obstacles due to its complex and ubiquitous nature. Reconstitution of the ubiquitination cascade in bacterial systems circumvents several of these problems and was shown to faithfully recapitulate the process. Here, we present UbiGate - a synthetic biology toolbox, together with an inducible bacterial expression system - to enable the straightforward reconstitution of the ubiquitination cascades of different organisms in Escherichia coli by 'Golden Gate' cloning. This inclusive toolbox uses a hierarchical modular cloning system to assemble complex DNA molecules encoding the multiple genetic elements of the ubiquitination cascade in a predefined order, to generate polycistronic operons for expression. We demonstrate the efficiency of UbiGate in generating a variety of expression elements to reconstitute autoubiquitination by different E3 ligases and the modification of their substrates, as well as its usefulness for dissecting the process in a time- and cost-effective manner.
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Mass Spectrometry in Chemical Biology

Mass Spectrometry in Chemical Biology | SynBioFromLeukipposInstitute | Scoop.it
The field of synthetic biology aims to make use of the principles of engineering to understand and re-design biological systems, originating cells/organisms with predictable and novel functions to produce a wide range of chemicals such as fuels, drugs, agrochemicals and polymers. However, advances in the construction of biosynthetic pathways are hampered by bottlenecks such as deficient expression of proteins introduced by the new route, accumulation of toxic intermediates and activation of cell stress responses due to the disturbance caused by the new product. Mass spectrometry helps to elucidate the limitations in synthetic biology. This chapter will present some examples of studies in which mass spectrometry has played a major role, helping synthetic biologists to discover and identify limitations, leading to the optimization of synthetic pathways.
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Bio-computer powered by jellyfish DNA plays Tetris and other retro videogames

Bio-computer powered by jellyfish DNA plays Tetris and other retro videogames | SynBioFromLeukipposInstitute | Scoop.it
An Imperial alumus has developed a bio-pixel display that can play games such as Tetris, Snake or Pong using the protein that makes jellyfish glow

Bixel is a creative, educational tool that helps the public learn about synthetic biology, biotechnology and its applications. It was created by Cell-Free Technology, a start-up co-founded by Dyson School of Design Engineering graduate Helene Steiner.
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Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes

Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes | SynBioFromLeukipposInstitute | Scoop.it
We describe a multiplex genome engineering technology in Saccharomyces cerevisiae based on annealing synthetic oligonucleotides at the lagging strand of DNA replication. The mechanism is independent of Rad51-directed homologous recombination and avoids the creation of double-strand DNA breaks, enabling precise chromosome modifications at single base-pair resolution with an efficiency of >40%, without unintended mutagenic changes at the targeted genetic loci. We observed the simultaneous incorporation of up to 12 oligonucleotides with as many as 60 targeted mutations in one transformation. Iterative transformations of a complex pool of oligonucleotides rapidly produced large combinatorial genomic diversity >105. This method was used to diversify a heterologous β-carotene biosynthetic pathway that produced genetic variants with precise mutations in promoters, genes, and terminators, leading to altered carotenoid levels. Our approach of engineering the conserved processes of DNA replication, repair, and recombination could be automated and establishes a general strategy for multiplex combinatorial genome engineering in eukaryotes.

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Now You Can Genetically Engineer Living Cells with a Home Kit. Should You?

Now You Can Genetically Engineer Living Cells with a Home Kit. Should You? | SynBioFromLeukipposInstitute | Scoop.it
A new kit called Amino promises home-brew bioengineering for less than the price of a MacBook.
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This robot made of algae can swim through your body—thanks to magnets

This robot made of algae can swim through your body—thanks to magnets | SynBioFromLeukipposInstitute | Scoop.it
For decades, engineers have been trying to build medical robots that can deliver drugs or do surgery inside the human body—a somewhat less fantastic version of the 1966 sci-fi film Fantastic Voyage. Now, scientists have manipulated spirulina, a microscopic plant and food supplement, to travel through people in response to magnetic signals. The biohybrid robot could one day carry drugs to specific parts of the body, minimizing side effects. What’s more, the robot—and its magnetic coat—appear to kill cancer cells.

