SynBioFromLeukipposInstitute

Synthetic Biology is a new open access journal which covers all aspects of synthetic biology; including papers on the mathematical modelling and practical engineering in the field. 

This includes genetic circuit design, computational methods, genetic systems and circuit design, viral engineering, cell design and construction, assembly platforms, DNA synthesis, synthetic metagenomics, pathway construction, gene optimization, protein engineering, metabolic engineering, programmed evolution, cellular manufacturing, mathematical modelling and engineering processes.

The aim of the journal is to provide a forum for original research papers, reviews, commentaries, reports on practical projects, and a venue for in-depth discussion on the topics relevant to synthetic biology.

Metabolic pathways can be engineered to maximize the synthesis of various products of interest. With the advent of computational systems biology, this endeavour is usually carried out through in silico theoretical studies with the aim to guide and complement further in vitro and in vivo experimental efforts. Clearly, what counts is the result in vivo, not only in terms of maximal productivity but also robustness against environmental perturbations. Engineering an organism towards an increased production flux, however, often compromises that robustness. In this contribution, we review and investigate how various analytical approaches used in metabolic engineering and synthetic biology are related to concepts developed by systems and control engineering. While trade-offs between production optimality and cellular robustness have already been studied diagnostically and statically, the dynamics also matter. Integration of the dynamic design aspects of control engineering with the more diagnostic aspects of metabolic, hierarchical control and regulation analysis is leading to the new, conceptual and operational framework required for the design of robust and productive dynamic pathways.

We analyze some of the issues that synthetic biology raises for the social sciences within the “public perceptions of science” framework. The changing roles of public perceptions in policy making are described in relation with changes in the institutional and cultural contexts of science. We take a closer look at the available empirical evidence about public views on synthetic biology against the background of what is known about public perceptions of biotechnology more generally. Many vectors influence public attitudes to biotechnology, notably risk perceptions, tradeoffs between goals and means, ethical views, and trust in science and regulatory institutions. Attitudes are also associated with frames, symbols and worldviews. One of the central worldviews that affects subsets of the life sciences is the current vision of nature: many people are aware of problematic aspects of economic growth that makes intensive use of science and technology, and there is therefore sensitivity to scientific progress that further challenges the boundaries of “natural” processes and objects. Synthetic biology has components in potential conflict with the public’s preference for “naturalness” in many areas, although this is at present dormant due to the low salience of synthetic biology in the media and public.

Synthetic Biology Analysed

Materials scientists would kill to be able to produce a material as amazing as biological muscle, which can retract on command, stretch by about 70% without damage, and heal its own nicks and tears. Now, researchers say they’re getting closer with a synthetic material that can do all these things, though not as well as natural muscle. The advance could one day be useful in robotics and prosthetics.

The concept of an artificial muscle dates back decades. Researchers have proposed numerous different starting materials, from atom-thick tubes of carbon called nanotubes to ceramics to metal alloys. In 2000, scientists showed that some rubberlike polymers called elastomers could be reversibly stretched to up to three times their length by applying a voltage across them. Like almost all synthetic materials, however, these elastomers needed someone to fix them if they were damaged. Working separately, other scientists have used elastomers as the basis for self-healing polymers—materials that can repair tears, seal holes, and even join cut edges. However, most of these have been quite weak and lacked elasticity, making them poor artificial muscles. And nobody has produced an artificial muscle that can repair itself.

Until now, that is. Materials chemist Zhenan Bao of Stanford University in Palo Alto, California, and colleagues unveil today in Nature Chemistry a group of elastomers called Fe-Hpdca-PDMS. The material comprises long, randomly entangled polymer chains containing silicon, oxygen, nitrogen, and carbon atoms mixed with an iron salt. The iron forms chemical bonds with the oxygen and the nitrogen atoms in the polymer, joining the polymer chains both to themselves and to each other, like strings joined with elastic bands at the crossing points. These crosslinks do not prevent the polymer chains from moving altogether, so the material can stretch. But the crosslinks do stop the chains from sliding completely freely. For the material to change shape, the crosslinks have to be stretched, distorted, and sometimes broken and rearranged. When the material is done stretching, the crosslinks return to their original shape, giving the material both strength and elasticity.

Then there’s the self-healing. If you poke a hole in the material, iron atoms on one side of the hole are attracted to oxygen and nitrogen atoms on the other, reforming atomic bonds and closing up the hole within 72 hours. Even when the researchers cut the polymers into two separate pieces, the cut edges ends rejoined almost perfectly if they were placed in contact, recovering almost all of their strength and 90% of their stretchability, even at temperatures as low as -20°C.

When the researchers applied an electric field across the polymers (similar to how muscle tissue is activated), the material’s length increased rapidly by about 2%. When the field was turned off, the material returned to its original size.

