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George Church: "Synthetic Biology could bring extinct species back."

http://www.erderetten.de George Church, Pioneer in Synthetic Biology, Harvard & MIT, USA (c) Brinzanik/Hülswitt/Kreis...
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A global genetic interaction network maps a wiring diagram of cellular function

A global genetic interaction network maps a wiring diagram of cellular function | SynBioFromLeukipposInstitute | Scoop.it
INTRODUCTION
Genetic interactions occur when mutations in two or more genes combine to generate an unexpected phenotype. An extreme negative or synthetic lethal genetic interaction occurs when two mutations, neither lethal individually, combine to cause cell death. Conversely, positive genetic interactions occur when two mutations produce a phenotype that is less severe than expected. Genetic interactions identify functional relationships between genes and can be harnessed for biological discovery and therapeutic target identification. They may also explain a considerable component of the undiscovered genetics associated with human diseases. Here, we describe construction and analysis of a comprehensive genetic interaction network for a eukaryotic cell.
RATIONALE
Genome sequencing projects are providing an unprecedented view of genetic variation. However, our ability to interpret genetic information to predict inherited phenotypes remains limited, in large part due to the extensive buffering of genomes, making most individual eukaryotic genes dispensable for life. To explore the extent to which genetic interactions reveal cellular function and contribute to complex phenotypes, and to discover the general principles of genetic networks, we used automated yeast genetics to construct a global genetic interaction network.
RESULTS
We tested most of the ~6000 genes in the yeast Saccharomyces cerevisiae for all possible pairwise genetic interactions, identifying nearly 1 million interactions, including ~550,000 negative and ~350,000 positive interactions, spanning ~90% of all yeast genes. Essential genes were network hubs, displaying five times as many interactions as nonessential genes. The set of genetic interactions or the genetic interaction profile for a gene provides a quantitative measure of function, and a global network based on genetic interaction profile similarity revealed a hierarchy of modules reflecting the functional architecture of a cell. Negative interactions connected functionally related genes, mapped core bioprocesses, and identified pleiotropic genes, whereas positive interactions often mapped general regulatory connections associated with defects in cell cycle progression or cellular proteostasis. Importantly, the global network illustrates how coherent sets of negative or positive genetic interactions connect protein complex and pathways to map a functional wiring diagram of the cell.
CONCLUSION
A global genetic interaction network highlights the functional organization of a cell and provides a resource for predicting gene and pathway function. This network emphasizes the prevalence of genetic interactions and their potential to compound phenotypes associated with single mutations. Negative genetic interactions tend to connect functionally related genes and thus may be predicted using alternative functional information. Although less functionally informative, positive interactions may provide insights into general mechanisms of genetic suppression or resiliency. We anticipate that the ordered topology of the global genetic network, in which genetic interactions connect coherently within and between protein complexes and pathways, may be exploited to decipher genotype-to-phenotype relationships.

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Synthetic Biology-Based Point-of-Care Diagnostics for Infectious Disease

Infectious diseases outpace all other causes of death in low-income countries, posing global health risks, laying stress on healthcare systems and societies, and taking an avoidable human toll. One solution to this crisis is early diagnosis of infectious disease, which represents a powerful way to optimize treatment, increase patient survival rate, and decrease healthcare costs. However, conventional early diagnosis methods take a long time to generate results, lack accuracy, and are known to seriously underperform with regard to fungal and viral infections. Synthetic biology offers a fast and highly accurate alternative to conventional infectious disease diagnosis. In this review, we outline obstacles to infectious disease diagnostics and discuss two emerging alternatives: synthetic viral diagnostic systems and biosensors. We argue that these synthetic biology-based approaches may overcome diagnostic obstacles in infectious disease and improve health outcomes.
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In a first, 12 Pakistani students set to compete in iGEM world championship 

In a first, 12 Pakistani students set to compete in iGEM world championship  | SynBioFromLeukipposInstitute | Scoop.it
The studen­ts will use synthe­tic biolog­y to solve one of the most pressi­ng enviro­nmenta­l challe­nges facing the countr­y
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Uppsala University iGEM - Timeline 

