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Discovery of small molecules that alter plant traits in a beneficial manner


The goal of University of California Riverside’s Center for Plant Cell Biology Chemical Genomics Interdisciplinary Graduate Research and Training (ChemGen IGERT) program, funded by the National Science Foundation (NSF), is to foster productive interactions between biologists, chemists, computer scientists and engineers across traditional disciplinary boundaries. To achieve this, 19 fellows and 4 associates of the ChemGen IGERT program actively research plant and plant pest/pathogen biology using chemical genomics as a tool. Chemical genomics is the systematic discovery of drugs that affect specific biological processes using model organisms. Implementation of this approach requires orchestrated research initiatives in genetics, biochemistry, synthetic organic chemistry, analytical chemistry, computation biology, and bioengineering. The research project of each ChemGen IGERT participant involves at least two of the target disciplines, Biology, Chemistry, Computer Sciences and Engineering, to provide significant exposure to the technologically innovative field of chemical biology.

Address Goals

The following description is an exemplary research project that involves ChemGen IGERT PhD students and faculty from multiple disciplines.

Discovery of novel synthetic elicitors of plant immune responses as leads for new pesticides and tools for the dissection of the plant defense network. A collaborative ChemGen project has been the identification and characterization of compounds that activate cellular pathways that provide defense to pathogens. The recognition of small bioactive molecules that can be applied to plants to trigger these distinct disease resistance pathways can lead to better and safer pesticides for public and commercial use. This project is led by Assistant Professor Thomas Eulgem of the Center for Plant Cell Biology. ChemGen IGERT fellows Colleen Knoth and Melinda Salus identified compounds from the ~50,000 compound library purchased with IGERT funds that activate plant defense responses. Of 42,000 diverse compounds, Knoth and Salus identified 114 candidate elicitors triggering expression of the defense marker gene CaBP22. One of the identified compounds, 3,5-Dichloroanthranillic acid (DCA), studied in detail, provides protection from infection by the oomycete Hyaloperonospora parasitica and the bacterium Pseudomonas syringae partially by activating unknown defense mechanisms. Application of DCA to uninfected plants provides temporal immunity in several species. Using DNA microarrays, groups of plant genes were recognized that are significantly up or down-regulated after application of DCA. Salus has shown that mutants in some of these genes have abnormal levels of pathogen growth, indicating the usefulness of this compound to identify additional components in the plant defense network. Salus is performing screens to identify additional compounds that influence other aspects of plant defense responses. Complementary to this project, ChemGen IGERT fellow Paul Xu, an organic chemist, is working with Pirrung and Eulgem on a compound produced by the plant pathogen Pseudomonas syringae, Syringolin A (SylA). SylA is a proteasome inhibitor, which has anti proliferation effects on both neuroblastoma and ovarian cancer cells. In addition, SylA also induces plant defense against powdery mildew in rice and wheat. Xu’s main goal is to synthesize and develop SylA derivatives that particularly efficiently and specifically induce plant defense responses. Analogous to the work on DCA, these SylA derivatives will be used as tools to dissect plant defense signaling and may serve as leads for the design of novel pesticides.

The investigation of compounds associated with plant defense responses combines student training in biology, analytical and organic chemistry and bioinformatics. Four faculty members are involved (Eulgem, Girke, Pirrung and Larive). The project has included participation of NSF-Research Experience for Undergraduates students (Jonathan Ringler and Jon Tracey) and UCR undergraduates (Arif Mosavi and Heidi Sanchez) and enabled Eulgem to recruit a USDA grant on novel plant defense elicitors (USDA CSREES grant 2008-35301-19264). Publications and Patents: Knoth C, Ringler J, Dangl J, Eulgem T (2007) Arabidopsis WRKY70 is required for full RPP4-mediated disease resistance and basal defense against Hyaloperonospora parasitica. Molecular Plant Microbe Interactions 20(2):120-128.

Knoth, C., Eulgem, T. 2008. The oomycete response gene LURP1 is required for defense against Hyaloperonsopora parasitica in Arabidopsis thaliana. Plant J. 2008 Jul; 55(1):53-64.

Knoth. C., Salus, M., Girke, T., Eulgem, T. (2009) The synthetic elicitor 3,5-Dichloroanthranillic acid (DCA) induces NPR1-dependent and NPR1-independent mechanisms of disease resistance in Arabidopsis thaliana. Plant Physiology. 2009 Mar 20. [Epub ahead of print]

The synthetic elicitor DCA is covered by a provisional patent by Colleen Marie Knoth et al. (Application No: 61/083,154).