Pioneering genomics researcher J. Craig Venter—best known for leading the privately funded team that sequenced the first human genome—will give a keynote talk at the University of Colorado Boulder on Sept. 29 about the scientific potential of and future products derived from “synthetic life.”
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...."
A synthetic biology project begun 13 years ago by Jay Keasling was culminated with the announcement that a microbial-based version of the antimalarial drug artemisinin has been shipped to African nations where it is most needed.
Plants are increasingly being used for the production of recombinant proteins. One reason is that plants are highly amenable for glycan engineering processes and allow the production of therapeutic proteins with increased efficacies due to optimized glycosylation profiles. Removal and insertion of glycosylation reactions by knock-out/knock-down approaches and introduction of glycosylation enzymes have paved the way for the humanization of the plant glycosylation pathway. The insertion of heterologous enzymes at exactly the right stage of the existing glycosylation pathway has turned out to be of utmost importance for optimal results. To enable such precise targeting chimeric enzymes have been constructed. In this short review we will exemplify the importance of correct targeting of glycosyltransferases, we will give an overview of the targeting mechanism of glycosyltransferases, describe chimeric enzymes used in plant N-glycosylation engineering and illustrate how plant glycoengineering builds on the tools offered by synthetic biology to construct such chimeric enzymes.
"Carotenoids are a class of diverse pigments with important biological roles such as light capture and antioxidative activities. Many novel carotenoids have been isolated from marine organisms to date and have shown various utilizations as nutraceuticals and pharmaceuticals. In this review, we summarize the pathways and enzymes of carotenoid synthesis and discuss various modifications of marine carotenoids. The advances in metabolic engineering and synthetic biology for carotenoid production are also reviewed, in hopes that this review will promote the exploration of marine carotenoid for their utilizations."
Stuart Bradford: Synthetic Biology. Stuart Bradford created a series of illustrations for Harvard Alumni magazine on synthetic biology, wherein scientists alter genetic structure to create tiny machines, tinkering like engineers.
"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."