Uppsala University iGEM, Uppsala (Uppsala, Sweden). 875 likes · 20 talking about this. Synthetic biology is the new revolutionizing field o
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Synthetic biology competition launched

Synthetic biology competition launched | SynBioFromLeukipposInstitute | Scoop.it
An annual competition has been launched to assist companies aiming to solve world issues with synthetic biology.
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Just add water: Biomolecular manufacturing ‘on-the-go’

Wyss Institute team unveils a low-cost, portable method to manufacture biomolecules for a wide range of vaccines, other therapies as well as diagnostics

(BOSTON) — Even amidst all the celebrated advances of modern medicine, basic life-saving interventions are still not reaching massive numbers of people who live in our planet’s most remote and non-industrialized locations. The World Health Organization states that one half of the global population lives in rural areas. And according to UNICEF, last year nearly 20 million infants globally did not receive what we would consider to be basic vaccinations required for a child’s health.

These daunting statistics are largely due to the logistical challenge of transporting vaccines and other biomolecules used in diagnostics and therapy, which conventionally require a "cold chain" of refrigeration from the time of synthesis to the time of administration. In remote areas lacking power or established transport routes, modern medicine often cannot reach those who may need it urgently.
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George Church on the Future of Human Genomics and Synthetic Biology

Filmed April 2016. In his talk “The Future of Human Genomics and Synthetic Biology,” Church discussed the exponentially fast pace of emerging . Georg
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Titanic clash over CRISPR patents turns ugly

Titanic clash over CRISPR patents turns ugly | SynBioFromLeukipposInstitute | Scoop.it
Geneticist George Church has pioneered methods for sequencing and altering genomes. He has been called a founding father of synthetic biology, and is probably the world’s leading authority on efforts to resurrect the extinct woolly mammoth.

Now, a battle over who owns the patent rights to a revolutionary gene-editing technique could hinge, in part, on whether Church’s scientific skill could be considered ‘ordinary’.

Such are the arcane and often bizarre issues the US Patent and Trademark Office (USPTO) must consider in the fight over CRISPR–Cas9 gene editing. But the proceedings, which could drag out for years, have taken an ugly turn from scientific minutiae to accusations of impropriety. “There seem to be a number of allegations of bad actors and bad faith,” says Jacob Sherkow, a legal scholar at New York Law School in New York City. “It’s aggressive.”

CRISPR patent applicants in Europe are also awaiting key rulings — some expected at the end of September — that could decide their fate (see ‘An international conflict’).
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10 TED Talks on technology designed by nature

10 TED Talks on technology designed by nature | SynBioFromLeukipposInstitute | Scoop.it
These exciting innovations and breakthroughs demonstrate what's possible when humans draw inspiration from some of nature’s best work.
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Editorial overview: Synthetic biology - From understanding to engineering biology and back

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The First Synthetic CRISPR RNA Arrayed Library Provides a Drug Discovery Screening Tool for Loss-of-Function Studies

The First Synthetic CRISPR RNA Arrayed Library Provides a Drug Discovery Screening Tool for Loss-of-Function Studies | SynBioFromLeukipposInstitute | Scoop.it
The First Synthetic CRISPR RNA Arrayed Library Provides a Drug Discovery Screening Tool for Loss-of-Function Studies read GE Healthcare news in the SelectScience scientific news archive
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Tools for RNA and cell-free synthetic biology