Spirulina, an alga, looks like a tiny coiled spring at the microscopic level. Researchers had been trying, and succeeding to various degrees, to build bots out of rods, tubes, spheres, and even cages no bigger than a cell. Outfitting these tiny devices with an ample power supply has been quite a challenge, as most potential fuels are toxic to humans. Another problem is steering such a microrobot through the body’s maze of proteins and other molecules, which requires both a way to control its movements and to see where it is.

So Li Zhang, a materials scientist at the Chinese University of Hong Kong in Shatin, turned to magnetism—and living organisms. Magnetic fields created outside the body can penetrate living tissue without harm, allowing researchers to move magnetized objects around inside. For maximum mobility, a helical body propelled by twirling works best. Enter spirulina. “It’s surprising that you can find in nature such a convenient structure and that it can behave so nicely,” says Peer Fischer, a physical chemist at the Max Planck Institute for Intelligent Systems in Stuttgart, Germany, who was not involved in the study.
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RNA editing with CRISPR-Cas13

RNA editing with CRISPR-Cas13 | SynBioFromLeukipposInstitute | Scoop.it
Precise transcriptome engineering
Efficient and precise RNA editing to correct disease-relevant transcripts holds great promise for treating genetic disease. Cox et al. took advantage of the ability of Cas13b, an effector from a type VI CRISPR-Cas system, to target specific RNAs directly (see the Perspective by Yang and Chen). They fused Cas13b with the ADAR2 adenosine deaminase domain and used rational protein engineering to improve the resultant enzyme. These approaches yielded an RNA knockdown and editing platform that allowed efficient and specific RNA depletion and correction in mammalian cells.
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Synthetic biology platforms for natural product biosynthesis and disco

Plants are a rich source of unique scaffolds, including 25% of natural-product-derived drugs. However, the discovery, synthesis, and overall material supply chains for sourcing plant natural products and their derivatives remain ad hoc, biased, and tedious. While microbial biosynthesis presents compelling alternatives to traditional approaches based on extraction from natural plant hosts, many challenges exist in the reconstruction of plant specialized metabolic pathways in microbial hosts. My laboratory has developed approaches to address the challenges that arise in the reconstruction of complex biosynthesis schemes, including spatial engineering strategies to direct the activities and specificities of pathway enzymes and recoding strategies to address folding, processing, and stability issues that may arise with the expression of plant enzymes in heterologous microbial hosts. We have utilized these strategies to develop yeast-based production platforms for an important class of plant alkaloids, the benzylisoquinoline alkaloids, including the medicinal opioids. These synthetic biology platforms will lead to transformative advances in natural product discovery, drug development, and production.
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Crispr Therapeutics Plans Its First Clinical Trial for Genetic Disease

Crispr Therapeutics Plans Its First Clinical Trial for Genetic Disease | SynBioFromLeukipposInstitute | Scoop.it
IN LATE 2012, French microbiologist Emmanuelle Charpentier approached a handful of American scientists about starting a company, a Crispr company. They included UC Berkeley’s Jennifer Doudna, George Church at Harvard University, and his former postdoc Feng Zhang of the Broad Institute—the brightest stars in the then-tiny field of Crispr research. Back then barely 100 papers had been published on the little-known guided DNA-cutting system. It certainly hadn’t attracted any money. But Charpentier thought that was about to change, and to simplify the process of intellectual property, she suggested the scientists team up.

It was a noble idea. But it wasn’t to be. Over the next year, as the science got stronger and VCs came sniffing, any hope of unity withered up and washed away, carried on a billion-dollar tide of investment. In the end, Crispr’s leading luminaries formed three companies—Caribou Biosciences, Editas Medicine, and Crispr Therapeutics—to take what they had done in their labs and use it to cure human disease. For nearly five years the “big three’ Crispr biotechs have been promising precise gene therapy solutions to inherited genetic conditions. And now, one of them says it’s ready to test the idea on people.

