The control of lipid homeostasis is a fundamental process that allows cells to maintain the unique lipid composition of their membrane compartments and to deal with the energetic fluxes from metabolism. If most of enzymes involved in lipid metabolism are characterized, the question of the genetic control of lipid homeostasis is still outstanding. In order to find genes that control the homeostasis of membrane lipids, I combined a large-scale RNAi screen targeting the human knome with the techniques of targeted lipidomic analysis by mass spectrometry to monitor lipid changes in HeLa cells. Data analysis of the screen allowed the characterization of candidate genes involved in the control of membrane lipid homeostasis. In parallel, in the context of the NCCR Chemical Biology, I developed a robotically-assisted siRNA transfection assay and screened a library of chemicals potentially able to transfect siRNA in Human cells at least as efficiently than commercially available compounds.