Tools for RNA and cell-free synthetic biology | SynBioFromLeukipposInstitute | Scoop.it
Amid the myriad recent developments in synthetic biology, progress has been fastest in the areas with the most versatile tools for understanding and engineering biological systems. RNA synthetic biology and synthetic minimal cells are areas where design is limited by the availability of tools to observe, program, and manipulate the systems in question. In this work I present expanded toolsets to achieve these goals. The ability to monitor and perturb RNAs in living cells would benefit greatly from a modular, programmable protein architecture for targeting unmodified RNA sequences. I report that the RNA-binding protein PumHD (Pumilio homology domain), which has been widely used in native and modified form for targeting RNA, can be engineered to yield a set of four canonical protein modules, each of which targets one RNA base. These modules (which I call Pumby, for Pumilio-based assembly) can be concatenated in chains of varying composition and length, to bind desired target RNAs. I validate that the Pumby architecture can perform RNA-directed protein assembly and enhancement of translation of RNAs. I further demonstrate a new use of such RNA-binding proteins, measurement of RNA translation in living cells. Pumby may prove useful for many applications in the measurement, manipulation, and biotechnological utilization of unmodified RNAs in intact cells and systems. Genetic circuits are a fundamental tool in synthetic biology; an open question is how to maximize the modularity of their design, to facilitate their integrity, scalability, and flexibility. Liposome encapsulation enables chemical reactions to proceed in well-isolated environments. I here adapt liposome encapsulation to enable the modular, controlled compartmentalization of genetic circuits and cascades. I demonstrate that it is possible to engineer genetic circuit-containing synthetic minimal cells (synells) so that they contain multiple-part genetic cascades, that these cascades can be controlled by external as well as inter-liposomal communication without cross-talk, and that these cascades can also be fused in a controlled way so that the products of incompatible reactions can be brought together. Synells thus enable more modular creation of synthetic biology cascades, an essential step towards their ultimate programmability.
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New Map Finally Reveals A Global Genetic Network Of Life

New Map Finally Reveals A Global Genetic Network Of Life | SynBioFromLeukipposInstitute | Scoop.it
Researchers at the University of Toronto’s Donnelly Centre have created the first map that shows the global genetic interaction network of a cell. It begins to explain how thousands of genes coordinate with one another to orchestrate cellular life.

The study was led by U of T Professors Brenda Andrews and Charles Boone, and Professor Chad Myers of the University of Minnesota-Twin Cities. It opens the door to a new way of exploring how genes contribute to disease with a potential for developing finely-tuned therapies. The findings are published in the journal Science.



“We’ve created a reference guide for how to chart genetic interactions in a cell,” said Michael Costanzo, a research associate in the Boone lab and one of the researchers who spearheaded the study. “We can now tell what kind of properties to look for in searching for highly connected genes in human genetic networks with the potential to impact genetic diseases.”


The study took 15 years to complete and adds to Andrews’ rich scientific legacy for which she was awarded a Companion of the Order of Canada.

Just as societies in the world are organized from countries down to local communities, the genes in cells operate in hierarchical networks to organize cellular life. Researchers believe that if we are to understand what 20,000 human genes do, we must first find out how they are connected to each other.

Studies in yeast cells first showed the need to look farther than a gene’s individual effect to understand its role. With 6,000 genes, many of which are also found in humans, yeast cells are a relatively simple but powerful stand-ins for human cells.

Over a decade ago, an international consortium of scientists first deleted every yeast gene, one by one. They were surprised to find that only one in five were essential for survival. It wasn’t until last year that advances in gene-editing technology allowed scientists to tackle the equivalent question in human cells. It revealed the same answer: a mere fraction of genes are essential in human cells too.

These findings suggested most genes are “buffered” to protect the cell from mutations and environmental stresses. To understand how this buffering works, scientists had to ask if cells can survive upon losing more than one gene at a time, and they had to test millions of gene pairs.

Andrews, Boone and Myers led the pioneering work in yeast cells by deleting two genes at a time in pair combinations. They were trying to look for gene pairs that are essential for survival. This called for custom-built robots and a state-of-the-art automated pipeline to analyse almost all of the mind-blowing 18 million different combinations.

The yeast map identified genes that work together in a cell. It shows how, if a gene function is lost, there’s another gene in the genome to fill its role. Consider a bicycle analogy: a wheel is akin to an essential gene – without it, you couldn’t ride the bike. But front brakes? Well, as long as the back brakes are working, you might be able to get by. But if you were to lose both sets of brakes, you are heading for trouble.

Geneticists say that front and back brakes are “synthetic lethal,” meaning that losing both – but not one – spells doom. Synthetic lethal gene pairs are relatively rare, but because they tend to control the same process in the cell, they reveal important information about genes we don’t know much about. For example, scientists can predict what an unexplored gene does in the cell simply based on its genetic interaction patterns.

It’s becoming increasingly clear that human genes also have one or more functional backups. So researchers believe that instead of searching for single genes underlying diseases, we should be looking for gene pairs. That is a huge challenge because it means examining about 200 million possible gene pairs in the human genome for association with a disease.

