"The latest applications made by engineering living things.
Tom Knight got the bug for bioscience while he was a computer engineer at MIT. He founded the synthetic biology field and help set up bioengineering company Ginkgo BioWorks. He says we’ll soon be able to engineer living things with mechanical precision.Andy Coghlan: How is synthetic biology different from biotechnology?Tom Knight: The main difference is the degree of control. Engineers want their inventions to be as predictable and free from complexity as possible. That's what makes the approach of equipping living things with standardized DNA modules called BioBricks—of which some 15,000 are now available in an open-source registry—different from the prevailing biotechnological practice of inserting single genes randomly into living things. The key realization is that biology is a manufacturing capability. We can have it build the things we want.AC: How do you feel when people call you the "father of synthetic biology"?TK: It's everyone's dream to see ideas that have become popular inspire research projects and students. I've been lucky to see both things happen through the International Genetically Engineered Machines (iGEM) competition for students, which I helped inaugurate in 2004....."
by Nishishita N, Shikamura M, Takenaka C, Takada N, Fusaki N, Kawamata S.
"CD34+ cord blood cells can be reprogrammed effectively on dishes coated with a synthetic RGD motif polymer (PronectinF®) using a temperature sensitive Sendai virus vector (SeV TS7) carrying reprogramming factors OCT3/4, SOX2, KLF4 and c-MYC. Dish-shaped human ES cell-like colonies emerged in serum-free primate ES cell medium (supplemented with bFGF) in 20% O2 culture conditions. The copy numbers of SeV TS7 vectors in the cytoplasm were drastically reduced by a temperature shift at 38°C for three days. Then, single cells from colonies were seeded on PronectinF®-coated 96-well plates and cultured under naïve culture conditions (N2B27-based medium supplemented with LIF, forskolin, a MAPK inhibitor, and a GSK inhibitor in 5% O2) for cloning purpose. Dome-shaped mouse ES cell-like colonies from single cells emerged on PronectinF®-coated dishes. These cells were collected and cultured again in primate ES cell medium supplemented with bFGF in 20% O2 and maintained on PronectinF®-coated dishes. Cells were assessed for reprogramming, including the absence of residual SeV and their potential for three germ layer differentiation. Generation of virus-free induced pluripotent stem cell (iPSC) clones from single cells under feeder-free conditions will solve some of the safety concerns related to use of xeno- or allogeneic-material in culture, and contribute to the characterization and the standardization of iPS cells intended for use in a clinical setting." http://bit.ly/XrSlXh
At December 13th’s SoNYC discussion, our panel will discuss the growth of DIY science, describing some of the opportunities it presents and looking towards the future. The conversation will cover the challenges faced by DIY science enthusiasts, such as safety and accurate data collection, as well as the ways to deal with these concerns within an online world of support. In the build up to this event, we are running a mini-series of guest posts on the SpotOn blog. We will hear from DIY science tinkerers, amateur astronomers, enablers, as well as educators interested in this field. Follow the online chatter using the #DIYSci hashtag and feel free to share your own experiences.http://www.nature.com/spoton/2012/12/spoton-nyc-diy-science-bringing-biotech-home/
"Two major barriers to the advancement of DNA nanotechnology beyond the research lab have been knocked down. This emerging technology employs DNA as a programmable building material for self-assembled, nanometer-scale structures. Many practical applications have been envisioned, and researchers recently demonstrated a synthetic membrane channel made from DNA. Until now, however, design processes were hobbled by a lack of structural feedback. Assembly was slow and often of poor quality...."
"*collaboration will transcend platforms*: It will be increasingly important for any given collaboration package or other app to run on a multitude of platforms – not just one. Taking the easy way out and developing for just one platform will not be acceptable. To be fair though, this multi-platform support imperative extends way beyond BYOD. Like I said in the beginning, 2013 is going to be the year of choice. Whether it’s your phone or the company’s, working from your office or the coffee shop, one option isn’t going to cut it anymore and the companies who can anticipate the next way to use technology smartly and effectively are the ones that will rise to the top this year."
