Synthetic Biology Needs Safety and Stability before Real World Application

Synthetic biology needs robust safety mechanisms before real world application

Ethics and technology hold the key to the success of synthetic biology

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Amsterdam

September 16, 2015

Targeted cancer treatments, toxicity sensors and living factories: synthetic biology has the potential to revolutionize science and medicine. But before the technology is ready for real-world applications, more attention needs to be paid to its safety and stability, say experts in a review article published in Current Opinion in Chemical Biology.

[caption id="attachment_270" align="aligncenter" width="560"] Synthetic Biology Needs Safety and Stability before Real World Application[/caption]

Synthetic biology involves engineering microbes like bacteria to program them to behave in certain ways. For example, bacteria can be engineered to glow when they detect certain molecules, and can be turned into tiny factories to produce chemicals.

Synthetic biology has now reached a stage where it's ready to move out of the lab and into the real world, to be used in patients and in the field. According to Professor Pamela Silver, one of the authors of the article from Harvard Medical School in the US, this move means researchers should increase focus on the safety of engineered microbes in biological systems like the human body.

"Historically, molecular biologists engineered microbes as industrial organisms to produce different molecules," said Professor Silver. "The more we discovered about microbes, the easier it was to program them. We've now reached a very exciting phase in synthetic biology where we're ready to apply what we've developed in the real world, and this is where safety is vital."

Microbes have an impact on health; the way they interact with animals is being ever more revealed by microbiome research - studies on all the microbes that live in the body - and this is making them easier and faster to engineer. Scientists are now able to synthesize whole genomes, making it technically possible to build a microbe from scratch.

"Ultimately, this is the future - this will be the way we program microbes and other cell types," said Dr. Silver. "Microbes have small genomes, so they're not too complex to build from scratch. That gives us huge opportunities to design them to do specific jobs, and we can also program in safety mechanisms."

One of the big safety issues associated with engineering microbial genomes is the transfer of their genes to wild microbes. Microbes are able to transfer segments of their DNA during reproduction, which leads to genetic evolution. One key challenge associated with synthetic biology is preventing this transfer between the engineered genome and wild microbial genomes.

There are already several levels of safety infrastructure in place to ensure no unethical research is done, and the kinds of organisms that are allowed in laboratories. The focus now, according to Dr. Silver, is on technology to ensure safety. When scientists build synthetic microbes, they can program in mechanisms called kill switches that cause the microbes to self-destruct if their environment changes in certain ways.

Microbial sensors and drug delivery systems can be shown to work in the lab, but researchers are not yet sure how they will function in a human body or a large-scale bioreactor. Engineered organisms have huge potential, but they will only be useful if proven to be reliable, predictable, and cost effective. Today, engineered bacteria are already in clinical trials for cancer, and this is just the beginning, says Dr. Silver.

"The rate at which this field is moving forward is incredible. I don't know what happened - maybe it's the media coverage, maybe the charisma - but we're on the verge of something very exciting. Once we've figured out how to make genomes more quickly and easily, synthetic biology will change the way we work as researchers, and even the way we treat diseases."

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Read the story on Elsevier Connect

Article details

"Synthetic biology expands chemical control of microorganisms" by Tyler J Ford and Pamela A Silver (doi: 10.1016/j.cbpa.2015.05.012). The article appears in Current Opinion in Chemical Biology, Volume 28 (October 2015), published by Elsevier.

News Release Source : Synthetic biology needs robust safety mechanisms before real world application

MIT Researchers Develop Basic Computing Elements for Bacteria

Researchers develop basic computing elements for bacteria

MIT July 9, 2015

The “friendly” bacteria inside our digestive systems are being given an upgrade, which may one day allow them to be programmed to detect and ultimately treat diseases such as colon cancer and immune disorders.

[caption id="attachment_264" align="aligncenter" width="650"] The illustration depicts Bacteroides thetaiotaomicron (white) living on mammalian cells in the gut (large pink cells coated in microvilli) and being activated by exogenously added chemical signals (small green dots) to express specific genes, such as those encoding light-generating luciferase proteins (glowing bacteria).[/caption]

In a paper published today in the journal Cell Systems, researchers at MIT unveil a series of sensors, memory switches, and circuits that can be encoded in the common human gut bacterium Bacteroides thetaiotaomicron.

