New Biosensor Methodology Lights the Way for Advances in Plant, Animal, and Human Sciences

Achievement date: 
2016
Outcome/accomplishment: 

With support from the NSF-funded Synthetic Biology Engineering Research Center (Synberc), headquartered at the University of California (UC) Berkeley, researchers at Harvard’s Wyss Institute and Harvard Medical School (HMS) developed a new method for synthetically engineering a broad range of biosensors that can be programmed to detect and signal with fluorescent light targeted molecules in living yeast, plant, and animal cells. These new reprogramming capabilities open an entirely new realm in efforts to transform ordinary organisms into extraordinary living cellular devices.

Impact/benefits: 

Biosensors in living organisms, and biological molecules that can tell you about their environment, are extremely useful for a broad range of applications, including fuels, plastics, and pharmaceuticals. The new biosensor method developed by the Harvard team overcomes past limitations and adds the capability to work with eukaryotic cells—which are found in organisms ranging from fungi to people—lighting the way for a wide range of new opportunities to advance agriculture, healthcare, energy, and other important fields. For example: biosensors used in agricultural plants could show the condition of the soil or the presence of toxins or pests; in the medical field, they could be used to identify treatments for medical conditions such as inflammation or infection; and in the energy sustainability arena, they could enhance the production of biofuels.

Explanation/Background: 

Eukaryotic organisms are full of diverse hormones, making it challenging to sense and respond to a specific hormone of interest. To test their new method, the researchers experimentally engineered yeast, plant, and mammalian cells to contain customizable ligand-binding domains (LBDs), which are receptors for hormones and other types of small molecules. These LBDs are tailored so that they only bind and detect a specific molecule. A secondary “signal” component fused to the LBD can be programmed to emit fluorescence or regulate gene expression once it has bound to the target molecule. The components of this biosensor¾the LBD in combination with the fluorescent or genetic signal¾degrade and fade away if the target molecule is not identified.

The team not only demonstrated its novel methodology in plants but also described its efficacy in turning yeast and mammalian cells into precise biosensors, which one day could be leveraged for use in industries that rely on the productivity of yeast or livestock, or for use as medical sensors. Overall, the method is extremely tunable and portable, meaning it can be used in a wide variety of organisms to detect a broad range of small molecules. “It’s another great enabling capability that will undoubtedly advance the entire field of synthetic biology,” said Wyss Institute Director Donald Ingber.

This work was also supported by the U.S. Defense Threat Reduction Agency, the National Institutes of Health, and the Department of Energy.