A logic gate is an idealized or physical device implementing a Boolean function, that performs a logical operation on one or more logic inputs and produces a single logic output. To build a functionally complete logic system, transistors can be used. A single transistor is not a computer, many of them are necessary and they need to communicate with each other, in this way a complex logic system can be created. The architecture of gene regulatory networks is reminiscent of electronic circuits. Modular building blocks that respond in a logical way to one or several inputs are connected to perform a variety of complex tasks. Taking these two main ideas, it could be possible to create a “molecular computer”. Bacillus Booleanus is a project that wants to create a “molecular computer”. How does it work? We are working on the creation of different strains of Bacillus subtilis. Each one of them will be able to perform a single Boolean operation just like a transistor. As we mentioned, our transistors need to communicate, but how could this be possible? In 2011 Ben-Yehuda et. al. identified a type of bacterial communication mediated by nanotubes that bridge neighboring cells, providing a network for exchange of cellular molecules within and between species. By using these nanotubes our bacterium will be capable to communicate with others, creating complex networks of logic gates. Using this, it could be possible to develop a complex network of "transistors" to create, for example, a synthetic metabolic pathway."
Synthetic biology is a new movement setting the hearts and minds of scientists across the world on fire. But really plants, and not scientists, are at the ce...
"As part of our series on synthetic biology, we talk with Kevin Munnelly, CEO of Gen9, a new gene synthesis company founded by George Church of Harvard, Joseph Jacobson of MIT, and Drew Endy of Stanford. According to Munnelly, Gen9 is not just another gene synthesis company, but one which will dramatically disrupt the space. The theory is that just as the declining cost of sequencing has enabled new applications for genomics, so too will a drastically reduced price for synthetic genes. Kevin believes we are just at the beginning of a synthetic biology revolution and it's new technology such as his that will enable it. What are these new applications and why hasn't gene synthesis kept pace with sequencing we ask Kevin in today's show."
"Synthetic biology applies engineering principles to facilitate the predictable design of biological systems. Biological systems composed of modular parts with clearly defined interactions are generally easier to manipulate than complex systems exhibiting a large number of subtle interactions. However, recreating the function of a naturally complex system with simple modular parts can increase fragility. Here, inspired by scaffold-directed signaling in higher organisms, we modularize prokaryotic signal transduction to allow programmable redirection of phosphate flux from a histidine kinase to response regulators based on targeting by eukaryotic protein-protein interaction domains. Although scaffold-directed colocalization alone was sufficient to direct signaling between components, this minimal system suffered from high sensitivity to changing expression levels of each component. To address this fragility, we demonstrate how to engineer autoinhibition into the kinase so that phosphotransfer is possible only upon binding to the scaffold. This system, in which scaffold performs the dual functions of activating this autoinhibited kinase and directing flux to the cotargeted response regulator, was significantly more robust to varying component concentrations. Thus, we demonstrate that design principles inspired by the complex signal-transduction pathways of eukaryotes may be generalized, abstracted, and applied to prokaryotes using well-characterized parts."
Chang, Chieh (San Jose, CA, US) Bharadwaj, Rajiv (Emeryville, CA, US) Singh, Anup K. (Danville, CA, US) Chandrasekaran, Aarthi (San Jose, CA, US) Hillson, Nathan J. (San Francisco, CA, US) "This invention provides methods and compositions for assembling biological constructs (e.g., plasmids, transformed cells, etc.). In certain embodiments the methods involve encapsulating separate components of said biological construct each in a fluid droplet confined in a fluid channel; optionally mixing droplets from different fluid channels to for a sequenced order of droplets carrying different components of said biological construct in a channel or chamber; and optionally combining two or more droplets each containing different components of said biological construct to permit said components to react with each other in one or more reactions contributing to the assembly of said biological construct." http://bit.ly/Tt8Uzp
"Synthetic biology re-imagines existing biological systems by designing and constructing new biological parts, devices, and systems. In the arena of cytoskeleton-based transport, synthetic approaches are currently used in two broad ways. First, molecular motors are harnessed for non-physiological functions in cells. Second, transport systems are engineered in vitro to determine the biophysical rules that govern motility. These rules are then applied to synthetic nanotechnological systems. We review recent advances in both of these areas and conclude by discussing future directions in engineering the cytoskeleton and its motors for transport." http://1.usa.gov/W9HC7q
Denny Luan, a scientist and entrepreneur, explains how the existing process for funding scientific research is limiting and how growing the system will allow...
