Advanced bioengineering of plant hormone receptors may lead to controlling complex genetic circuits in living cells, according to new research by Associate Professor Timothy Whitehead and his partners. Their paper, “Plant hormone receptors as reprogrammable scaffolds for rapid biosensor development," was recently published in Nature Biotechnology.
The group repurposed the natural functions of a plant hormone receptor to sense and respond to agrochemicals, synthetic drugs and pesticides. They also showed these biosensors could function in a variety of sense-response platforms in living cells or in laboratory-based assays using purified components.
“We think such biosensors that can control life processes can be made for nearly all drug-like compounds,” Whitehead said.
This research may result in a variety of long-term applications, including developing engineered living systems in plants and microorganisms that monitor environmental contaminants, as well as precision cellular biotherapies wherein the biologically active material can be activated or deactivated via the deployment of small molecules.
“There is a tremendous technology on antibody engineering where one can develop an antibody for nearly any other protein or larger biomacromolecule,” Whitehead said. “However, no such technology exists for small molecules. We wanted to create a broad technology platform that one can use to identify small molecule biosensors for nearly any molecule.”
The researchers’ biosensors can detect contaminants such as organophosphate pesticides, as well as nearly two dozen natural and synthetic cannabinoids that can be used for rapid toxicology screening. While this research was not conducted on plants directly, the researchers believe that using plant proteins in their platform will facilitate the rapid creation of future plant-based sensors.
“This collaborative team, funded through our Molecular Foundations for Biotechnology initiative, reached a key milestone by bringing together molecular modeling, X-ray crystallography and structure-guided, fine-tuned directed evolution to develop novel sensors for high value molecules,” said David Berkowitz and Jeanne VanBriesen, the directors of NSF Division of Chemistry and Division of Chemical, Bioengineering, Environmental and Transport Systems, respectively, in a joint statement. “This has the potential to significantly expand our ability to analyze many different chemical structures, from drugs like opioids, to pesticides like organophosphates. The work highlights the power of convergent research to solve problems that span traditional scientific disciplines.”
Whitehead cited the contributions of CU Boulder co-first authors and postdoctoral associates PJ Steiner and Matt Bedewitz who helped develop the overall concept and technology, as well as Department of Chemical and Biological Engineering graduate students and NSF GFRP award winners Zach Baumer and Alison Leonard for conducting essential control experiments.
This research was funded by the Defense Advanced Research Projects Agency, the National Science Foundation and the National Institute of Health as part of a collaboration with the Donald Danforth Plant Science Center to support the DARPA Advanced Plant Technologies (APT) program. It included collaboration with Jesus Beltran, Sean Cutler, Shuang Wei and Ian Wheeldon of the University of California Riverside, as well as researchers from the Medical College of Wisconsin, Michigan State University and the Donald Danforth Plant Science Center.