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Keasling, Carothers and their co-authors focused theirdesign-driven approach on RNA sequences that can fold intocomplicated three dimensional shapes, called ribozymes andaptazymes. Like proteins, ribozymes and aptazymes can bindmetabolites, catalyze reactions and act to control gene expressionin bacteria, yeast and mammalian cells. Using mechanistic models ofbiochemical function and kinetic biophysical simulations of RNAfolding, ribozyme and aptazyme devices with quantitativelypredictable functions were assembled from components that werecharacterized in vitro, in vivo and in silico. The models anddesign strategy were then verified by constructing 28 geneticexpression devices for the Escherichia coli bacterium. When tested,these devices showed excellent agreement - 94-percent correlation -between predicted and measured gene expression levels. "We needed to formulate models that would be sophisticated enoughto capture the details required for simulating system functions,but simple enough to be framed in terms of measurable and tunablecomponent characteristics or design variables," Carothers says. "Wethink of design variables as the parts of the system that can bepredictably modified, in the same way that a chemical engineermight tune the operation of a chemical plant by turning knobs thatcontrol fluid flow through valves. In our case, knob-turns arerepresented by specific kinetic terms for RNA folding and ribozymecatalysis, and our models are needed to tell us how a combinationof these knob-turns will affect overall system function." JBEI researchers are now using their RNA CAD-type models andsimulations as well as the ribozyme and aptazyme devices theyconstructed to help them engineer metabolic pathways that willincrease microbial fuel production. JBEI is one of three DOEBioenergy Research Centers established by DOE's Office of Scienceto advance the technology for the commercial production of clean,green and renewable biofuels. A key to JBEI's success will be theengineering of microbes that can digest lignocellulosic biomass andsynthesize from the sugars transportation fuels that can replacegasoline, diesel and jet fuels in today's engines. "In addition to advanced biofuels, we're also looking intoengineering microbes to produce chemicals from renewable feedstocksthat are difficult to produce cheaply and in high yield usingtraditional organic chemistry technology," Carothers says. While the RNA models and simulations developed at JBEI to date fallshort of being a full-fledged RNA CAD platform, Keasling, Carothersand their coauthors are moving towards that goal. "We are also actively trying to make our models and simulationsmore accessible to researchers who may not want to become RNAcontrol system experts but would nonetheless like to use ourapproach and RNA devices in their own work," Carothers says. While the work at JBEI focused on E. coli and the microbial production of advanced biofuels, the authors ofthe Science paper believe that their concepts could also be usedfor programming function into mammalian systems and cells. "We recently initiated a research project to investigate how we canuse our approach to engineer RNA-based genetic control systems thatwill increase the safety and efficacy of regenerative medicinetherapies that use cultured stem cells to treat diseases such as diabetes and Parkinson's," Carothers says. This research was supported in part by grants from the DOE Officeof Science through JBEI, and the National Science Foundationthrough the Synthetic Biology Engineering Research Center(SynBERC). Additional References Citations. I am an expert from led-torchflashlight.com, while we provides the quality product, such as AAA LED Flashlight , LED Rechargeable Flashlight, Mini LED Flashlights,and more.
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