Last week, Charpentier’s company, Crispr Therapeutics, announced it has asked regulators in Europe for permission to trial a cure for the disease beta thalassemia. The study, testing a genetic tweak to the stem cells that make red blood cells, could begin as soon as next year. The company also plans to file an investigational new drug application with the Food and Drug Administration to treat sickle cell disease in the US within the first few months of 2018. The company, which is co-located in Zug, Switzerland and Cambridge, Massachusetts, said the timing is just a matter of bandwidth, as they file the same data with regulators on two different continents.

Both diseases stem from mutations in a single gene (HBB) that provides instructions for making a protein called beta-globin, a subunit of hemoglobin that binds oxygen and delivers it to tissues throughout the body via red blood cells. One kind of mutation leads to poor production of hemoglobin; another creates abnormal beta-globin structures, causing red blood cells to distort into a crescent or “sickle” shape. Both can cause anemia, repeated infections, and waves of pain. Crispr Therapeutics has developed a way to hit them both with a single treatment.

It works not by targeting HBB, but by boosting expression of a different gene—one that makes fetal hemoglobin. Everyone is born with fetal hemoglobin; it’s how cells transport oxygen between mother and child in the womb. But by six months your body puts the brakes on making fetal hemoglobin and switches over to the adult form. All Crispr Therapeutics’ treatment does is take the brakes off.

From a blood draw, scientists separate out a patient’s hematopoietic stem cells—the ones that make red blood cells. Then, in a petri dish, they zap ‘em with a bit of electricity, allowing the Crispr components to go into the cells and turn on the fetal hemoglobin gene. To make room for the new, edited stem cells, doctors destroy the patient's existing bone marrow cells with radiation or high doses of chemo drugs. Within a week after infusion, the new cells find their way to their home in the bone marrow and start making red blood cells carrying fetal hemoglobin.

According to company data from human cell and animal studies presented at the American Society of Hematology Annual Meeting in Atlanta on Sunday, the treatment results in high editing efficiency, with more than 80 percent of the stem cells carrying at least one edited copy of the gene that turns on fetal hemoglobin production; enough to boost expression levels to 40 percent. Newly minted Crispr Therapeutics CEO Sam Kulkarni says that’s more than enough to ameliorate symptoms and reduce or even eliminate the need for transfusions for beta-thalassemia and sickle cell patients. Previous research has shown that even a small change in the percentage of stem cells that produce healthy red blood cells can have a positive effect on a person with sickle cell diseases.

“I think it’s a momentous occasion for us, but also for the field in general,” says Kulkarni. “Just three years ago we were talking about Crispr-based treatments as sci-fi fantasy, but here we are.”

It was around this time last year that Chinese scientists first used Crispr in humans—to treat an aggressive lung cancer as part of a clinical trial in Chengdu, in Sichuan province. Since then, immunologists at the University of Pennsylvania have begun enrolling terminal cancer patients in the first US Crispr trial—an attempt to turbo-charge T cells so they can better target tumors. But no one has yet used Crispr to fix a genetic disease.
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DNA as a supramolecular building block

DNA as a supramolecular building block | SynBioFromLeukipposInstitute | Scoop.it
PhD student Willem Noteborn has investigated supramolecular structures. These can be useful for the loading of medicines and signalling molecules regarding, for example, cellular differentiation. In his thesis, he describe
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In Vivo Target Gene Activation via CRISPR/Cas9-Mediated Trans-epigenetic Modulation