Carbon nanotubes offer a powerful new way to detect harmful gases in the environment. However, the methods typically used to build carbon nanotube sensors ar...
"The increase in quality, quantity, and complexity of recombinant products relies heavily on the ability to engineer mammalian cell systems. However, the complexity of mammalian cells and lack of synthetic tools to manipulate them impede cell line development processes. Furthermore, the issues of cell productivity, cell stability, cost of goods and services, and speed of development have put new demands on the field. Synthetic biology tools, which have long been applied to microbial cell systems, can improve the speed of R&D and reduce cost of goods. This review highlights recent advances in site-specific genome editing techniques, genetic regulatory elements, and metabolic and pathway engineering of mammalian cell systems that can ultimately facilitate faster and more flexible cell line development.
Highlights ► Demand for speed of development and low cost drive the need for cell line development technologies. ► Advancements in genome targeting enable precise and robust transgene expression and deletions. ► cis-Acting and trans-acting elements enable control of gene expression and complex circuit design. ► These technologies enable more complex metabolic and pathway engineering of mammalian systems. ► Advancements in these areas will drive advances in cell line development."
"A type of stem cell seen as promising for medical therapies is very similar to the type of cells that gives rise to cancer, researchers report.
The findings suggest that although the cells—known as induced pluripotent stem cells (iPSCs)—show substantial potential as a source of replacement cells and tissues to treat injuries, disease, and chronic conditions, scientists and physicians must move cautiously with any clinical use because iPSCs could also cause malignant cancer. “This is the first study that describes the specific molecular pathways that iPSCs and cancer cells share from a direct comparison,” says Paul Knoepfler, associate professor of cell biology and human anatomy at the University of California, Davis, and the study’s principal investigator. “It means that much more study is required before iPSCs can be used clinically. However, our study adds to a growing knowledge base that not only will help make stem cell therapies safer, but also provide us with new understandings about the cancer-causing process and more effective ways to fight the disease.” Since 2007, cell biologists have been able to induce specialized, differentiated cells (such as those obtained from the skin or muscle of a human adult) to become iPSCs. Like embryonic stem cells, iPSCs are a type of stem cell that is able to become any cell type. This “pluripotent” capability means that iPSCs have the potential of being used in treatments for a variety of human diseases, a fundamentally new type of clinical care known as regenerative medicine. iPSCs are considered particularly important because their production avoids the controversy that surrounds embryonic stem cells. In addition, iPSCs can be taken from a patient’s own skin and induced to produce other needed tissues, thereby evading the possibility of immunologic rejection that arises when transplanting cells from a donor to a recipient. In contrast to therapies based on ES cells, iPSCs would eliminate the need for patients to take immunosuppressive drugs. Earlier research indicated that both ES cells and iPSCs pose some health risks. Increasing evidence suggests that pluripotency may be related to rapid cellular growth, a characteristic of cancer. iPSCs, as well as embryonic stem cells, are well known by scientists to have the propensity to cause teratomas, an unusual type of benign tumor that consists of many different cell types. The new study demonstrates for the first time that iPSCs—as well as ES cells—share significant similarities to malignant cancer cells. Findings are reported in the journal Stem Cells and Development.
Unexpectedly similar The investigators compared iPSCs to a form of malignant cancer known as oncogenic foci that are also produced in laboratories; these cell types are used by medical researchers to create models of cancer, particularly sarcoma......"
Gregory Linshiz, Nina Stawski, Sean Poust, Changhao Bi, +Jay Keasling and Nathan J. Hillson
"Labor-intensive multistep biological tasks, such as the construction and cloning of DNA molecules, are prime candidates for laboratory automation. Flexible and biology-friendly operation of robotic equipment is key to its successful integration in biological laboratories, and the efforts required to operate a robot must be much smaller than the alternative manual lab work. To achieve these goals, a simple high-level biology-friendly robot programming language is needed. We have developed and experimentally validated such a language: Programming a Robot (PaR-PaR). The syntax and compiler for the language are based on computer science principles and a deep understanding of biological workflows. PaR-PaR allows researchers to use liquid-handling robots effectively, enabling experiments that would not have been considered previously. After minimal training, a biologist can independently write complicated protocols for a robot within an hour. Adoption of PaR-PaR as a standard cross-platform language would enable hand-written or software-generated robotic protocols to be shared across laboratories...."
