SynBioFromLeukipposInstitute

by
Arkin AP.

"The next generation of synthetic biology applications will increasingly involve engineered organisms that exist in intimate contact with humans, animals and the rest of the environment. Examples include cellular and viral approaches for maintaining and improving health in humans and animals. The need for reliable and specific function in these environments may require more complex system designs than previously. In these cases the uncertainties in the behavior of biological building blocks, their hosts and their environments present a challenge for design of predictable and safe systems. Here, we review systematic methods for the effective characterization of these uncertainties that are lowering the barriers to predictive design of reliable complex biological systems."

 http://bit.ly/1aVSDig

by
Vijai Singh

"Synthetic biology is the design and construction of new biological parts, devices and circuits not existing in nature. It provides a novel solution to imminent challenges in a wide variety of fields, including the discovery of new drugs, production chemicals, renewable biofuels, value-added products and cellular reprogramming. Many efforts have been made to design and characterize synthetic genetic parts, including promoter, transcription factors, RBS, degradation tags and transcriptional terminators, among others. These genetic parts have been assembled for construction of a number of synthetic devices and circuits like oscillators, toggle switches, amplifiers and biologic gates; they play a vital role in cell reprogramming for better understanding of cellular mechanisms and control of biological process. They are also useful for the periodic and tunable production of drugs, fine chemicals, vaccines and much more. It is the goal of this review to aid and accelerate future research in synthetic biology."

 http://bit.ly/1ic63Nz

http://bit.ly/1dw2GPA

by
Joe Kullman

"ASU synthetic biologist Karmella Haynes is participating in a national research project to help battle diabetes. Her role involves developing advanced ways of revealing fundamental factors that determine the health of the body’s cells.

In her synthetic biology lab, Karmella Haynes focuses much of her effort on developing better ways of exploring how human body cells work – or don’t work like they should. She’ll be applying her expertise in that area to a major new research endeavor to produce more effective treatments for diabetes.
The project is being undertaken by the national Synthetic Biology Engineering Research Center (SynBERC), which is supported by the National Science Foundation (NSF). SynBERC members include the Massachusetts Institute of Technology (MIT), Harvard Medical School and Stanford University.
Haynes became an affiliate researcher for the center as a result of the synthetic biology research she conducted at Harvard before joining Arizona State University, where she is an assistant professor in the School of Biological and Health Systems Engineering, one of ASU’s Ira A. Fulton Schools of Engineering.  
The NSF recently awarded her an $81,000 grant to support her role in the project. She will seek to develop more advanced synthetic monitors to track the development and health conditions of body cells.
In this case, Haynes will zero in on pancreatic islets cells – tiny clumps of cells in the pancreas that produce glucagon and insulin, which helps the body burn sugar and maintain blood sugar levels.
“When something goes wrong within these clumps of cells, you develop diseases such as diabetes,” she explains.
Diabetes is a major disabling and deadly disease that is projected to afflict about 300 million people by 2025, according to the World Health Organization.
Glucagon is a peptide hormone that the pancreas secretes. It raises blood glucose levels – the opposite of the function of insulin, which lowers blood glucose levels.
Haynes will grow pancreatic cells that produce glucagon and insulin in an artificial culture (outside the body), enabling her to study the effects of particular synthetic proteins and DNA on those cells.
In the past, such cell cultures have been grown on flat surfaces. Haynes will collaborate with labs at MIT to grow and study the cells in a three-dimensional translucent biomaterial.
Being able to make observations from a three-dimensional view “gives us a much more holistic view of how treatments affect the pancreatic islet tissue, and of ways we can genetically manipulate cells so a disease can be treated effectively,” she explains. “We can gain a deeper understanding of the proper growth process of that small mass of pancreatic cells that is critical in preventing development of diabetes.”
The cells themselves will be implanted with synthetic monitors capable of tracking changes in the chromosomal structure of the cells. That will give Haynes a precise look at various stages of cell development.
She will be designing the synthetic proteins that act as monitors, revealing “the molecular changes that occur in the cells as they grow” and allowing her “to manipulate the states of the cells to maintain healthy pancreatic tissue.”
The DNA-based monitoring device signals what it finds by glowing – enabled by the use of a genetically encoded fluorescent protein that the monitor can produce.
“We can engineer the DNA-based monitor so that when the chromosome structure of the cells changes, the monitor is tripped and starts producing a green fluorescent protein,” Haynes explains. “Certain changes in chromosome structure can promote cell viability or cause cell death.”
The process enables close tracking of the condition of the coiled material in the chromosomal structure of pancreatic cells. If the coils become too loose or too condensed, they can interfere with insulin production or other proper functions of the pancreas.
Haynes’ says one of her project‘s goals is “revealing the physics underlying the coiling and uncoiling of these strands of DNA” and using that knowledge to “design small proteins that go into cells and actually control the coiling and uncoiling of DNA so that the pancreas islets have plenty of cells that are producing proper levels of insulin.”
A portion of her NSF grant will support students in getting hands-on lab experience. One undergraduate and one graduate student will be part of Haynes’ SynBERC project research team."