Current genome-editing systems generally rely on inducing DNA double-strand breaks (DSBs). This may limit their utility in clinical therapies, as unwanted mutations caused by DSBs can have deleterious effects. CRISPR/Cas9 system has recently been repurposed to enable target gene activation, allowing regulation of endogenous gene expression without creating DSBs. However, in vivo implementation of this gain-of-function system has proven difficult. Here, we report a robust system for in vivo activation of endogenous target genes through trans-epigenetic remodeling. The system relies on recruitment of Cas9 and transcriptional activation complexes to target loci by modified single guide RNAs. As proof-of-concept, we used this technology to treat mouse models of diabetes, muscular dystrophy, and acute kidney disease. Results demonstrate that CRISPR/Cas9-mediated target gene activation can be achieved in vivo, leading to measurable phenotypes and amelioration of disease symptoms. This establishes new avenues for developing targeted epigenetic therapies against human diseases.
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CRISPR resources

CRISPR resources | SynBioFromLeukipposInstitute | Scoop.it
Biologists continue to hone their tools for deleting, replacing or otherwise editing DNA and a strategy called CRISPR has become one of the most popular ways to do genome engineering. Utilizing a modified bacterial protein and a RNA that guides it to a specific DNA sequence, the CRISPR system provides unprecedented control over genes in many species, including perhaps humans. This control has allowed many new types of experiments, but also raised questions about what CRISPR can enable.

At least one group has already used CRISPR on human embryos, sparking calls for a moratorium on similar work and an international summit at the end of 2015 to discuss the science and ethics of human gene editing. Meanwhile, CRISPR is making it much easier to generate genetically modified animals and plants, creating new regulatory issues that scientists, agencies politicians and, ultimately, society must address.
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Expansion of the Genetic Alphabet: A Chemist’s Approach to Synthetic Biology

The information available to any organism is encoded in a four nucleotide, two base pair genetic code. Since its earliest days, the field of synthetic biology has endeavored to impart organisms with novel attributes and functions, and perhaps the most fundamental approach to this goal is the creation of a fifth and sixth nucleotide that pair to form a third, unnatural base pair (UBP) and thus allow for the storage and retrieval of increased information. Achieving this goal, by definition, requires synthetic chemistry to create unnatural nucleotides and a medicinal chemistry-like approach to guide their optimization. With this perspective, almost 20 years ago we began designing unnatural nucleotides with the ultimate goal of developing UBPs that function in vivo, and thus serve as the foundation of semi-synthetic organisms (SSOs) capable of storing and retrieving increased information. From the beginning, our efforts focused on the development of nucleotides that bear predominantly hydrophobic nucleobases and thus that pair not based on the complementary hydrogen bonds that are so prominent among the natural base pairs but rather via hydrophobic and packing interactions. It was envisioned that such a pairing mechanism would provide a basal level of selectivity against pairing with natural nucleotides, which we expected would be the greatest challenge; however, this choice mandated starting with analogs that have little or no homology to their natural counterparts and that, perhaps not surprisingly, performed poorly. Progress toward their optimization was driven by the construction of structure–activity relationships, initially from in vitro steady-state kinetic analysis, then later from pre-steady-state and PCR-based assays, and ultimately from performance in vivo, with the results augmented three times with screens that explored combinations of the unnatural nucleotides that were too numerous to fully characterize individually. The structure–activity relationship data identified multiple features required by the UBP, and perhaps most prominent among them was a substituent ortho to the glycosidic linkage that is capable of both hydrophobic packing and hydrogen bonding, and nucleobases that stably stack with flanking natural nucleobases in lieu of the potentially more stabilizing stacking interactions afforded by cross strand intercalation. Most importantly, after the examination of hundreds of unnatural nucleotides and thousands of candidate UBPs, the efforts ultimately resulted in the identification of a family of UBPs that are well recognized by DNA polymerases when incorporated into DNA and that have been used to create SSOs that store and retrieve increased information. In addition to achieving a longstanding goal of synthetic biology, the results have important implications for our understanding of both the molecules and forces that can underlie biological processes, so long considered the purview of molecules benefiting from eons of evolution, and highlight the promise of applying the approaches and methodologies of synthetic and medical chemistry in the pursuit of synthetic biology.
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Synthetic biology-inspired therapies for metabolic diseases