These basic computing elements will allow the bacteria to sense, memorize, and respond to signals in the gut, with future applications that might include the early detection and treatment of inflammatory bowel disease or colon cancer.

Researchers have previously built genetic circuits inside model organisms such as E. coli. However, such strains are only found at low levels within the human gut, according to Timothy Lu, an associate professor of biological engineering and of electrical engineering and computer science, who led the research alongside Christopher Voigt, a professor of biological engineering at MIT.

“We wanted to work with strains like B. thetaiotaomicron that are present in many people in abundant levels, and can stably colonize the gut for long periods of time,” Lu says.

The team developed a series of genetic parts that can be used to precisely program gene expression within the bacteria. “Using these parts, we built four sensors that can be encoded in the bacterium’s DNA that respond to a signal to switch genes on and off inside B. thetaiotaomicron,” Voigt says. These can be food additives, including sugars, which allow the bacteria to be controlled by the food that is eaten by the host, Voigt adds.

Bacterial “memory”

To sense and report on pathologies in the gut, including signs of bleeding or inflammation, the bacteria will need to remember this information and report it externally. To enable them to do this, the researchers equipped B. thetaiotaomicron with a form of genetic memory. They used a class of proteins known as recombinases, which can record information into bacterial DNA by recognizing specific DNA addresses and inverting their direction.

The researchers also implemented a technology known as CRISPR interference, which can be used to control which genes are turned on or off in the bacterium. The researchers used it to modulate the ability of B. thetaiotaomicron to consume a specific nutrient and to resist being killed by an antimicrobial molecule.

The researchers demonstrated that their set of genetic tools and switches functioned within B. thetaiotaomicroncolonizing the gut of mice. When the mice were fed food containing the right ingredients, they showed that the bacteria could remember what the mice ate.

Expanded toolkit

The researchers now plan to expand the application of their tools to different species of Bacteroides. That is because the microbial makeup of the gut varies from person to person, meaning that a particular species might be the dominant bacteria in one patient, but not in others.

“We aim to expand our genetic toolkit to a wide range of bacteria that are important commensal organisms in the human gut,” Lu says.

The concept of using microbes to sense and respond to signs of disease could also be used elsewhere in the body, he adds.

In addition, more advanced genetic computing circuits could be built upon this genetic toolkit in Bacteroides to enhance their performance as noninvasive diagnostics and therapeutics.

“For example, we want to have high sensitivity and specificity when diagnosing disease with engineered bacteria,” Lu says. “To achieve this, we could engineer bacteria to detect multiple biomarkers, and only trigger a response when they are all present.”

Tom Ellis, group leader of the Centre for Synthetic Biology at Imperial College London, who was not involved in the research, says the paper takes many of the best tools that have been developed for synthetic biology applications with E. coli and moves them over to use with a common class of gut bacteria.

“Whereas others have developed tools and applications for engineering genetic circuits, or biosensors, in bacteria that are then placed in the gut, this paper stands out from the crowd by first engineering a member of the Bacteroides genus, the most common type of bacteria found in our guts,” Ellis says. The study has so far shown the efficacy of the approach in mice, and there will be a long road ahead before it can be approved for use in humans, Ellis says.

However, the paper really opens up the possibility of one day having engineered cells resident in our guts for long periods of time, he says. “These could do tasks like sensing and recording, or even in-situ synthesis of therapeutic molecules as and when they are needed.”

News Release Source : Researchers develop basic computing elements for bacteria

Image Credit : MIT

Synthetic Biology Students Compete in iGEM 2015

Synthetic Biology Students Compete in iGEM 2015 Giant Jamboree

12th annual conference and competition to showcase student innovations in genetically engineered biological systems

CAMBRIDGE, Mass., Aug. 5, 2015 /PRNewswire/

iGEM, the largest synthetic biology community and premiere synthetic biology competition, today announced that more than 250 student-led teams will present their innovations at the iGEM Giant Jamboree,September 24-28, 2015 at the Hynes Convention Center in Boston, MA. The 12^th annual iGEM 2015 Giant Jamboree gathers the industry's brightest minds for a five-day conference to collaborate on education and advancement of the synthetic biology field.