"Synthetic Biology approaches are proposing model systems and providing experimental evidences that life can arise as spontaneous chemical self-assembly process where the ability to reproduce itself is an essential feature of the living system. The appearance of early cells has required an amphiphilic membrane compartment to confine molecular information against diffusion, and the ability to self-replicate the boundary layer and the genetic information. The initial spontaneous self-replication mechanisms based on thermodynamic instability would have evolved in a prebiotic and later biological catalysis. Early studies demonstrate that fatty acids spontaneously assemble into bilayer membranes, building vesicles able to grow by incorporation of free lipid molecules and divide. Early replication mechanisms may have seen inorganic molecules playing a role as the first catalysts. The emergence of a short ribozyme or short catalytic peptide may have initiated the first prebiotic membrane lipid synthesis required for vesicle growth. The evolution of early catalysts towards the simplest translation machine to deliver proteins from RNA sequences was likely to give early birth to one single enzyme controlling protocell membrane division. The cell replication process assisted by complex enzymes for lipid synthesis is the result of evolved pathways in early cells. Evolution from organic molecules to protocells and early cells, thus from chemistry to biology, may have occurred in and out of the boundary layer. Here we review recent experimental work describing membrane and vesicle division mechanisms based on chemico-physical spontaneous processes, inorganic early catalysis and enzyme based mechanisms controlling early protocell division and finally the feedback from minimal genome studies."
"Drug, chemical, and biofuel firms are relying more than ever on artificial fragments of DNA to invent new products. It's called synthetic biology.
For example, teams all over the world are now in their labs looking to create novel biotech compounds or drugs by inserting synthetic DNA into cells, either living or artificial. They're also growing new microorganisms that yield biofuels to be used in lieu of oil. Trouble is, the process is so complex that it can take days to synthesize these man-made genes, usually in small batches. Not only is it time consuming, but it requires the use of costly robots and other advanced gear. Simply stated, if someone came along with a breakthrough that greatly speeded up the development of synthetic genes, it could affect several industries at once, not to mention its own value in the market. Allow me to introduce you to Gen9 Inc. The company is blazing a trail in the development of scalable technologies for synthesizing genes. Now, Gen9 is a small, new dynamic company. And its potential is huge. It was formed last summer around a unique new device that greatly speeds up the process of creating synthetic DNA. Even better, it cuts the cost of that process by leaps and bounds. A Huge Breakthrough in Synthetic Biology The system this company created is known as BioFab. This system can quickly and cheaply produce tens of thousands of double-stranded DNA fragments. Talk about economies of scale -- it's this bulk processing that gives Gen9 such a huge advantage over other firms. It works like this: BioFab can produce tens of thousands of double-stranded DNA fragments that are between 500 and 1,000 base pairs in length. Gen9 says it can produce the synthetic DNA for less than 10 cents per base pair, which the company says is as little as 20% the cost of other firms. No wonder the small company is attracting so much buzz from scientists and professional investors. ...."
Sean Ward is the co-founder and CEO of Synthace, an applied synthetic biology spinout from UCL. His talks gives a flavor of how university research and colla...
Gerd Moe-Behrens's insight:
- a synthetic biology startup,
by Sean Ward
"Sean Ward is the co-founder and CEO of Synthace, an applied synthetic biology spinout from UCL. His talks gives a flavor of how university research and collaboration can be turned into products. With the recent advent of the iGEM entrepreneurial competition and a surge in investment, the time to progress synthetic biology commercially has never been better.
by Alessandro Porchetta , Alexis Vallée-Bélisle , Kevin W. Plaxco , and Francesco Ricci
"Here we demonstrate multiple, complementary approaches by which to tune, extend or narrow the dynamic range of aptamer-based sensors. Specifically, we have employed both distal site mutations and allosteric control to tune the affinity and dynamic range of a fluorescent aptamer beacon. We show that allosteric control, achieved by using a set of easily designed oligonucleotide inhibitors that competes against the folding of the aptamer, allows to rationally and finely tune the affinity of our model aptamer across three orders of magnitude of target concentration with greater precision than that achieved using mutational approaches. Using these methods we generate sets of aptamers varying significantly in target affinity, which we then combined to recreate several of the mechanisms employed by nature to both narrow and broaden the dynamic range of biological receptors. Such ability to finely control the affinity and dynamic range of aptamers may find many applications in synthetic biology, drug delivery and targeted therapies, fields in which aptamers are of rapidly growing importance." http://bit.ly/SUVDng
by Shiping Song, Lihua Wang, Jiang Li, Jianlong Zhao, Chunhai Fan
"Nucleic-acid aptamers have attracted intense interest and found wide app- lications in a range of areas. In this review, we summarize recent advances in the development of aptamer-based biosensors and bioassay methods, most of which have employed electrochemical, optical and mass-sensitive analytical techniques. Aptamers exhibit many advantages as recognition elements in biosensing when compared to traditional antibodies. They are small in size, chemically stable and cost effective. More importantly, aptamers offer re- markable flexibility and convenience in the design of their structures, which has led to novel biosensors that have exhibited high sensitivity and selecti- vity. Recently, the combination of aptamers with novel nanomaterials has significantly improved the performance of aptamer-based sensors, which we also review in this article. In view of the unprecedented advantages brought by aptamers, we expect aptamer-based biosensors to find broad applications in biomedical diagnostics, environmental monitoring and homeland security."