Our ability to engineer mammalian cells with effective therapeutic behaviors has brought new hope for treating metabolic diseases. Synthetic gene networks have been customized to interface with the host metabolism, discriminate between healthy and diseased states, and respond by producing an adjusted dose of the therapeutic molecule. Such devices have the potential to treat a range of dysfunctions that are simply not addressable using conventional therapies. Recently, the repurposing of native signaling pathways has formed the basis of autonomous therapeutic programs genetically installed in mammalian cells and has greatly expanded the possibilities to effectively tackle metabolic disorders. Here, we outline network topologies that have been successfully validated in animal models of metabolic diseases and discuss future developments that will be important for bringing this technology closer to clinical application.
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Expanding DNA's alphabet lets cells produce novel proteins

Expanding DNA's alphabet lets cells produce novel proteins | SynBioFromLeukipposInstitute | Scoop.it
Scientists are expanding the genetic code of life, using man-made DNA to create a semi-synthetic strain of bacteria—and new research shows those altered microbes actually worked to produce proteins unlike those found i
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A cell‐free platform for rapid synthesis and testing of active oligosaccharyltransferases

Protein glycosylation, or the attachment of sugar moieties (glycans) to proteins, is important for protein stability, activity, and immunogenicity. However, understanding the roles and regulations of site-specific glycosylation events remains a significant challenge due to several technological limitations. These limitations include a lack of available tools for biochemical characterization of enzymes involved in glycosylation. A particular challenge is the synthesis of oligosaccharyltransferases (OSTs), which catalyze the attachment of glycans to specific amino acid residues in target proteins. The difficulty arises from the fact that canonical OSTs are large (>70 kDa) and possess multiple transmembrane helices, making them difficult to overexpress in living cells. Here, we address this challenge by establishing a bacterial cell-free protein synthesis platform that enables rapid production of a variety of OSTs in their active conformations. Specifically, by using lipid nanodiscs as cellular membrane mimics, we obtained yields of up to 420 μg/mL for the single-subunit OST enzyme, 'Protein glycosylation B' (PglB) from Campylobacter jejuni, as well as for three additional PglB homologs from Campylobacter coli, Campylobacter lari, and Desulfovibrio gigas. Importantly, all of these enzymes catalyzed N-glycosylation reactions in vitro with no purification or processing needed. Furthermore, we demonstrate the ability of cell-free synthesized OSTs to glycosylate multiple target proteins with varying N-glycosylation acceptor sequons. We anticipate that this broadly applicable production method will advance glycoengineering efforts by enabling preparative expression of membrane-embedded OSTs from all kingdoms of life. This article is protected by copyright. All rights reserved
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Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes

Precise Editing at DNA Replication Forks Enables Multiplex Genome Engineering in Eukaryotes | SynBioFromLeukipposInstitute | Scoop.it
We describe a multiplex genome engineering technology in Saccharomyces cerevisiae based on annealing synthetic oligonucleotides at the lagging strand of DNA replication. The mechanism is independent of Rad51-directed homologous recombination and avoids the creation of double-strand DNA breaks, enabling precise chromosome modifications at single base-pair resolution with an efficiency of >40%, without unintended mutagenic changes at the targeted genetic loci. We observed the simultaneous incorporation of up to 12 oligonucleotides with as many as 60 targeted mutations in one transformation. Iterative transformations of a complex pool of oligonucleotides rapidly produced large combinatorial genomic diversity >105. This method was used to diversify a heterologous β-carotene biosynthetic pathway that produced genetic variants with precise mutations in promoters, genes, and terminators, leading to altered carotenoid levels. Our approach of engineering the conserved processes of DNA replication, repair, and recombination could be automated and establishes a general strategy for multiplex combinatorial genome engineering in eukaryotes.