 http://bit.ly/1eksUAS

by
Cleo Kontoravdi

"Synthetic biology gives researchers the opportunity to rationally (re-)design cellular activities to achieve a desired function. The design of networks of pathways towards accomplishing this calls for the application of engineering principles, often using model-based tools. Success heavily depends on model reliability. Herein, we present a systematic methodology for developing predictive models comprising model formulation considerations, global sensitivity analysis, model reduction (for highly complex models or where experimental data are limited), optimal experimental design for parameter estimation, and predictive capability checking. Its efficacy and validity are demonstrated using an example from bioprocessing. This approach systematizes the process of developing reliable mathematical models at a minimum experimental cost, enabling in silico simulation and optimization."

 http://bit.ly/18w2fO0

by
Deborah Williams-Hedges

"A new method that uses a lab-on-a-chip device and a smartphone is able to count molecules—such as HIV RNA—in a sample.

 In developing nations, rural areas, and at home, limited access to expensive equipment and trained medical professionals can impede the diagnosis and treatment of disease.

Many qualitative tests that provide a simple “yes” or “no” answer—like an at-home pregnancy test—have been optimized for use in these resource-limited settings. But few quantitative tests—those able to measure the precise concentration of biomolecules, not just their presence or absence—can be done outside of a laboratory or clinical setting. Researchers say their new digital approach can consistently provide accurate quantitative information despite changes in timing, temperature, and lighting conditions, a capability not previously possible using traditional measurements...."

 http://bit.ly/18lLcB9

by
Wade Grabow and Luc Jaeger

"RNA molecules are highly modular components that can be used in a variety of contexts for building new metabolic, regulatory and genetic circuits in cells. The majority of synthetic RNA systems to date predominately rely on two-dimensional modularity. However, a better understanding and integration of three-dimensional RNA modularity at structural and functional levels is critical to the development of more complex, functional bio-systems and molecular machines for synthetic biology applications."


 http://bit.ly/18NtvqP

by
Harry Binswanger

"Echoing the “soup Nazi” on Seinfeld, the Food and Drug Administration bureaucrats have just declared: No gene test for you.

