ChemicalGenomicsApproachesinPlantBiology

Chemical genomics (i.e., genomics-scale chemical genetics) approaches are based on the ability of low-molecular-mass molecules to modify biological processes. Such molecules are used to affect the activity of a protein or a pathway in a manner that is tunable and reversible. A major advantage of this approach compared to classical plant genetics is the fact that chemical genomics can address loss-of-function lethality and redundancy. Bioactive chemicals resulting from forward or reverse chemical screens can be useful in understanding and dissecting complex biological processes due to the essentially limitless variation in structure and activities inherent in chemical space. An important aspect of utilizing small molecules effectively is to characterize bioactive chemicals in detail including an understanding of structure activity relationships (SARs) and the identification of active and inactive analogs. Bioactive chemicals can be useful as reagents to probe biological pathways directly. However, the identification of cognate targets and their pathways is also informative and can be achieved by screens for genetic resistance or hypersensitivity in Arabidopsis thaliana or other organisms in which the results can be translated to plants. Here, we describe approaches to screen for bioactive chemicals that affect biological processes in Arabidopsis. We will also discuss considerations for the characterization of bioactive compounds and genetic screens for target identification. This should provide those who are considering this approach some practical knowledge of how to design and establish a chemical genomics screen.