Gene expression profiling, a revolutionary tool in Bayer CropScience herbicide discovery

摘要

With about US 13 billion dollar in turnover, the herbicide market is by far the biggest segment in the plant protection market. Over the last 10 years, it has grown only moderately because market dynamics were basically driven by replacement of established products with new herbicides showing only slightly better properties. Now the industry is researching novel solutions with superior agronomic profiles: profiles, which could alter the market-landscape or which even could create new market segments.Identification of compounds with novel herbicidal Modes of Action (MoA) would have the potential to open new segments and to trigger more growth. Therefore it is mandatory to exclude candidates with unfavourable MoAs very early from the research processand to concentrate the research efforts on compounds with favourable or even novel MoAs.Gene Expression Profiling (GEP) with DNA microarrays (chips) is a new technology used to measure changes in the entire transcriptome, i.e. full complement of active genes, of an organism in a single experiment. We have used GEP to create a catalogue of genetic fingerprints of the plant Arabidopsis thaliana, each fingerprint being characteristic for a single herbicidal MoA. We use this catalogue to rapidly classify herbicidal compounds from our Ultra High Throughput Vivo Screening (UHTVS) according to their MoA. Besides classification of herbicidal compounds into known MoAs, GEP also provides the opportunity to identify the affected metabolic pathway in the plant. Determination of the affected pathway is a first step towards the identification of novelherbicidal targets. Additionally GEP can identify the MoA of pro-drugs, which cannot be elucidated by conventional biochemical methods. GEP provides insight into the interactions of any herbicidal compound with the entire plant metabolism with unprecedented accuracy and completeness. Gene Expression Profiling is now used routinely in Bayer CropScience research and has become an indispensable tool for our herbicide discovery process.