SynBioFromLeukipposInstitute
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Synthetic biology - toward therapeutic solutions.

Higher multi-cellular organisms have evolved sophisticated intra- and inter-cellular biological networks that enable cell growth and survival to fulfil an organism's needs. Although such networks allow the assembly of complex tissues and even provide healing and protective capabilities, malfunctioning cells can have severe consequences for an organism's survival. In humans, such events can result in severe disorders and diseases, including metabolic and immunological disorders [1, 2], as well as cancer [3]. Dominating the therapeutic frontier for these potentially lethal disorders, cell and gene therapies aim to relieve or eliminate patient suffering by restoring the function of damaged, diseased, and aging cells and tissues via the introduction of healthy cells or alternative genes. However, despite recent success, these efforts have yet to achieve sufficient therapeutic effects, and further work is needed to ensure the safe and precise control of transgene expression and cellular processes. In this review, we describe the biological tools and devices that are at the forefront of synthetic biology and discuss their potential to advance the specificity, efficiency, and safety of the current generation of cell and gene therapies, including how they can be used to confer curative effects that far surpass those of conventional therapeutics. We also highlight the current therapeutic delivery tools and the current limitations that hamper their use in human applications.
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For Synthetic Biological Circuits, Two Is Better Than One

For Synthetic Biological Circuits, Two Is Better Than One | SynBioFromLeukipposInstitute | Scoop.it
A two-strain microbial circuit can effectively mimic the population-level oscillations of more complex biological systems.
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Complete biosynthesis of opioids in yeast

Opioids are the primary drugs used in Western medicine for pain management and palliative care. Farming of opium poppies remains the sole source of these essential medicines, despite diverse market demands and uncertainty in crop yields due to weather, climate change, and pests. We engineered yeast to produce the selected opioid compounds thebaine and hydrocodone starting from sugar. All work was conducted in a laboratory that is permitted and secured for work with controlled substances. We combined enzyme discovery, enzyme engineering, and pathway and strain optimization to realize full opiate biosynthesis in yeast. The resulting opioid biosynthesis strains required the expression of 21 (thebaine) and 23 (hydrocodone) enzyme activities from plants, mammals, bacteria, and yeast itself. This is a proof of principle, and major hurdles remain before optimization and scale-up could be achieved. Open discussions of options for governing this technology are also needed in order to responsibly realize alternative supplies for these medically relevant compounds.
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The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps

The tiniest Lego: a tale of nanoscale motors, rotors, switches and pumps | SynBioFromLeukipposInstitute | Scoop.it
Inspired by biology, chemists have created a cornucopia of molecular parts that act as switches, motors and ratchets. Now it is time to do something useful with them.
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Chatty cellular machines take synthetic biology to next level

Chatty cellular machines take synthetic biology to next level | SynBioFromLeukipposInstitute | Scoop.it
A new class of multicellular machines that can "talk" to each other will help usher in a new era of smart drugs
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Microfluidics Enables Practical Applications of Genetic Engineering Synthetic Biology Advances

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Designing Life The Ethics of Synthetic Biology, with Professor Drew Endy of Stanford University

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Humans: The Next Platform

Humans: The Next Platform | SynBioFromLeukipposInstitute | Scoop.it
Biohacking and transhumanist advances (including nootropics, extended longevity, cybernetic implants, better behavioral and genetic self-understanding) will materially advance our quality of life and productivity in the coming decade, but we need to be thoughtful about the potential social and ethical pitfalls as we transform. Google Trends shows a marked uptick in searches for “nootropics” and related biohacking fields, so now is the time to have the conversation about the direction we’re headed.

this essay was co-written with Michael Brandt

Digital products and companies are not just changing the way we live our lives, but also playing larger and more influential roles in public policy and governance. This trend of the technology industry driving broader social policy will perhaps be even greater with biohacking companies as their product innovations begin to alter and transform what it means to be human.