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Multiplex recording of cellular events over time on CRISPR biological tape

Multiplex recording of cellular events over time on CRISPR biological tape | SynBioFromLeukipposInstitute | Scoop.it
While dynamics underlie many biological processes, our ability to robustly and accurately profile time-varying biological signals and regulatory programs remains limited. Here, we describe a framework to store temporal biological information directly into the genomes of a cell population. A “biological tape recorder” is developed in which biological signals trigger intracellular DNA production that is then recorded by the CRISPR-Cas adaptation system. This approach enables stable recording over multiple days and accurate reconstruction of temporal and lineage information by sequencing CRISPR arrays. We further demonstrate a multiplexing strategy to simultaneously record the temporal availability of three metabolites (copper, trehalose, fucose) in the environment of a cell population over time. This work enables the temporal measurement of dynamic cellular states and environmental changes and suggests new applications for chronicling biological events on a large scale.
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Did a Swedish researcher eat the first CRISPR meal ever served?

Did a Swedish researcher eat the first CRISPR meal ever served? | SynBioFromLeukipposInstitute | Scoop.it
In what Swedish plant scientist Stefan Jansson declares “maybe” a historic event, he cultivated, grew, and ate a plant that had its genome edited with CRISPR-Cas9. Umeå University, where Jansson studies how trees know it’s autumn and how proteins allow plants to harvest light, released a 5 September press release about his meal, a pasta dish that included 300 grams of cabbage he grew from seeds that had been genetically modified with CRISPR-Cas9. The revolutionary technology vastly simplifies the editing of genes, and has triggered many debates about whether its plant products should be considered a genetically modified organism (GMO) and subject to regulation.

As noted by Science Daily and other media outlets, Jansson enjoyed the lunch with Gustaf Klarin, host of a Radio Sweden gardening show, which broadcast it earlier this week (in Swedish). “To our delight—and to some extent to my surprise—the meal turned out really nice,” Jannson wrote in a blog entry on 16 August, the actual day that history might have been made. “Both of us ate with great relish. Gustaf even thought the cabbage was the best tasting vegetable on the plate. And I agreed.”

Jansson’s lab did not create the seed, but he told ScienceInsider he received it from a colleague “in another country” who wants to remain unidentified. As Jansson notes, the European Union has yet to determine whether CRISPR-Cas9 modification that eliminates a gene should be classified as a GMO and thus illegal to grow. But he received approval from the Swedish Board of Agriculture to grow a similar CRISPR-Cas9 seed that his lab had engineered, which the authorities determined was not a GMO as long as it didn’t contain foreign DNA. Jansson told Science that because the plant they ate was by definition not a GMO, “we do of course not need to ask for a permit or even inform them.”
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Webinar | CRISPR unleashed: New tools and applications in live-cell imaging

Webinar | CRISPR unleashed: New tools and applications in live-cell imaging | SynBioFromLeukipposInstitute | Scoop.it
The CRISPR/Cas9 gene editing system has been a boon for researchers, enabling them to manipulate a broad range of genomes quickly and accurately. This novel, versatile tool has been used with great precision for DNA editing as well as a multitude of other applications. Recent enhancements have expanded its abilities; one example is a new, hyperaccurate Cas9 variant that demonstrates high specificity across the genome without compromising on-target activity in human cells. Another is a modification of Cas9 called CRISPRainbow, a system that can more easily label multiple genomic loci in living cells, allowing researchers to better study chromatin dynamics. The unprecedented flexibility of the CRISPR toolset makes it possible to capture imaging phenomena happening at very small scales of space and time. An essential piece of this technology is a camera that captures the fine structure necessary to see the modified DNA (and distinguish it from the background). It must be capable of functioning in challenging environments in living cells, which require cutting-edge light manipulation and detection technologies optimized for light-starved conditions. During this webinar, our experts will examine some of the latest enhancements to the CRISPR/Cas9 system and explain how they are being applied in the lab today.
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