"We discuss how statistical inference techniques can be applied in the context of designing novel biological systems. Bayesian techniques have found widespread application and acceptance in the systems biology community, where they are used for both parameter estimation and model selection. Here we show that the same approaches can also be used in order to engineer synthetic biological systems by inferring the structure and parameters that are most likely to give rise to the dynamics that we require a system to exhibit. Problems that are shared between applications in systems and synthetic biology include the vast potential spaces that need to be searched for suitable models and model parameters; the complex forms of likelihood functions; and the interplay between noise at the molecular level and nonlinearity in the dynamics owing to often complex feedback structures. In order to meet these challenges, we have to develop suitable inferential tools and here, in particular, we illustrate the use of approximate Bayesian computation and unscented Kalman filtering-based approaches. These partly complementary methods allow us to tackle a number of recurring problems in the design of biological systems. After a brief exposition of these two methodologies, we focus on their application to oscillatory systems."
"With the recent launch of MIT’s Institute for Medical Engineering and Science, MIT News examines research with the potential to reshape medicine and health care through new scientific knowledge, novel treatments and products, better management of medical data, and improvements in health-care delivery.
In the 1970s and 1980s, tissue engineers began working on growing replacement organs for transplantation into patients. While scientists are still targeting that goal, much of the tissue engineering research at MIT is also focused on creating tissue that can be used in the lab to model human disease and test potential new drugs. This kind of disease modeling could have a great impact in the near term, says MIT professor Sangeeta Bhatia, who is developing liver tissue to study hepatitis C and malaria infection.
Like other human tissues, liver is difficult to grow outside the human body because cells tend to lose their function when they lose contact with neighboring cells. “The challenge is to grow the cells outside the body while maintaining their function after being removed from their usual microenvironment,” says Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science..."
by Jean-Philippe J. Sobczak, Thomas G. Martin, Thomas Gerling, Hendrik Dietz
"We demonstrate that, at constant temperature, hundreds of DNA strands can cooperatively fold a long template DNA strand within minutes into complex nanoscale objects. Folding occurred out of equilibrium along nucleation-driven pathways at temperatures that could be influenced by the choice of sequences, strand lengths, and chain topology. Unfolding occurred in apparent equilibrium at higher temperatures than those for folding. Folding at optimized constant temperatures enabled the rapid production of three-dimensional DNA objects with yields that approached 100%. The results point to similarities with protein folding in spite of chemical and structural differences. The possibility for rapid and high-yield assembly will enable DNA nanotechnology for practical applications."
by Jay D. Keasling, Abraham Mendoza & Phil S. Baran
"Synthetic chemistry has long been used to prepare useful compounds — especially those that are hard to obtain from natural sources. But synthetic biology is coming of age as an alternative strategy. A biologist and two chemists debate the merits of their fields' synthetic prowess....."
