Chemical Genetics in Dissecting Membrane Glycerolipid Functions

Chemical genetics has emerged as a powerful approach to dissect biological processes, based on the utilization of small molecules disturbing the function of specific target proteins. By analogy with classical genetics, 'reverse chemical genetics' refers to the utilization of drugs acting on a known target, enabling its functional characterization at the levels of the cells, tissues and organisms. Likewise, 'direct chemical genetics' refers to the utilization of a drug of unknown mode of action, but triggering a phenotype of interest. In that case, one has to identify the target(s) possibly blocked (or possibly activated) by the small molecule. This chapter illustrates both approaches, like the analysis of the elongation of fatty acids, the biosynthesis of galactoglycerolipids or the catabolism of phosphoglycerolipids by reverse chemical genetics or the study of the membrane glycerolipid remodeling triggered upon phosphate starvation, by direct chemical genetics.