One notable weakness of the material is that the change in size after the electric field was applied is still small: Even though the material can normally be stretched up to 45 times its original length and still return to its original shape, its change in size when the field was turned on was much smaller than that of real muscle (which can shorten by up to 40%). This would mean that those robotic legs couldn't bend nearly as well as natural ones.

“In our case, the goal was not to make the best artificial muscle, but rather to develop new materials design rules for stretchable and self-healing materials,” Bao explains. “Artificial muscle is one potential application for our materials.” Bao’s team is now planning further work on increasing the effects of electric fields.

“It's very interesting and extremely elegant work,” says polymer chemist Marek Urban of Clemson University in South Carolina. He says the polymer could eventually be used to make the synthetic muscles needed to move artificial limbs, either to replace missing ones for disabled humans or to allow robots to move things like a human can. He also says the material might have other applications. Materials that expand and contract in response to an electric field are often used as pressure or strain sensors, sometimes self-correcting ones. Self-healing could be useful when sensors have to be placed in extreme conditions such as in space, where repair is sometimes difficult or impossible. "If a material has to be placed in an environment where there's a potential for damage [and] that material self-repairs, that's a huge advantage," Urban says.

Advances in synthetic biology to build microbes with defined and controllable properties are enabling new approaches to design and program multispecies communities. This emerging field of synthetic ecology will be important for many areas of biotechnology, bioenergy and bioremediation. This endeavor draws upon knowledge from synthetic biology, systems biology, microbial ecology and evolution. Fully realizing the potential of this discipline requires the development of new strategies to control the intercellular interactions, spatiotemporal coordination, robustness, stability and biocontainment of synthetic microbial communities. Here, we review recent experimental, analytical and computational advances to study and build multi-species microbial communities with defined functions and behavior for various applications. We also highlight outstanding challenges and future directions to advance this field.

An incisive social commentary masquerading as innocuous entertainment, the 1997 science fiction movie “GATTACA” is alarming in the strength of its rhetoric and in the prescience of its message. It predicts and grapples with bioethical questions that have since surfaced with the invention of new gene-editing and gene-selecting technologies. The film depicts a dystopian society in which mankind has abandoned traditional means of procreation, turning instead to reproductive technologies that allow for the selection or manipulation of genes in order to achieve the most desirable genotypic outcome in offspring. The hero of the story, Vincent Freeman, is born by natural means; the character and the disadvantages he faces as a result of his unconventional birth and lack of hand-picked genetic makeup serve to highlight the flaws in the widespread implementation of such technologies. The advancements in question are depicted as futuristic in the film, but the past few years have seen tremendous progress in the fields of genetics and bioengineering that have brought these technologies to our doorsteps. Enter CRISPR/Cas9.
In layman’s terms, CRISPR/Cas9 is a gene-editing tool that allows for the targeted modification of specific genes. The acronym stands for “clustered regularly-interspaced short palindromic repeats,” and Cas9 is a protein that works in conjunction with CRISPR. The recent advancement of this technology is attributed to Jennifer Doudna of the University of California, Berkeley and to French scientist Emanuelle Charpentier. CRISPR/Cas9 functions by taking advantage of a natural, bacteriophage-fighting mechanism found in bacteria. According to an explanatory video by OriGene Technologies, Inc., CRISPR/Cas9 is an improvement upon previous, similarly oriented technologies in that it is less expensive and more accessible. Another notable characteristic is its accuracy, as it can manipulate specific genes more easily than could the other gene-editing mechanisms.
The possible uses of CRISPR/Cas9 are vast in number and implication. As one of many examples, an article published last year in the American Journal of Bioethics, “Germline Manipulation and our Future Worlds,” lists Mitochondrial Replacement Therapy (MRT) in humans as a possibility of CRISPR/Cas9 implementation. While the list of uses goes on, I wish to draw attention to the ethical implications of the proposed applications of this technology.
Although gene-editing tools have the capacity to facilitate innovations and solutions across a wide range of disciplines, the potential for misuse of CRISPR is enormous. CRISPR poses an unprecedented threat because its lower cost and increased accessibility foreshadows widespread use of the technology to select for desirable traits in children, perhaps even at a consumer level, rather than to select against unhealthy, life-threatening traits or to spur progress in biogenetic research. As the definition of “desirable” traits is relative to culture and era, modifying a germline on the basis of a tenuous definition of what is a “good” trait is a dangerous practice not only for the offspring, but for the greater gene pool. Parallel to the direct biological effects are the social consequences of implementing CRISPR at the layman’s level, as portrayed in “GATTACA.” While CRISPR is more affordable than its predecessors, it is not inexpensive; if the the technology were used on human embryos, the capacity of those with better access and financial capability to hand-pick the genetic makeup of their offspring would exacerbate and cement, at a genetic level, the gaping divide between the wealthy and the underprivileged.
Speculating about the potential for CRISPR to cause irreversible damage to our society and to the human race may seem excessive and reactionary in light of the current state of the technology and the potential it has to do good. To address questions about the status of CRISPR and its implementation, we must reference the decision made by the British HFEA (Human Fertilization and Embryo Authority) in February to allow for the use of CRISPR/Cas9 technology on human embryos for research purposes. The technology and its implementation are moving forward at blinding speed, and it is important to make awareness of the technology widespread. When I questioned him about the impact the recent HFEA decision could have on U.S. policy regarding CRISPR regulation, David Magnus, a renowned bioethicist and professor here at Stanford, notes that many people are concerned about “what this will do in an extremely unregulated environment [referencing reproductive medicine in the U.S.].” He feels that is “probably too early to worry” about the effects of the lack of regulation, but that “there are some pretty wild actors out there” with respect to a possible attempt to implement CRISPR to enhance otherwise normal reproduction; therefore, we should be moving quickly toward clear and all-encompassing regulation. As we push for firmer regulation regarding gene-editing technology, it is important that we temper our message by acknowledging that, if properly and carefully used, CRISPR/Cas9 can catalyze the discovery and invention of many previously elusive, albeit sorely needed, solutions.
 