The FDA sent a strongly worded cease-and-desist letter to gene-testing pioneer 23andMe, a company that offers genetic testing of your DNA for only $99. (The firm’s name capitalizes on the 23 chromosomes that make up the human genome.) So far, almost half a million individuals have used 23andMe’s genetic test kit. Clients mail a saliva sample to the company for laboratory analysis. But if the FDA’s power-grab succeeds, this innovative, inexpensive means of getting on top of your own genetic makeup, learning about your susceptibility to various diseases and pharmaceuticals, will be stopped indefinitely. On Twitter, one of 23andMe’s co-founders nailed it: “So much for patient empowerment.” What is the FDA’s rationale for blocking this medical advance? The idea is that some people will misuse the information. The FDA’s letter to 23andMe calls “particularly concerning” the information the tests would provide about the gene linked to breast cancer (BRCA) “because of the potential health consequences that could result from false positive or false negative assessments.” Patients may undergo mastectomies that the FDA deems unwarranted. What the FDA is evading is that test results do not by themselves produce “consequences.” Between the data and the action taken lies the human mind. Your mind. After you open a letter or an email from 23andMe, what you then do depends upon how and whether you think. A false positive does not force you to obey it. A rational, responsible person talks over the test results with his doctor. If the test results are significant, he may need to have a second test done. But here is the FDA’s implied image of how things go. Jane Doe gets her 23andMe test results and leaps into action. She Googles: “surgery cheap,” finds a guy working out of his station wagon, and has him perform a prophylactic mastectomy on her. Is that how the world works? Is that the view of woman that we all must be forcibly leveled down to? In the real world, what would happen is this. The woman goes to her doctor. He orders up another, more precise test. Depending on his judgment of the results, he may refer her to a surgeon. Note the involvement of the mind throughout: the woman makes judgments, the doctor makes judgments, the surgeon makes judgments. (And what insurer is going to pay for the hugely expensive surgery based only on one spit-test-by-mail result?) But let’s suppose that some irrational woman somewhere does find a back-alley surgeon, who doesn’t work by doctor-referral, and she pays out of her own pocket for what is, in rational terms, a needless mastectomy. The question is: should the rest of us be sacrificed to prevent her from bearing the logical consequences of her own irrationality? Is the health of the wise and responsible to be sacrificed to protect the divine right of impulsive stupidity? The gene-test results form only part of the story. The full context includes many other factors, especially the reliability of those results. The responsibility of 23andMe is to send, along with test results, statistics on how often such results are in error. The full truth is the test results discounted by the chance of false positives or false negatives. But the FDA is not calling for disclosure. They are not concerned with the full truth. Their message to the world is: “You’re not able to handle the truth. Only we in the FDA can decide what is true and rational. You may think you are proceeding rationally, but that’s not good enough. We decide what’s rational for you and what is not.” Incidentally, the government’s own website, cancer.gov, says “Finally, there is a small chance [my emphasis] that test results may not be accurate, leading people to make decisions based on incorrect information. Although inaccurate results are unlikely, people with these concerns should bring them up during genetic counseling.” The real issue is not the reliability of these tests. The real issue is the right of an individual to act on his own judgment, free of government coercion. The FDA is waging war against the mind of the individual. The mind is a terrible thing to lay to waste."

http://onforb.es/18HP7bM ;

by
Ronald W. Ellis

"Over the last few years, the chemical synthesis of DNA in vitro has become a routine technique. The ready availability of synthetic DNA has revolutionized molecular biological research and has enabled new research approaches to be attempted that had not been possible previously. The most commonly used approaches can be divided into three broad areas: the cloning and manipulation of genes, the diagnosis of diseases by probing gene structure, and the specific in vitro mutagenesis of DNA for structure/function studies. In this review, each of these three areas is discussed through specific applications from published work. This review is not intended to be comprehensive either in its scope or in its documentation of published results. Rather, it is meant to present some of the most commonly used applications of oligonucleotides in molecular biology through representative examples."

http://bit.ly/1bSo3np

by
van Doren D, Koenigstein S, Reiss T.

"In the past decades, synthetic biology has gained interest regarding research and development efforts within the biotechnology domain. However, it is unclear to what extent synthetic biology has matured already into being commercially exploitable. By means of a patent analysis, this study shows that there is an increasing trend regarding synthetic biology related patent applications. The majority of retrieved patents relates to innovations facilitating the realisation of synthetic biology through improved understanding of biological systems. In addition, there is increased activity concerning the development of synthetic biology based applications. When looking at potential application areas, the majority of synthetic biology patents seems most relevant for the medical, energy and industrial sector. Furthermore, the analysis shows that most activity has been carried out by the USA, with Japan and a number of European countries considerably trailing behind. In addition, both universities and companies are major patent applicant actor types. The results presented here form a starting point for follow-up studies concerning the identification of drivers explaining the observed patent application trends in synthetic biology."

http://bit.ly/1aVcpa8

by
Ryback BM, Odoni DI, van Heck RG, van Nuland Y, Hesselman MC, Martins Dos Santos VA, van Passel MW, Hugenholtz F.