St. Louis, MO (Scicasts) – By force of habit we tend to assume computers are made of silicon, but there is actually no necessary connection between the machine and the material.
"As biologists continue the decades-long race to map the genomes of living things, a group of forward-thinking BU engineers is asking the kind of questions that engineers can’t help but ask: what if we built a different genome?
Known as synthetic biologists, they believe that with some skillful genomic tweaks, living organisms, such as cells and microbes, can be put to work doing things that are too dangerous or not even possible for higher life-forms like ourselves.
“There are so many possibilities,” says Douglas Densmore, the Richard and Minda Reidy Family Career Development Assistant Professor in the College of Engineering electrical and computer engineering department. “Some are biotherapeutic. For example, we use chemotherapy to kill cancer cells, which is horribly damaging to the body. We may be able to noninvasively use bacteria that are already in your body to kill cancer cells. Or we can use bacteria to make clean energy.”
In the last few years, as computing power has multiplied and the cost of decoding and synthesizing DNA has nose-dived, synthetic biological possibilities have started to look more like probabilities. Oil spill cleanup is also high on the things-to-do list for customized microbes. So is weapons detection, which may explain why the Office of Naval Research is funding a $7.5 million project called Utilizing Synthetic Biology to Create Programmable Micro-Bio-Robots. The project, which involves Densmore and two other BU engineers as well as researchers from Harvard, MIT, Northeastern, and the University of Pennsylvania, intends to create a dynamic trio of humans, robots, and genetically engineered bacteria, all of which will work together to detect whatever the bacteria are programmed to detect. That could be explosives or toxins or heat or light. The customized bacteria will talk to one another, and they will report to miniature “chaperone robots,” a mere 10 to 100 centimeters long, that will each control thousands of microbes. Finally, the chaperone robots will wirelessly report back to humans. ......." http://bit.ly/WqKa13
Ajai A. Dandekar, Sudha Chugani, E. Peter Greenberg
"The opportunistic pathogen Pseudomonas aeruginosa uses a cell-cell communication system termed “quorum sensing” to control production of public goods, extracellular products that can be used by any community member. Not all individuals respond to quorum-sensing signals and synthesize public goods. Such social cheaters enjoy the benefits of the products secreted by cooperators. There are some P. aeruginosa cellular enzymes controlled by quorum sensing, and we show that quorum sensing–controlled expression of such private goods can put a metabolic constraint on social cheating and prevent a tragedy of the commons. Metabolic constraint of social cheating provides an explanation for private-goods regulation by a cooperative system and has general implications for population biology, infection control, and stabilization of quorum-sensing circuits in synthetic biology."
"Technological advancements in the life sciences are continually pressing forward despite frequent and vocal resistance. Examples of such advancements include reproductive technologies, genetics, stem cell research, nanotechnology, and now synthetic biology. In May 2010, the J. Craig Venter Institute, a multidisciplinary scientific organization led by one of the first scientists to sequence the human genome, announced in the journal Science the creation of the first synthetic cell—a man- made, single-celled organism with the ability to self-replicate. While hailed as a monumental step forward for science, the response from opponents was swift: stop the science from going forward, keep the products off the market, and protect society from the inherent and unknown risks. Recognizing that there are measurable and important differences among advancements in the life sciences in terms of the touchstone risk- benefit dichotomy, this article will examine some promising synthetic biology developments in the medical realm in order to assess the application and performance of the Food and Drug Administration (FDA) regulatory framework. It concludes that the FDA is well equipped to assess and implement protections for products that fit into the traditional clinical trial, review and approval, and post-market regime. However, unlike other developments in the life sciences, synthetic biology poses potential environmental problems not previously contemplated by the limited life-cycle inquiry undertaken by the FDA," free PDF here: http://bit.ly/SXMp9A
"Synthetic biology has historically relied on bacteria as a testing ground for engineering cell behavior through genetic signals. But a small group of researchers have their sights set on redesigning mammalian cells, which have more complex genetic machinery. Daniel Grushkin meets the scientists aiming to reprogram our bodies' cells for a new generation of tailor-made treatments."
