"Previous efforts to control cellular behaviour have largely relied upon various forms of genetic engineering. Once the genetic content of a living cell is modified, the behaviour of that cell typically changes as well. However, other methods of cellular control are possible. All cells sense and respond to their environment. Therefore, artificial, non-living cellular mimics could be engineered to activate or repress already existing natural sensory pathways of living cells through chemical communication. Here we describe the construction of such a system. The artificial cells expand the senses of Escherichia coli by translating a chemical message that E. coli cannot sense on its own to a molecule that activates a natural cellular response. This methodology could open new opportunities in engineering cellular behaviour without exploiting genetically modified organisms."
by Benjamin Reeve, Theo Sanderson, Tom Ellis, Paul Freemont
"As our understanding of natural biological systems grows, so too does our ability to alter and rebuild them. Synthetic biology is the application of engineering principles to biology in order to design and construct novel biological systems for specific applications. Bioluminescent organisms offer a treasure trove of light-emitting enzymes that may have applications in many areas of bioengineering, from biosensors to lighting. A few select bioluminescent organisms have been well researched and the molecular and genetic basis of their luminescent abilities elucidated, with work underway to understand the basis of luminescence in many others. Synthetic biology will aim to package these light-emitting systems as self-contained biological modules, characterize their properties, and then optimize them for use in other chassis organisms. As this catalog of biological parts grows, synthetic biologists will be able to engineer complex biological systems with the ability to emit light. These may use luminescence for an array of disparate functions, from providing illumination to conveying information or allowing communication between organisms."
"Soon to be grown for ornamental use only.Credit: Mark Nesbitt and Samuel Delwen, CC BY
By Luc Henry, Swiss Federal Institute of Technology in Lausanne
The past few decades have seen enormous progress being made in synthetic biology – the idea that simple biological parts can be tweaked to do our bidding. One of the main targets has been hacking the biological machinery that nature uses to produce chemicals. The hope is – once we understand enough – we might be able to design processes that convert cheap feedstock, such as sugar and amino acids, into drugs or fuels. These production lines can then be installed into microbes, effectively turning living cells into factories.
Taking a leap in that direction, researchers from Stanford University have created a version of baker’s yeast (Saccharomyces cerevisiae) that contains genetic material of the opium poppy (Papaver somniferum), bringing the morphine microbial factory one step closer to reality. These results published in the journal Nature Chemical Biology represent a significant scientific success, but eliminating the need to grow poppies may still be years away.
More than bread and booze
If dog has been man’s best friend for thousands of years or more, the humble yeast has long been man’s second-best friend. The single-cell organism has been exploited by human societies to produce alcoholic beverages or bread for more than 4,000 years.
Like any animal or plant that mankind domesticated, there has been a particular interest in the study and optimisation of yeast. When breeding turned into a scientific discipline, it quickly became a model organism for biological experiments. And in 1996, its complete genome was the first sequenced from a eukaryotic organism – the more advanced tree of life. This extensive knowledge of yeast biology makes it an attractive platform for synthetic biology.
In the new study, Christina Smolke and her team further show that yeast could be a good candidate for the production of opioids – a class of drugs that includes morphine. To achieve this transformation, Smolke would need a complete biological pathway required to produce complex opioids.
In 2008 she got the first hint on successfully fermenting simple sugars to make salutaridine, an opioid precursor. Then in 2010, a Canadian team identified the last two missing pieces of the morphine puzzle in the genome of opium poppy.
Using these biological parts from plants, together with some from bacteria, Smolke has now created yeast that can produce many natural and unnatural opioids. All it takes is to feed the microbes an intermediary molecule extracted from the poppy plant called thebaine.
These results bring the technology one step closer to microbial factories that can produce pharmaceutical molecules in a tank rather than in the field. What is left now is for Smolke to find a way to turn salutaridine into thebaine efficiently. Filling this gap may allow her to create a yeast strain producing opioids directly from sugars.
