Abstract
Infections due to parasitic nematodes result in nearly 125,000 deaths annually. Strikingly, this rate remains nearly unchanged in the past 50 years likely owing to the fact that treatment options are either inefficient or inaccessible. Prior to infecting humans, most parasitic nematodes begin as larvae where they feed nearly exclusively on bacteria. This unique property may offer an opportunity to develop new biological control agents with the use of synthetic biology. Recently, we have engineered a bacterium, consisting of an attraction module and toxin module that lures in and kills nematodes, respectively, using the principles of synthetic biology to act as biological control agent of the model nematode Caenorhabditis elegans. While independently characterizing of the two genetic modules governing the behavior of the engineered bacterium was successful, combining both modules in the same bacterial cell resulted in a reduction in attraction and killing efficacy. In this study we show that this reduction in efficacy is due to the ability of C. elegans to learn that our engineered bacterium is deadly. To circumvent learning, and thus increase efficacy, we dynamically regulate the modules of our engineered bacteria. We demonstrate that the order to activation of the modules is critical to successful attraction and killing of C. elegans. Our study paves the way for the engineering of autonomously regulated modules that may be optimized to be specific against diverse parasitic nematode species.
Faculty Sponsors
Robert Smith, Ph.D., Christopher Blanar, Ph.D., Evan Haskell, Ph.D.
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-10-2015 1:00 PM
End Date
4-10-2015 5:30 PM
Dynamic Regulation of Toxic Engineered Bacteria Prevents Learning in the Model Nematode Caenorhabditis elegans
Alvin Sherman Library
Infections due to parasitic nematodes result in nearly 125,000 deaths annually. Strikingly, this rate remains nearly unchanged in the past 50 years likely owing to the fact that treatment options are either inefficient or inaccessible. Prior to infecting humans, most parasitic nematodes begin as larvae where they feed nearly exclusively on bacteria. This unique property may offer an opportunity to develop new biological control agents with the use of synthetic biology. Recently, we have engineered a bacterium, consisting of an attraction module and toxin module that lures in and kills nematodes, respectively, using the principles of synthetic biology to act as biological control agent of the model nematode Caenorhabditis elegans. While independently characterizing of the two genetic modules governing the behavior of the engineered bacterium was successful, combining both modules in the same bacterial cell resulted in a reduction in attraction and killing efficacy. In this study we show that this reduction in efficacy is due to the ability of C. elegans to learn that our engineered bacterium is deadly. To circumvent learning, and thus increase efficacy, we dynamically regulate the modules of our engineered bacteria. We demonstrate that the order to activation of the modules is critical to successful attraction and killing of C. elegans. Our study paves the way for the engineering of autonomously regulated modules that may be optimized to be specific against diverse parasitic nematode species.