An equalizer

Biohacking is simply the next frontier in the drive to better ourselves. People will enhance themselves physically to have better bones, better eyes and better resilience to disease, as well as attain an overall better standard of living. More people will have access to their full potential. However from an ethics perspective, there’s already worrying concerns about the widening socio-economic gap around the world today; there’s an argument that when only the wealthy have access, it further separates the haves from the have-nots.
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Jump-starting life? Fundamental aspects of synthetic biology

What is life and how could it originate? This question lies at the core of understanding the cell as the smallest living unit. Although we are witnessing a golden era of the life sciences, we are ironically still far from giving a convincing answer to this question. In this short article, I argue why synthetic biology in conjunction with the quantitative sciences may provide us with new concepts and tools to address it.

“What is cell biology?” asks the Journal of Cell Biology on the occasion of its 60th anniversary. Raising this simple, yet fundamental question at a time when new data on cells are being collected by the minute is an excellent idea. Information is a necessary, but unfortunately by no means sufficient, requirement for understanding, and the vast amount of data we are now producing may help understand the details but obscure our vision of the cell as a whole. Living systems are inherently complex; this is one of their most distinctive features after billions of years on earth. Complexity is key for their adaptability and resilience, and is both the playground, and the result, of evolution. Unfortunately, the tolerable level of complexity in a connection of thoughts that our brain accepts as an “understanding” is usually rather low, and the most powerful scientific insights, derived by abstraction, have been formulated on the basis of only a few parameters. So either we give up on a systems-level understanding of a cell, and leave it to computers to compile, or we try a theoretical and experimental abstraction of the living cell from its manifold of actual representations. I would like to argue that the latter is possible and will help further our quest to understand the origins of life itself.
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Biohackers: A journey into cyborg America - YouTube

The Verge's Ben Popper explores the world of biohacking, where DIY cyborgs are pushing the bleeding edge of human enhancement. From basement labs to piercing...
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Medical specialists are getting very worried about a gene-editing technology that could create 'designer babies'

Medical specialists are getting very worried about a gene-editing technology that could create 'designer babies' | SynBioFromLeukipposInstitute | Scoop.it
Medical researchers called on Wednesday for detailed, thoughtful debate on future use of new genetic technology that has the potential to create "designer babies".

The technology, called CRISPR-Cas9, allows scientists to edit virtually any gene they target, including in human embryos, enabling them to find and change or replace genetic defects.

Describing CRISPR as "game-changing", the Wellcome Trust global medical charity and four other leading British research organizations urged the scientific community to proceed considerately, allowing time and space for ethical debate.
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Emergent genetic oscillations in a synthetic microbial consortium.

A challenge of synthetic biology is the creation of cooperative microbial systems that exhibit population-level behaviors. Such systems use cellular signaling mechanisms to regulate gene expression across multiple cell types. We describe the construction of a synthetic microbial consortium consisting of two distinct cell types-an "activator" strain and a "repressor" strain. These strains produced two orthogonal cell-signaling molecules that regulate gene expression within a synthetic circuit spanning both strains. The two strains generated emergent, population-level oscillations only when cultured together. Certain network topologies of the two-strain circuit were better at maintaining robust oscillations than others. The ability to program population-level dynamics through the genetic engineering of multiple cooperative strains points the way toward engineering complex synthetic tissues and organs with multiple cell types.
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The Max-Min High-Order Dynamic Bayesian Network for Learning Gene Regulatory Networks with Time-Delayed Regulations.

Accurately reconstructing gene regulatory network (GRN) from gene expression data is a challenging task in systems biology. Although some progresses have been made, the performance of GRN reconstruction still has much room for improvement. Because many regulatory events are asynchronous, learning gene interactions with multiple time delays is an effective way to improve the accuracy of GRN reconstruction. Here we propose a new approach, called Max-Min high-order dynamic Bayesian network (MMHO-DBN) by extending the Max-Min hill-climbing Bayesian network technique originally devised for learning a Bayesian network's structure from static data. Our MMHO-DBN can explicitly model the time lags between regulators and targets in an efficient manner. It first uses constraint-based ideas to limit the space of potential structures, and then applies search-and-score ideas to search for an optimal HO-DBN structure. The performance of MMHO-DBN to GRN reconstruction was evaluated using both synthetic and real gene expression time-series data. Results show that MMHO-DBN is more accurate than current time-delayed GRN learning methods, and has an intermediate computing performance. Furthermore, it is able to learn long time-delayed relationships between genes. We applied sensitivity analysis on our model to study the performance variation along different parameter settings. The result provides hints on the setting of parameters of MMHO-DBN.
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Yeast cell factories on the horizon