"Cyanobacteria and algae are becoming increasingly attractive cell factories for producing renewable biofuels and chemicals due to their ability to capture solar energy and CO(2) and their relatively simple genetic background for genetic manipulation. Increasing research efforts from the synthetic biology approach have been made in recent years to modify cyanobacteria and algae for various biotechnological applications. In this article, we critically review recent progresses in developing genetic tools for characterizing or manipulating cyanobacteria and algae, the applications of genetically modified strains for synthesizing renewable products such as biofuels and chemicals. In addition, the emergent challenges in the development and application of synthetic biology for cyanobacteria and algae are also discussed."
"I’ve been following synthetic biology for the past year or so, and we’re about to see some big changes. Synthetic bio seems to be now where the computer industry was in the late 1970s: still nascent, but about to explode. The hacker culture that drove the development of the personal computer, and that continues to drive technical progress, is forming anew among biohackers.
Computers certainly existed in the ’60s and ’70s, but they were rare, and operated by “professionals” rather than enthusiasts. But an important change took place in the mid-’70s: computing became the domain of amateurs and hobbyists. I read recently that the personal computer revolution started when Steve Wozniak built his own computer in 1975. That’s not quite true, though. Woz was certainly a key player, but he was also part of a club. More important, Silicon Valley’s Homebrew Computer Club wasn’t the only one. At roughly the same time, a friend of mine was building his own computer in a dorm room. And hundreds of people, scattered throughout the U.S. and the rest of the world, were doing the same thing. The revolution wasn’t the result of one person: it was the result of many, all moving in the same direction........."
John W Riggs, Dr. Bonnie Barrilleaux, Natalia Varlakhanova, Kelly Bush, Vanessa Chan, and Dr. Paul Knoepfler
"Induced pluripotent stem cells (iPSC) have the potential for creating patient-specific regenerative medicine therapies, but the links between pluripotency and tumorigenicity raise important safety concerns. More specifically, the methods employed for the production of induced pluripotent stem cells (iPSC) and oncogenic foci (OF), a form of in vitro produced tumor cells, are surprisingly similar, raising potential concerns about iPSC. To test the hypotheses that iPSC and OF are related cell types and, more broadly, that the induction of pluripotency and tumorigenicity are related processes, we produced iPSC and OF in parallel from common parental fibroblasts. When we compared the transcriptomes of these iPSC and OF to their parental fibroblasts, similar transcriptional changes were observed in both iPSC and OF. A significant number of genes repressed during iPSC formation were also repressed in OF, including a large cohort of differentiation-associated genes. iPSC and OF shared a limited number of genes that were upregulated relative to parental fibroblasts but gene ontology analysis pointed toward monosaccharide metabolism as upregulated in both iPSC and OF. iPSC and OF were distinct in that only iPSCs activated a host of pluripotency-related genes, while OF activated cellular damage and specific metabolic pathways. We reprogrammed OF to produce iPSC-like cells, a process dependent on Nanog. However, the reprogrammed OF (ROF) had reduced differentiation potential compared to iPSC, suggesting that oncogenic transformation leads to cellular changes that impair complete reprogramming. Taken together, these findings support a model in which OF and iPSC are related, yet distinct cell types, and in which induced pluripotency and induced tumorigenesis are similar processes." http://bit.ly/QRZU8y
"How cells form global, self-organized structures using genetically encoded molecular rules remains elusive. Here, we take a synthetic biology approach to investigate the design principles governing cell polarization. First, using a coarse-grained computational model, we searched for all possible simple networks that can achieve polarization. All solutions contained one of three minimal motifs: positive feedback, mutual inhibition, or inhibitor with positive feedback. These minimal motifs alone could achieve polarization under limited conditions; circuits that combined two or more of these motifs were significantly more robust. With these design principles as a blueprint, we experimentally constructed artificial polarization networks in yeast, using a toolkit of chimeric signaling proteins that spatially direct the synthesis and degradation of phosphatidylinositol (3,4,5)-trisphosphate (PIP(3)). Circuits with combinatorial motifs yielded clear foci of synthetic PIP(3) that can persist for nearly an hour. Thus, by harnessing localization-regulated signaling molecules, we can engineer simple molecular circuits that reliably execute spatial self-organized programs."
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