Fortunately, with the know-how from the yeast map, researchers can now begin to map genetic interactions in human cells and even expand it to different cell types. Together with whole-genome sequences and health parameters measured by new personal devices, it should finally become possible to find combinations of genes that underlie human physiology and disease.



“Without our many years of genetic network analysis with yeast, you wouldn’t have known the extent to which genetic interactions drive cellular life or how to begin mapping a global genetic network in human cells,” said Boone, who is also a professor in U of T’s molecular genetics department and a co-director of the Genetic Networks program at the Canadian Institute for Advanced Research (CIFAR) and holds Canada Research Chair in Proteomics, Bioinformatics and Functional Genomics. We have tested the method to completion in a model system to provide the proof of principle for how to approach this problem in human cells. There’s no doubt it will work and generate a wealth of new information."


The concept of synthetic lethality is already changing cancer treatment because of its potential to identify drug targets that exist only in tumour cells. Cancer cells differ from normal cells in that they have scrambled genomes littered with mutations. They’re like a bicycle without a set of brakes. If scientists could find the highly vulnerable back-up genes in cancer, they could target specific drugs at them to destroy only the cells that are sick, leaving the healthy ones untouched.
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Portable, On-Demand Biomolecular Manufacturing

Portable, On-Demand Biomolecular Manufacturing | SynBioFromLeukipposInstitute | Scoop.it
Synthetic biology applies rational design principles of engineering to molecular biology to build genetic devices, which have begun to impact the diagnostic and therapeutic space. This approach has helped to create whole-cell biosensors (Kobayashi et al., 2004), genetically modified probiotics (Danino et al., 2015), and a growing capability for cell-based biomolecular manufacturing. Rooted in genetically engineered production cell lines, biosynthesis is increasingly a mainstay for industrial drug production (Fossati et al., 2014), protein therapeutics (Dimitrov, 2012), fuels (Torella et al., 2015), and other commodities (Chubukov et al., 2016). However, the reliance on living cellular hosts to operate the genetic programs that underpin biosynthesis is accompanied by biosafety regulations, practical hurdles, and specialized skills that limit their operation to laboratory settings. Therefore, vaccines and other protein-based biomolecules must be globally distributed from centralized foundries and, most often, require a cold chain for stability. These limitations impact distribution costs and highlight the challenge of delivering the benefits of these technologies to developing regions. We recently reported a method for the safe deployment of genetically encoded tools (Pardee et al., 2014). Using freeze-dried, cell-free (FD-CF) expression machinery on paper, we generated a platform that retains the fundamental protein synthesis capability of live cells while remaining abiotic, sterile, and portable. In combination with toehold switch RNA sensors (Green et al., 2014), this platform was used to demonstrate a new class of low-cost diagnostic tools (Pardee et al., 2016).

FD-CF reactions offer additional venues for the distributed use of synthetic biology apart from diagnostics, such as the exciting prospect of the portable manufacture of pharmaceuticals, therapeutic proteins, and other biomolecules. In recent years, in vitro biosynthesis from fresh or frozen lysates has developed remarkably, including the biomanufacture of difficult molecules that cause cell toxicity and the incorporation of non-canonical elements (Amiram et al., 2015, Dudley et al., 2015, Karim and Jewett, 2016, Sullivan et al., 2016, Welsh et al., 2012, Zawada et al., 2011). These advances have thus far been tied to laboratory settings where the necessary skills and equipment are found. Building off of this foundation, the proposed use of FD-CF systems, with their long-term activity at room temperature (>1 year) and ease of operation, could alleviate both the restrictions of live-cell biosynthesis and cold-chain distribution requirements (Pardee et al., 2014). Recent reports draw emphasis to a pressing need for the decentralization of therapeutic biomanufacturing, offering novel alternatives that, nonetheless, require expensive, large equipment and highly skilled operators or yet rely on production from living cells (Adamo et al., 2016, Perez-Pinera et al., 2016). Previous work has demonstrated protein production from lyophilized reactions, which strongly supports the notion of advancing this concept further toward on-demand, local biomanufacturing (Salehi et al., 2016, Smith et al., 2014). In addition to portability, the FD-CF format has all of the advantages that are innate to in vitro biosynthesis. Moreover, with buffers, cellular machinery, and molecular instructions all compressed into a single FD reaction pellet, on-demand, on-site activation would only require the addition of water and yields product within 1–2 hr, without the need for specialized equipment and skill. This system could be applied for global health and personalized medicine, making scalable molecular synthesis available to anyone with FD reagents and DNA-encoding biosynthesis instructions.

