Thursday, September 24, 2015

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



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 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."


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

Tuesday, September 8, 2015

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"]MIT Researchers Develop Basic Computing Elements for Bacteria 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