Teaching yeast new tricks
There have been other synthetic biology landmarks in the past. In 2006, chemical engineer Jay Keasling of the University of California at Berkeley and his team successfully introduced genetic material from the sweet wormwood plant (Artemisia annual) into yeast. Their microbial factory was able to produce artemisinic acid, which is only one chemical step away from artemisinin, the most efficient drug against Plasmodium falciparum malaria...."
Our very own Timothy Ang featured on the great new blog "Humans and Synthetic Biology" by Cornell iGEM.... (Our very own Timothy Ang featured on the great new blog "Humans and Synthetic Biology" by Cornell iGEM....
"“Smart” bacteria that sense, track, pursue, fight and defeat infectious and other biological agents afflicting the warfighter might be closer to reality.
Building on earlier work focused on understanding how bacteria sense their nearest neighbors (including pathogens), a DTRA CB/JSTO-funded research team managed by DTRA CB’s Dr. Ilya Elashvili and led by Dr. William E. Bentley has paired with the Italian synthetic biology team headed by Dr. Sheref Mansy. The joint team created artificial cells that translate non-native signals into native signals that manipulate a local bacterial population.
These new tools have the potential to offer a means to localize bacteria and take actions to identify pathogens, other maladies (e.g., cancer cells), and synthesize drugs for local delivery and treatment.
Synthetic biology holds great promise to enable the engineering of “smart” bacteria that execute high order functions, such as those needed to sense, track, pursue, and fight pathogens. The Bentley lab focuses on minimally rewiring native cell processes so as not to “over engineer” these designer cells.
For example, they have built modules that recognize a pathogen’s signals and that rewire metabolic pathways to synthesize a pathogen-targeted drug. However, as these modules are pieced together and new modules are added, they impede other needed functions, such as swimming to or away from desired locales.
One way to counter unanticipated “side effects” is to employ small populations of orchestrated cells that act collectively to accomplish their task. Their plans, for example, call for “sentinel” and “dirigible” cells that find pathogens and call for backup.
In a recent Nature Communications article, “Integrating artificial with natural cells to translate chemical messages that direct E. coli behaviour,” the American-Italian joint team showed they were able to induce desired activity of native cells through communication with artificial cells.
The artificial cells, in turn, read a chemical cue foreign to the native cells and synthesized another compound recognized by the native cells. In this way, the artificial cells served as a translator. To the authors’ knowledge, this is the first artificial, cell-like system capable of translating unrecognized signals into a chemical language that natural cells can recognize.
The artificial non-living cell was built with a phospholipid vesicle containing isopropyl β-D-1-thiogalactopyranoside (IPTG), DNA, and transcription–translation machinery. The DNA template codes for a previously selected ribo-switch that activates translation in response to the presence of a model chemical signal molecule, theophylline.
Theophylline is added to the mixture, diffuses into the vesicle, and triggers the synthesis of the pore forming protein α-hemolysin (αHL). Therefore, only in the presence of theophylline a pore forms that releases entrapped IPTG.
Released IPTG will increase the transcription of a variety of genes induced by the lac operon in E. coli. IPTG is a model signal molecule in the current study, but it is a surrogate for a pathogen-modulating compound that would otherwise be held in abeyance in the vesicle in future studies.
E. coli alone does not respond to theophylline, and IPTG does not cross the vesicle membrane of the artificial cell in the absence of the pore. The ability of E. coli to receive the chemical message (IPTG) sent by the artificial cells was assessed in two ways.
First, a recombinant E. coli transformed with a plasmid, synthesized green fluorescent protein in response to IPTG; this was assayed using flow cytometry. Second, a natural or “wild type” E. coli was tested via reverse transcription quantitative polymerase chain reactions (RT-qPCR) that confirmed the up-regulation of the lac operon genes (more than a 20-fold increase).
The integration of artificial translator cells with natural cells represents a new strategy to introduce synthetic features to a biological system and at the same time, lessens the need for direct genetic manipulation...."
This event will feature important advances in synbio from leading companies in the field, ranging from industrial to healthcare applications. (RT @AmyElizaTayler: I'm going to the @IChemE SynBio symposium on 22nd Sept.