For thousands of years, yeast has been used for making beer, bread, and wine. In modern times, it has become a commercial workhorse for producing fuels, chemicals, and pharmaceuticals such as insulin, human serum albumin, and vaccines against hepatitis virus and human papillomavirus. Yeast has also been engineered to make chemicals at industrial scale (e.g., succinic acid, lactic acid, resveratrol) and advanced biofuels (e.g., isobutanol) (1). On page 1095 of this issue, Galanie et al. (2) demonstrate that yeast can now be engineered to produce opioids (2), a major class of compounds used for treating severe pain. Their study represents a tour de force in the metabolic engineering of yeast, as it involved the expression of genes for more than 20 enzymatic activities from plants, mammals, bacteria, and yeast itself. It clearly represents a breakthrough advance for making complex natural products in a controlled and sustainable way.
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Guiding the folding pathway of DNA origami

Guiding the folding pathway of DNA origami | SynBioFromLeukipposInstitute | Scoop.it
DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short ‘staple’ strands1, 2, 3, 4. Its guiding design principle is that the target structure is the single most stable configuration5. The folding transition is cooperative4, 6, 7 and, as in the case of proteins, is governed by information encoded in the polymer sequence8, 9, 10, 11. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield2. Although adjusting assembly conditions2, 12 or following empirical design rules12, 13 can improve yield, well-folded origami often need to be separated from misfolded structures2, 3, 14, 15, 16. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development1, 2, 3, 17, 18, 19 and become a reliable manufacturing technology20.
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BodyHacking Con | 2016

You are a bodyhacker.
Yes, you.
Bodyhackers come in all shapes, sizes, and colors. Even “normal” ones. That’s because bodyhacking isn’t just about appearances. It can relate to inward reflection, chemical adjustment, or even a fancy new watch that connects to a smartphone. The body is a vehicle to be tuned, modified, added to, taken away from, painted, tweaked, and customized. Maybe your preferred method is listed here. Maybe it isn’t. Either way, you belong at BDYHAX
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Gen9 to Collaborate With Non-Profit iGEM on Synthetic Biology Resource - GenomeWeb

Gen9 to Collaborate With Non-Profit iGEM on Synthetic Biology Resource - GenomeWeb | SynBioFromLeukipposInstitute | Scoop.it
Gen9 will make new versions of DNA parts for use by iGEM collaborators, including participants in the non-profit's annual student competition.
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Synthetic Biology A common language makes for a stronger community

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DIY scientists should not trade creativity for funding

DIY scientists should not trade creativity for funding | SynBioFromLeukipposInstitute | Scoop.it
DIY scientists should not trade creativity for funding
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Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters

Cas9-Assisted Targeting of CHromosome segments CATCH enables one-step targeted cloning of large gene clusters | SynBioFromLeukipposInstitute | Scoop.it
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Silk bio-ink could help advance tissue engineering with 3-D printers

Silk bio-ink could help advance tissue engineering with 3-D printers | SynBioFromLeukipposInstitute | Scoop.it
Nanowerk is the leading nanotechnology portal, committed to educate, inform and inspire about nanotechnologies, nanosciences, and other emerging technologies
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GM embryos: time for ethics debate, say scientists

GM embryos: time for ethics debate, say scientists | SynBioFromLeukipposInstitute | Scoop.it
GM embryos: time for ethics debate, say scientists
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Programmable genetic circuits for pathway engineering

Programmable genetic circuits for pathway engineering | SynBioFromLeukipposInstitute | Scoop.it
Gerd Moe-Behrens's insight:

by

Allison Hoynes-O’Connor, Tae Seok Moon 

"Highlights

•Genetic tools from synthetic biology hold potential for pathway engineering.
•With metabolic and environmental sensors, cells can respond to their conditions.
•Genetic circuits connect cellular conditions with the appropriate response.
•Multi-gene targeting allows simultaneous, orthogonal regulation of multiple genes.
•Integration of these three components will lead to advances in pathway engineering."
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