*Synthetic Biology for Synthetic Chemistry* by Jay D. Keasling
"The richness and versatility of biological systems make them ideally suited to solve some of the world’s most significant challenges, such as converting cheap, renewable resources into energy-rich molecules; producing high-quality, inexpensive drugs to fight disease; and remediating polluted sites. Over the years, significant strides have been made in engineering microorganisms to produce fuels, bulk chemicals, and valuable drugs from inexpensive starting materials; to detect and degrade nerve agents as well as less toxic organic pollutants; and to accumulate metals and reduce radionuclides. The components needed to engineer the chemistry inside a microbial cell are significantly different from those commonly used to overproduce pharmaceutical proteins. Synthetic biology has had and will continue to have a significant impact on the development of these components to engineer cellular metabolism and microbial chassis to host the chemistry. The ready availability of more well-characterized gene expression components and hosts for chemical synthesis, standards for the connection of these components to make larger functioning devices, computer-aided design software, and debugging tools for biological designs will decrease both the time and the support needed to construct these designs. Some of the most important tools for engineering bacterial metabolism and their use for production of the antimalarial drug artemisinin are reviewed." http://bit.ly/ZpzUrx
"What if you could fashion a molecular system that could fight iron deficiency in developing nations? A system that could be grown and distributed in something as simple as yogurt.
Sound like a long shot? Well, a team of Northwestern University undergraduate students did just that this past October to win the gold medal at the regional level of the International Genetically Engineered Machine competition (iGEM). Using a mix-and-match collection of chemicals found in nature, the team developed a compound that lets the body break down phytic acid in the digestive system, which, in turn, releases iron and other useful nutrients. The kicker is that the system can be grown in yogurt – enabling a cheap and easy form of distribution to people in the developing world that need it the most. Iron deficiency is a problem that affects more than 30 percent of the world’s population, primarily in poor nations. This is just one example of the promise of synthetic biology. The emerging field blends engineering, biology and chemistry together in a way that allows scientists to essentially custom-tailor organisms, enabling them to function in desirable ways that they wouldn’t otherwise be able to do. ..."
Soon we'll be able to engineer living things with mechanical precision, says Tom Knight, father of synthetic biology
Gerd Moe-Behrens's insight:
by Andy Coghlan
"Soon we'll be able to engineer living things with mechanical precision, says Tom Knight, father of synthetic biology
How is synthetic biology different from biotechnology?The main difference is the degree of control. Engineers want their inventions to be as predictable and free from complexity as possible. That's what makes the approach of equipping living things with standardised DNA modules called BioBricks - of which some 15,000 are now available in an open-source registry - different from the prevailing biotechnological practice of inserting single genes randomly into living things. The key realisation is that biology is a manufacturing capability. We can have it build the things we want. How do you feel when people call you the "father of synthetic biology"?It's everyone's dream to see ideas that have become popular inspire research projects and students. I've been lucky to see both things happen through the International Genetically Engineered Machines (iGEM) competition for students, which I helped inaugurate in 2004. The 2012 winners have just been announced. What entry among the hundreds submitted over the years has inspired you most?A bacterium-based test that makes water samples change colour if arsenic is present at potentially dangerous levels. This combines an application that is socially valuable and responsible with impressive biology, some attention to economics and an ability to carry a project to a place, such as Bangladesh, where it works and is needed. And what has the craziest entry been?A project by artist Alexandra Daisy Ginsberg, in which she engineered E. coli to produce coloured pigments. The idea was to develop a daily probiotic drink that would show, by changing the colour of your poo, if you have an infection....."
"Regulatory networks are able to process complex signals and respond appropriately to the cellular context. Thus, an increasing effort by systems biology researchers is being focused on understanding which interactions are responsible for a given functional response. When translated into specific mathematical models, however, it has been repeatedly shown that this mapping between topology and function is not one-to-one, even for the simplest networks. Moreover, dynamical behavior may play an important role which is necessary to integrate in the general picture. We propose a unified theoretical/statistical approach to characterize the structure–function relationship in molecular networks when temporal features of both input signal and output response are important. The theory allows fast computation of network responses in terms of interaction strengths irrespective of molecular details, while statistical analysis identifies constraints between structural and dynamical features and network function. Investigating different feedback and feedforward loop architectures, we find that processing of temporal signals is strongly correlated to certain combinations of structural and dynamical characteristics, rather than to individual interactions. Our analysis offers new insight into the structure–function relationship in network motifs, quantifying how much the tuning of specific interactions affects network outcome, identifying key structural parameters for a given response and relating dynamics to network topology and function. This kind of analyses can be especially useful for synthetic biology approaches, where promoter libraries with a range of inputs and outputs can be engineered, and one has to choose the correct component needed to produce the desired network function." http://rsc.li/SQS4x9
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