"BACKGROUND:

The use of in silico simulations as a basis for designing artificial biological systems (and experiments to characterize them) is one of the tangible differences between Synthetic Biology and "classical" Genetic Engineering. To this end, synthetic biologists have adopted approaches originating from the traditionally non-biological fields of Nonlinear Dynamics and Systems & Control Theory. However, due to the complex molecular interactions affecting the emergent properties of biological systems, mechanistic descriptions of even the simplest genetic circuits (transcriptional feedback oscillators, bi-stable switches) produced by these methods tend to be either oversimplified, or numerically intractable. More comprehensive and realistic models can be approximated by constructing "toy" genetic circuits that provide the experimenter with some degree of control over the transcriptional dynamics, and allow for experimental set-ups that generate reliable data reflecting the intracellular biochemical state in real time. To this end, we designed two genetic circuits (basic and tunable) capable of exhibiting synchronized oscillatory green fluorescent protein (GFP) expression in small populations of Escherichia coli cells. The functionality of the basic circuit was verified microscopically. High-level visualizations of computational simulations were analyzed to determine whether the reliability and utility of a synchronized transcriptional oscillator could be enhanced by the introduction of chemically inducible repressors.RESULTS:Synchronized oscillations in GFP expression were repeatedly observed in chemically linked sub-populations of cells. Computational simulations predicted that the introduction of independently inducible repressors substantially broaden the range of conditions under which oscillations could occur, in addition to allowing the frequency of the oscillation to be tuned.CONCLUSIONS:The genetic circuits described here may prove to be valuable research tools for the study of synchronized transcriptional feedback loops under a variety of conditions and experimental set-ups. We further demonstrate the benefit of using abstract visualizations to discover subtle non-linear trends in complex dynamic models with large parameter spaces."

http://bit.ly/188C7hi

Free PDF
http://bit.ly/1jn4qIe

By Jef Akst

"Biological tinkerers are not the risk that some have made them out to be, according to a new report.

Amateur biologists working in community do-it-yourself (DIY) laboratories—or even their own garages—are unlikely to pose a serious threat to society, according to a report released today (November 19) by the Synthetic Biology Project at the Woodrow Wilson International Center for Scholars in Washington, DC. “There’s been a lot of debate in the biosecurity community about what DIYers may or may not be doing, from making narcotics to pandemics to viruses that kill heads of state (I’m not joking),” Wilson fellow Daniel Grushkin, a coauthor of the new report, wrote in an e-mail to ScienceInsider. Indeed, many have debated the need for greater oversight of such DIY efforts. But the Synthetic Biology Project’s survey of the DIYbio community suggests that such fears are unfounded, and Grushkin hopes researchers will start to focus on the opportunities that the DIY community represents, including improving science education and awareness, and perhaps even advancing technology and research. “[Some] believe DIYbio can inspire a generation of bioengineers to discover new medicines, customize crops to feed the world’s exploding population, harness microbes to sequester carbon, solve the energy crisis, or even grow our next building materials,” Grushkin and his coauthors wrote in the report. “Many Do-It-Yourself participants—or DIYers—believe that wider access to the tools of biotechnology, particularly those related to the reading and writing of DNA, has the potential to spur global innovation and promote biology education and literacy.” At the same time, the report cautions against believing the unproven hype often touted in some media reports. “The reality, as it stands, is that DIYbio is far more innocuous than either vision”—fear concerning such amateur-driven research or blind faith in its potential. According to the online survey, which received 359 responses from the DIY community, the vast majority of DIYers work in community labs, with less than 10 percent of respondents reporting doing work on their own at home. Moreover, while some reported fairly sophisticated projects, such as manufacturing PCR machines for a fraction of the retail cost, most amateur biologists reported doing harmless, basic experiments, such as DNA extraction from a cheek swab. The report also revealed that many DIYers are open to more formalized regulation of their work. While just 25 percent said they think such oversight is needed at the moment, about half of respondents noted it would likely become necessary in the future." 

 http://bit.ly/18QdtfC