Prerequisite for any evaluation of synthetic biology is the precise description of its scientific rationale and its biological objects. Here, we develop a layer model that helps to categorize subfields of synthetic biology along their operative procedures and based on the biological status of the organisms generated by synthetic biology. The layer model classifies synthetic and semisynthetic organisms and cells according to their genetic connectivity and to their potential interaction with natural organisms derived by evolution. We use the model to characterize three distinct approaches within synthetic biology: engineering biology, xenobiology and protocell research. While the latter approach generates organisms that hardly could be termed living, xenobiology aims at orthogonal living systems that are disconnected from nature. Synthetic engineering biology could be considered as extreme form of gene technology since all resulting organisms share the universal genetic code with the natural living beings and are based on the same molecular and biochemical principles. Such biological description can be used to determine both the degree of familiarity and the level of uncertainty associated with synthetic organisms and may thus facilitate to judge potential risks of synthetic biology.

In this chapter I analyze the research program of synthetic biology from a conceptual point of view. With this aim, I first highlight four episodes in the history of artificial life research. To give a more abstract characterization of the synthetic aspects of artificial life, I further propose to differentiate between eight categories of artificiality arranged in two broad groups, the first starting from living and the second from non-living precursors. I then discuss artificial systems as models for living systems in general, by pointing out the conceptual affinities in our description of organisms and machines as two types of functional systems that are clearly separated from inorganic bodies. However, despite the fact that living beings are considered as a separate and distinct class, the concept of life is very ambiguous. This is illustrated by giving a list of ontological categories to which the referent of “life” may belong. In conclusion, I discuss whether artificially designed systems can be instantiations of life at all and I point to the influence the potential success of synthetic biology may have on our concept of life by strengthening its individualistic aspects and neglecting, or, for reasons of safety and sustainable use, even intentionally suppressing its evolutionary side. At any rate, the success of synthetic biology will remove one central unifying link of all forms of life on earth at the moment, common descent.

Synthetic biology is a young and heterogeneous field that is constantly on the move. This makes societal evaluation of synthetic biology a challenging task and prone to misunderstandings. Confusions arise not only on the level of what part of synthetic biology the discussion is on, but also on the level of the underlying concepts in use: concepts, for example, of life or artificiality. Instead of directly reviewing the field as a whole, in the first step we therefore focus on characteristic features of synthetic biology that are relevant to the societal discussion. Some of these features apply only to parts of synthetic biology, whereas others might be relevant for synthetic biology as a whole. In the next step we evaluate these new features with respect to the different areas of synthetic biology: do we have the right words and categories to talk about these new features? In the third step we scrutinize traditional concepts like “life” and “artificiality” with regard to their discriminatory power. Lastly, we utilize this refined view for ethical evaluation, risk assessment, analysis of public perception and legal evaluation. This approach will help to differentiate the discussion on synthetic biology. By this we will come to terms with the societal impact of synthetic biology.

Scientists from Imperial have created a new test that could instantly detect the presence of the parasite schistosoma in a water supply.

The test uses a similar technology to a pregnancy test, and changes colour when the parasite is detected.

Details of the technology, which uses genetically modified versions of bacterial cells to detect the parasite, have just been published in the journal Scientific Reports.

We’re at the start of a revolution that will transform our lives as radically as the computer revolution of the 70s. The biological revolution will touch every aspect of our lives: food and health, certainly, but also art, recreation, law, business, and much more.

BioCoder is the newsletter of that revolution. It’s about biology as it moves from research labs into startup incubators, hacker spaces, and even homes. It’s about a very old programming language that we’re just beginning to understand, and that’s written in a code made up of organic chemicals. It’s the product of a sharing community of scientists that stretches from grade school to post docs and university faculty.

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