Here, we present a series of vignettes describing the production of a diverse set of therapeutics and molecular tools for clinical and research environments using FD-CF reaction pellets (Figure 1). Nested within this proof of concept is a drive to create inexpensive alternatives for developing world applications where cost is a major factor to access. We begin with the production of two therapeutic classes of molecules: antimicrobial peptides (AMPs) and vaccines. For the former, we demonstrate purification schemes and validate antimicrobial activity. For the latter, we verify the expression of three vaccine antigens, including the scaled-up production and functional characterization of the diphtheria toxoid antigen (DT), which is administered to an animal model to confirm a successful immune response. Next, we establish a novel combinatorial approach to generate 90 possible affinity conjugates for applications in research and healthcare, of which a subset are functionally validated. Finally, we reconstitute a multi-enzyme biosynthesis pathway for small-molecular therapeutic production and offer a mix-and-match method to synthesize multiple pathway products, which are confirmed using mass spectrometry (MS).
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Portable, On-Demand Biomolecular Manufacturing

Portable, On-Demand Biomolecular Manufacturing | SynBioFromLeukipposInstitute | Scoop.it
Ready-to-use preparations enable on-site, on-demand production of biomolecules like
antimicrobials and vaccines without refrigeration or specialized equipment.
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MIT-Led Team Creates Freeze-Dried Cellular Components to Produce Biopharmaceuticals on Demand

MIT-Led Team Creates Freeze-Dried Cellular Components to Produce Biopharmaceuticals on Demand | SynBioFromLeukipposInstitute | Scoop.it
A team of researchers at MIT and other institutions have developed miniature freeze-dried pellets that possess all of the molecular machinery required to convert DNA into proteins, which could form the basis for on-demand production of vaccines and...
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Synthetic Biology: Innovative approaches for pharmaceutics and drug delivery

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Great Lakes Bioinformatics and the Canadian Computational Biology Collection | PLOS Collections

Great Lakes Bioinformatics and the Canadian Computational Biology Collection | PLOS Collections | SynBioFromLeukipposInstitute | Scoop.it
The first joint Great Lakes Bioinformatics and the Canadian Computational Biology Conference 2016 (GLBIO/CCBC) took place in Toronto from May 16th to 19th. The conference was organized by the Great Lakes Bioinformatics Consortium to provide an interdisciplinary forum for the discussion of research findings and methods. An important goal for the conference was to foster long-term collaborative relationships and networking opportunities within the domain of computational approaches to biology. The conference committee accepted twelve full-length original research papers for oral presentations at the conference, nine of which were then submitted for inclusion in the PLOS Collection devoted to the conference
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Researchers use programmed bacteria as gas sensors to follow microbial communities 

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Cyborg World: How Biohacking Will (and Already Is) Changing Everything

Cyborg World: How Biohacking Will (and Already Is) Changing Everything | SynBioFromLeukipposInstitute | Scoop.it
IN BRIEF

Cyborgs aren't the scary humanoid robots we see in the movies. Through biohacking, one can potentially experience more from life, especially those of us with disabilities.
MODERN CYBORGS

In a presentation titled “Biohacking and the Connected Body” at the Singularity University Global Summit, Hannes Sjoblad, co-founder of the Sweden-based biohacker network Bionyfiken, stated that we likely encounter ‘cyborgs’ on a daily basis without knowing it.

The modern cyborgs we see today include pacemakers, smart insulin monitors, bionic eyes, and robotic arms and legs. These ‘biohacks’ are helping people with disabilities get more from life than ever before. Sjoblad notes this biohacking is utterly reshaping our world, and it will continue to do so. He explains, “we live in a time where, thanks to technology, we can make the deaf hear, the blind see, and the lame walk.”

