The small molecule abscisic acid (ABA) is an important hormone that regulates many aspects of plant growth and development and plays a critical role in plant response to environmental stress. As a stress hormone, ABA is a critical regulator of how plants cope with extreme changes in the environment such as droughts or unexpected freezes. Because of its importance during exposure to environmental extremes, the ABA response pathway has been reengineered by modern biotechnologists to create plants with improved yields under conditions of drought. Thus, research on the biology of ABA has had, and will continue to have, an impact on agriculture and human welfare. ABA, like many hormones, works by binding to receptors that turn on signaling pathways that ultimately control downstream physiological processes. Recent studies have identified three receptor proteins that bind ABA. The receptors identified to date all show strong exclusive preference for the natural form of ABA, but several studies have suggested the existence of undiscovered receptors that can bind to both natural and non-natural forms. A detailed understanding of how ABA is perceived is a major goal in plant biology and will require identifying all of the receptors that recognize ABA. The Principal Investigator's has discovered a family of 5 new proteins that are candidate receptors for both natural and non-natural ABA isomers. Because these are the first candidate proteins to interact with both natural and non-natural forms of ABA, the research should fill a current gap in our understanding of how ABA works in plants. The research project will use biochemical and molecular genetic approaches to understand the function of these proteins in plants. In addition, modern biological research requires training students to be confident moving between fields to solve problems. The investigator's lab engages in interdisciplinary research at the chemistry-biology interface and is an ideal environment for training scientists able to meet the challenges of modern scientific endeavors. The project will include activities focused on training undergraduate students and expose students to multidisciplinary research at the interface of chemistry and biology.
The recent 2012 drought was the most severe drought in the last half-decade and has had national and global economic consequences. The lack of sufficient water during a growth season is one of a number of adverse environmental conditions that scientists generally refer to as abiotic stresses; other abiotic stresses include high soil salinity, early freezes and flooding, to name a few. Given the devastating consequences that abiotic stresses can have on crop yields and prices, there is broad scientific interest in understanding the internal mechanism that plants use to cope with abiotic stresses so that these mechanisms can be modulated in crops to improve yield under adverse growth conditions. For example, as soil water levels decrease, plants produce increased levels of a hormone called abscisic acid (ABA). ABA limits water use by closing small pores on leaf surfaces (called stomata) and induces other physiological changes needed to cope with reduced water. The ability of ABA to mitigate the effects of drought has been known since the 1970’s, however the underlying molecular mechanism by which ABA elicits its effects was unclear when this NSF proposal was submitted. Most importantly, the site of ABA perception at a so-called receptor protein was not known. Given the critical importance of ABA as a plant stress hormone, many laboratories have actively sought the ABA receptor(s) but failed to identify candidates that stood up to close scrutiny. The PI’s NSF proposal was initiated in this context and was focused on identifying the cellular receptor(s) for ABA, an important goal since such proteins are critical for understanding ABA’s signaling pathway and for improving stress tolerance in crops. The PI's proposal was built around his laboratory’s discovery of a chemical called pyrabactin, a synthetic compound that activates ABA signaling in seeds by mimicking the action of ABA, analogously to the way synthetic steroids can mimic the effects of natural steroids in humans. Using this synthetic compound the PI discovered a gene called PYR1 (Pyrabactin Resistance 1) that was needed for pyrabactin to activate ABA signaling. Given the ability of pyrabactin to mimic ABA's effects, the PI hypothesized that ABA’s perception machinery was being hijacked by pyrabactin to elicit its effects and that PYR1 was likely to encode a protein directly involved in ABA perception (i.e. the long-sought ABA receptor). The major aim of the PI's proposal was therefore to conduct experiments that would determine if PYR1 was indeed an ABA receptor protein. Work conducted in the first 18 months of the funded time period established that the PI's hypothesis was correct and led to a significant breakthrough that was acknowledged as a runner-up for the 2009 'Breakthrough of the Year' list compiled by the journal Science. The PI’s NSF-funded discovery spawned a flood of collaborative papers (17 in total) on the mechanism of receptor function. In addition, the discovery is enabling new approaches for managing drought tolerance in crops; these approaches are underpinned by four receptor-technology patent applications filed by the University of California, the PI’s host institution. The PI’s laboratory is using these technologies to develop stress-modulating agrichemicals and genes in collaborative efforts with the agricultural company Syngenta Biotechnology. The PI’s NSF-funded activities have had broad impact and substantial intellectual merit. Prior to the PI’s work, ABA’s signaling system was composed of several pieces whose integration with one another was unclear; the understanding of how ABA receptors control the newly described core pathway has clarified this picture and provided a new framework for ABA’s signaling mechanism. The PI’s work has led to rewrites of textbook chapters on ABA, an important demonstration of the intellectual merit and impact of the work. The identification of ABA receptors has created new directions in plant biotechnology, which provides evidence of the broader impact of the work in the context of agriculture.
