High-Content Screening in Forward (Phenotypic Screening with Organisms) and Reverse (Structural Screening by NMR) Chemical Genetics

Abstract

High-content screening (HCS) aims not only to isolate molecules that are active towards a biological target but also to obtain the maximum amount of information during the screening about the effect of the molecule on this target. Here the notion of ‘biological target’ covers both molecularly defined biomolecules and complex biological systems. When the targets are identified molecularly, the effects of the targeted molecules can be studied on the isolated target in vitro (structural screening in parallel) or on the target in its cellular context, in vivo. These are procedures in reverse chemical genetics (chapter 8). It is also possible to search for molecules active on metabolic or signalling pathways without any molecular characterisation of the target. Phenotypic screening with cells or whole organisms are approaches in forward chemical genetics (chapter 8).