[caption id="attachment_256" align="aligncenter" width="722"] Synthetic Biology Students Compete in iGEM 2015[/caption]

Over 4600 participants on 280 teams registered to take part in the 2015 competition. Teams represent countries across the world including North America (82), Latin America (20), Europe (72), Asia (104), and Africa (2). Students' knowledge of synthetic biology is put to the ultimate test as teams work for months to solve real-world challenges by creating novel genetically engineered systems. Their local experiences in a global community impart unique perspective in the field, especially as projects span a broad range across 15 different tracks —including energy, environment, food and nutrition, manufacturing, health and medicine, community labs, among others.

After receiving a standard kit of BioBrick biological parts from the iGEM Registry of Standard Biological Parts, an open library of biological parts that can be mixed and matched to build synthetic biology devices and systems, each team manages their own projects, advocates for their research, and secures funding. Teams are also challenged to actively consider and address the safety, security and environmental implications of their work.

"Much more than an annual student competition, the iGEM Giant Jamboree is also an international incubator for the synthetic biology industry that has spun out more than 20 competition projects into new startups," said Randy Rettberg, iGEM Foundation president. "With a spotlight on innovation, the iGEM Giant Jamboree also is about collaboration and giving back. iGEM competition teams submit biological parts from their projects to the Registry of Standard Biological Parts in a cycle that helps tomorrow's iGEM teams and research labs."

The iGEM Giant Jamboree five-day conference features today's leaders in synthetic biology. Team presentations and exhibition hall poster sessions showcase the latest research. Workshops, panel discussions and much more inspire and educate future synthetic biologists, introducing the next generation of elite researchers and scientists—the entrepreneurs, lab leaders, and workforce of biotechnology's future. The competition and conference concludes with an awards gala where winners will be presented on Monday, September 28.  Through the iGEM competition, the iGEM Foundation promotes education, safety and security, policy and regulation, multidisciplinary teamwork, technology, community, and open sharing.

Additional Resources

• iGEM Press Kit and Photos: http://www.igem.org/Press_Kit


• 2015 iGEM Giant Jamboree Brochure: full details on the conference & competition, from event program, to registration, sponsorship and more: http://2015.igem.org/Giant_Jamboree


• 2014 iGEM Giant Jamboree Booklet: Read about real-world solutions from last year's competition:http://2014.igem.org/Giant_Jamboree/Booklet


• iGEM Registry of Standard Biological Parts: http://parts.igem.org

About the iGEM Foundation
The iGEM Foundation is dedicated to education and competition, advancement of synthetic biology, and the development of open community and collaboration. iGEM, the International Genetically Engineered Machine Competition, is a non-profit organization that inspires future synthetic biologists by hosting high school and collegiate level competitions in synthetic biology. iGEM also maintains the Registry of Standard Biological Parts with over 20,000 specified genetic parts—the world's largest collection of BioBricks, open source DNA parts.

SOURCE iGEM
RELATED LINKS
http://igem.org

News Release Source : Synthetic Biology Students Compete in iGEM 2015 Giant

Image Credit : iGEM

Scientists Believe Synthetic Biology a Key to Long-term Manned Space Missions

Synthetic biology for space exploration

Berkeley Lab scientists believe biomanufacturing a key to long-term manned space missions

DOE/LAWRENCE BERKELEY NATIONAL LABORATORY

Does synthetic biology hold the key to manned space exploration of Mars and the Moon? Berkeley Lab researchers have used synthetic biology to produce an inexpensive and reliable microbial-based alternative to the world's most effective anti-malaria drug, and to develop clean, green and sustainable alternatives to gasoline, diesel and jet fuels. In the future, synthetic biology could also be used to make manned space missions more practical.

[caption id="attachment_250" align="aligncenter" width="650"] Scientists Believe Synthetic Biology a Key to Long-term Manned Space Missions[/caption]

"Not only does synthetic biology promise to make the travel to extraterrestrial locations more practical and bearable, it could also be transformative once explorers arrive at their destination," says Adam Arkin, director of Berkeley Lab's Physical Biosciences Division (PBD) and a leading authority on synthetic and systems biology.

