Considerations for designing chemical screening strategies in plant biology

Traditionally, biologists regularly used classical genetic approaches to characterize and dissect plant processes. However, this strategy is often impaired by redundancy, lethality or pleiotropy of gene functions, which prevent the isolation of viable mutants. The chemical genetic approach has been recognized as an alternative experimental strategy, which has the potential to circumvent these problems. It relies on the capacity of small molecules to modify biological processes by specific binding to protein target(s), thereby conditionally modifying protein function(s), which phenotypically resemble mutation(s) of the encoding gene(s). A successful chemical screening campaign comprises three equally important elements: (1) a reliable, robust, and quantitative bioassay, which allows to distinguish between potent and less potent compounds, (2) a rigorous validation process for candidate compounds to establish their selectivity, and (3) an experimental strategy for elucidating a compound's mode of action and molecular target. In this review we will discuss details of this general strategy and additional aspects that deserve consideration in order to take full advantage of the power provided by the chemical approach to plant biology. In addition, we will highlight some success stories of recent chemical screenings in plant systems, which may serve as teaching examples for the implementation of future chemical biology projects.