Chemical and genetic dissection of ABA receptor function

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Drought is the largest cause of crop losses in the United States and strategies to combat its effects are urgently needed. In order to improve drought tolerance in crops, we must understand the ways that non-domesticated plants naturally withstand drought. Plants respond to drought by producing a chemical signal called abscisic acid (ABA); its production relays information about drought from one part of the plant to another and ensures that protective responses occur. ABA gets its message across with the help of special proteins called receptors, which act like switches to turn on protective responses. For unknown reasons, plants have an unusually large number of these switches. The researcher hypothesizes that specific types of switches are more important for drought responses than others. Answering this hypothesis will have broad intellectual merit by illuminating the inner workings of plant cells. In addition, it will have important broader impacts, as it will help in breeding new drought tolerant crops. The researcher will test hypotheses, in part, using synthetic chemicals developed under previous NSF funding. These exciting new chemicals have enabled a partnership between the PI's lab and industry scientists, who seek develop chemicals that to mitigate the effects of drought on crop yield. The current proposal will characterize new chemicals and strengthen academia-industry relationships. This interdisciplinary project will strengthen the PI's deep commitment to mentoring students and post-doctoral scholars, and provide a unique training environment for plant biology, genetics, and chemistry.The researcher has made key contributions to understanding the function of the ABA receptors and in developing synthetic ABA-mimicking compounds. In spite of the tremendous progress made, our current understanding of ABA receptor function has been hampered by genetic redundancy. This proposal asks a simple question: why do plants need so many ABA receptors? In this proposal, the PI will define which receptors play a predominant role in modulating water relations and systematically dissect the roles of different receptors in mediating ABA's concentration-dependent effects. To do this the PI will employ a series of complementary chemical, genetic, and synthetic biological approaches. In one experimental approach, synthetic small molecules that activate either the high- or low-affinity receptors will be used to interrogate the roles of different receptors in distinct ABA responses. Small molecules are powerful probes of biological pathways but can be limited by "off-target" effects that can complicate interpretation of data. To address this limitation, the PI will also use synthetic biological strategies and engineer receptors that can be selectively controlled by a non-natural chemical. The likelihood of structurally unrelated molecules having identical off-target effects is low, therefore this strategy complements the first strategy. Lastly, genome editing will be coupled with classical genetic approaches to generate sets of plants that lack the different receptor subtypes. These materials will be characterized along with the other materials to build an integrated and systematic understanding of the functions of the ABA receptor family.