"During flight, the ability to augment fuel and other energy needs, to provide small amounts of needed materials, plus renewable, nutritional and taste-engineered food, and drugs-on-demand can save costs and increase astronaut health and welfare," Arkin says. "At an extraterrestrial base, synthetic biology could even make more effective use of the catalytic activities of diverse organisms."

Arkin is the senior author of a paper in the Journal of the Royal Society Interface that reports on a techno-economic analysis demonstrating "the significant utility of deploying non-traditional biological techniques to harness available volatiles and waste resources on manned long-duration space missions." The paper is titled "Towards Synthetic Biological Approaches to Resource Utilization on Space Missions." The lead and corresponding author is Amor Menezes, a postdoctoral scholar in Arkin's research group at the University of California (UC) Berkeley. Other co-authors are John Cumbers and John Hogan with the NASA Ames Research Center.

One of the biggest challenges to manned space missions is the expense. The NASA rule-of-thumb is that every unit mass of payload launched requires the support of an additional 99 units of mass, with "support" encompassing everything from fuel to oxygen to food and medicine for the astronauts, etc. Most of the current technologies now deployed or under development for providing this support are abiotic, meaning non-biological. Arkin, Menezes and their collaborators have shown that providing this support with technologies based on existing biological processes is a more than viable alternative.

"Because synthetic biology allows us to engineer biological processes to our advantage, we found in our analysis that technologies, when using common space metrics such as mass, power and volume, have the potential to provide substantial cost savings, especially in mass," Menezes says.

In their study, the authors looked at four target areas: fuel generation, food production, biopolymer synthesis, and pharmaceutical manufacture. They showed that for a 916 day manned mission to Mars, the use of microbial biomanufacturing capabilities could reduce the mass of fuel manufacturing by 56-percent, the mass of food-shipments by 38-percent, and the shipped mass to 3D-print a habitat for six by a whopping 85-percent. In addition, microbes could also completely replenish expired or irradiated stocks of pharmaceuticals, which would provide independence from unmanned re-supply spacecraft that take up to 210 days to arrive.

"Space has always provided a wonderful test of whether technology can meet strict engineering standards for both effect and safety," Arkin says. "NASA has worked decades to ensure that the specifications that new technologies must meet are rigorous and realistic, which allowed us to perform up-front techno-economic analysis."

The big advantage biological manufacturing holds over abiotic manufacturing is the remarkable ability of natural and engineered microbes to transform very simple starting substrates, such as carbon dioxide, water biomass or minerals, into materials that astronauts on long-term missions will need. This capability should prove especially useful for future extraterrestrial settlements.

"The mineral and carbon composition of other celestial bodies is different from the bulk of Earth, but the earth is diverse with many extreme environments that have some relationship to those that might be found at possible bases on the Moon or Mars," Arkin says. "Microbes could be used to greatly augment the materials available at a landing site, enable the biomanufacturing of food and pharmaceuticals, and possibly even modify and enrich local soils for agriculture in controlled environments."

The authors acknowledge that much of their analysis is speculative and that their calculations show a number of significant challenges to making biomanufacturing a feasible augmentation and replacement for abiotic technologies. However, they argue that the investment to overcome these barriers offers dramatic potential payoff for future space programs.

"We've got a long way to go since experimental proof-of-concept work in synthetic biology for space applications is just beginning, but long-duration manned missions are also a ways off," says Menezes. "Abiotic technologies were developed for many, many decades before they were successfully utilized in space, so of course biological technologies have some catching-up to do. However, this catching-up may not be that much, and in some cases, the biological technologies may already be superior to their abiotic counterparts."

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This research was supported by the National Aeronautics and Space Administration (NASA) and the University of California, Santa Cruz.

Lawrence Berkeley National Laboratory addresses the world's most urgent scientific challenges by advancing sustainable energy, protecting human health, creating new materials, and revealing the origin and fate of the universe. Founded in 1931, Berkeley Lab's scientific expertise has been recognized with 13 Nobel prizes. The University of California manages Berkeley Lab for the U.S. Department of Energy's Office of Science. For more, visit http://www.lbl.gov.

News Release Source :  Synthetic biology for space exploration

Image Credit : NASA