Indeed, he believes health is where biohacking can help the most. An ingestible smart pill equipped with wireless technology can help monitor the reactions of the body to different medications and treatments—literally telling doctors if the healing process if working from inside the body.

Biohacking can also be beneficial to security. Similar to how we can unlock our smartphones with our fingerprints, imagine the police equipped with guns only they can use. It will eliminate the risk of a bad guy disarming the law enforcers and using the firearm for nefarious purposes.

SIMPLIFYING LIFE

Indeed, biohacking has the power to transform not only our world, but also our bodies. They could be tied directly to everything we do. Including monetary transactions.

Sjoblad demonstrated how biohacking can simplify life through a microchip. Imagine not having to rummage through your bag or search your wallet for your credit card or cash. Simply go to your favorite coffee shop, wave your microchip-equipped hand, and bam! Done. Paid. No threat of being mugged, either. Or imagine having an unfortunate accident and you’re unconscious, but the paramedics have no trouble identifying you because they have emergency access to your basic info.

The Terminator movies have corrupted our minds in terms of how we think about cyborgs. We imagine the rise of traitor robots hell-bent on taking over the world. Truth of the matter is that biohacking has helped improve the quality of human life in many ways.

And if that’s not enough, it is something that you can do yourself.
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Synthetic biology of modular proteins

The evolution of natural modular proteins and domain swapping by protein engineers have shown the disruptive potential of non-homologous recombination to create proteins with novel functions or traits. Bacteriophage endolysins, cellulosomes and polyketide synthases are 3 examples of natural modular proteins with each module having a dedicated function. These modular architectures have been created by extensive duplication, shuffling of domains and insertion/deletion of new domains. Protein engineers mimic these natural processes in vitro to create chimeras with altered properties or novel functions by swapping modules between different parental genes. Most domain swapping efforts are realized with traditional restriction and ligation techniques, which become particularly restrictive when either a large number of variants, or variants of proteins with multiple domains have to be constructed. Recent advances in homology-independent shuffling techniques increasingly address this need, but to realize the full potential of the synthetic biology of modular proteins a complete homology-independent method for both rational and random shuffling of modules from an unlimited number of parental genes is still needed.
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Bioengineered and biohybrid bacteria-based systems for drug delivery

The use of bacterial cells as agents of medical therapy has a long history. Research that was ignited over a century ago with the accidental infection of cancer patients has matured into a platform technology that offers the promise of opening up new potential frontiers in medical treatment. Bacterial cells exhibit unique characteristics that make them well-suited as smart drug delivery agents. Our ability to genetically manipulate the molecular machinery of these cells enables the customization of their therapeutic action as well as its precise tuning and spatio-temporal control, allowing for the design of unique, complex therapeutic functions, unmatched by current drug delivery systems. Early results have been promising, but there are still many important challenges that must be addressed. We present a review of promises and challenges of employing bioengineered bacteria in drug delivery systems and introduce the biohybrid design concept as a new additional paradigm in bacteria-based drug delivery.
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The Role of Synthetic Biology in NASA's Missions

The time has come to for NASA to exploit synthetic biology in pursuit of its missions, including aeronautics, earth science, astrobiology and most notably, human exploration. Conversely, NASA advances the fundamental technology of synthetic biology as no one else can because of its unique expertise in the origin of life and life in extreme environments, including the potential for alternate life forms. This enables unique, creative "game changing" advances. NASA's requirement for minimizing upmass in flight will also drive the field toward miniaturization and automation. These drivers will greatly increase the utility of synthetic biology solutions for military, health in remote areas and commercial purposes. To this end, we have begun a program at NASA to explore the use of synthetic biology in NASA's missions, particular space exploration. As part of this program, we began hosting an iGEM team of undergraduates drawn from Brown and Stanford Universities to conduct synthetic biology research at NASA Ames Research Center. The 2011 team (http://2011.igem.org/Team:Brown-Stanford) produced an award-winning project on using synthetic biology as a basis for a human Mars settlement.
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3rd International Conference on Systems and Synthetic Biology (20 July 2017) 

3rd International Conference on Systems and Synthetic Biology (20 July 2017)  | SynBioFromLeukipposInstitute | Scoop.it
The most comprehensive & up to date source of IoT news
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