Growth and Development of higher plants

Chemical genetics is an approach in which a collection of small molecules is used to dissect biological processes in cells or whole organisms. We can distinguish between two different chemical genetic strategies. In the phenotype-based approach, a chemical library with 10,000 or more compounds is assembled. Subsequently, a high-throughput screen is performed to identify compounds that affect a biological process of interest. As a final step, the protein targets of these compounds are identified. The second approach (target-based) entails over-expressing a protein of interest, screening for compounds that interact with the protein and finally using this compound to determine the phenotypic consequences of altering the function of this protein in a cellular context.
To perform a chemical genetic screen, three important tools are required. First, a chemical library with 10,000 or more compounds is required. At the department of Plant Systems Biology, we have the DIVERSet chemical library from ChemBridge Corporation available. It is a pre-designed collection of 10,000 drug-like small molecules. The compounds are rationally selected based on 3D pharmacophore analysis to cover a broad range of biologically relevant pharmacophore diversity space. The second tool is a robust biological assay that is down-scalable to a 96-well plate format to study a biological process in a model system. Possible model systems include cell-free or cellular systems or even small model organisms such as Arabidopsis thaliana. And finally, to study the effect of a large number of compounds on the model system, there is need for a screening platform. At the department of Plant Systems Biology, we have a high-throughput screening platform available to automatically add the compounds to the assay system and to read-out the exerted effects with plate readers or microscopes.