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Advancing Research in Plan Cell Biology through Chemical Genomics Projects that Provide Student Training Across Disciplinary Boundaries of Chemistry, Computer Science, Engineering and Biology
Achievement/Results
The major goal of University of California Riverside’s Center for Plant Cell Biology Chemical Genomics Interdisciplinary Graduate Research and Training (ChemGen IGERT) program is to foster productive interactions between biologists, chemists, computer scientists and engineers. A major challenge to biologists is the successful bridging across traditional disciplinary boundaries. To achieve this, the research of the fifteen current ChemGen IGERT fellows focuses on the use of chemical genomics to further knowledge of plant and plant pathogen biology. Chemical genomics is a systematic approach involving the discovery of drugs that affect specific biological processes. Implementation of this approach requires orchestrated research initiatives in genetics, biochemistry, synthetic organic chemistry, analytical chemistry, computation biology, biochemical and mechanical engineering. A primary objective is to culture graduate research projects that involve at least two of the target disciplines and to provide students will significant exposure to chemical biology.
The following three descriptions are exemplary research projects of ChemGen IGERT fellows.
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 NSF ChemGen IGERT-sponsored study led to the characterization of compounds that activate cellular pathways that provide defense to pathogens. This project is lead by Assistant Professor Thomas Eulgem of the Center for Plant Cell Biology. ChemGen IGERT fellows Colleen Knoth and Melinda Salus have identified compounds from the ~50,000 compound library purchased with IGERT funds that activate plant defense responses. Of 42,000 tested library compounds, Knoth and Salus identified 114 candidate elicitors triggering expression of the defense marker gene CaBP22. One of the identified compounds, studied in detail, provides protection from infection by the oomycete Hyaloperonospora parasitica and the bacterium Pseudomonas syringae. Application of this compound to uninfected plants provides temporal immunity in Arabidopsis and tomato. Salus is performing screens to identify additional compounds that influence defense responses. This project involves student training in biology, chemistry and chemi-informatics. The project included participation of NSF-Research Experience for Undergraduates (NSF-REU) students (Jonathan Ringler and Jon Tracey). Bioinformatic and chemi-informatic components of Knoth’s project are under the supervision of bioinformaticist Assistant Professor Thomas Girke. Consultation in chemistry for Salus is provided by synthetic organic chemist Professor Michael Pirrung and analytical chemist Professor Cynthia Larive.
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. The Plant Journal. In the press.
(3) Characterization of transcriptomic and metabolmic adjustment of plants to external stimuli. A multi-faceted analytical pipeline was developed to dissect the complex metabolic responses to environmental and chemical stress in the flowering plant Arabidopsis thaliana, a member of the mustard family closely related to cauliflower, cabbage and broccoli. This project employs chemistry, multivariate statistics, computer science, bioinformatics, plant biology and biochemistry to examine and interpret the complex metabolic response to stress. This project involves two ChemGen IGERT students (Kayla Kaiser (nee Hamersky), PhD student in Chemistry and Charles Jang, PhD student in Bioinformatics). Their goal has been to establish unified high throughput methods for the analysis of adjustments of Arabidopsis to environmental stimuli. In experiments performed under the direction of biologist Julia Bailey-Serres and analytical chemist Cynthia Larive, Jang and Kaiser have analyzed the coordination of dynamic responses to oxygen deprivation and reoxygenation. Kaiser established new methods for quantitative analysis of metabolites using proton nuclear magnetic spectroscopy. Jang performed statistical and computational evaluation of gene expression data derived from steady-state mRNA transcripts and polysome-associated mRNA transcripts. A submitted manuscript presents evidence of multiple levels of genetic control of plant response to environmental stimuli. Jang has screened over 40,000 compounds for molecules that inhibit the activity of mitogen-activated protein kinases (MPKs) and Kaiser is establishing genetic stocks of Arabidopsis with different sensitivity to herbicides that will be used to study metabolic responses to chemicals. Two under represented minority interns in our site NSF-REU programs worked under the direction of Kaiser and Jang in the summer of 2007 (chemist, Archie Taylor; http://research.chem.ucr.edu/groups/larive/reu/...) and plant biology (biologist, Daniel Swank; http://www.cepceb.ucr.edu/about/REUAd2008.html#...).
Address Goals
The ChemGen IGERT program fosters advanced research that addresses basic cellular processes and has potential implications in agriculture or biomedical research. The students are trained to be comfortable addressing research questions that span more than one academic discipline. These new practitioners of science should be able to excel in future research.
