FIGURE 1: Exacerbate-reverse as an approach to identify genes and drugs to target and treat LSDs. The general outline of the approach (dark grey) starts with using genome-wide analyses in yeast to identify gene mutants that exacerbate the phenotype that mimics the human disease, followed by analyses of mammalian orthologs that can ultimately be targeted with drugs to reverse the disease phenotype. The original use of the approach investigating LSDs started with the yeast model of NP-C disease (light grey) and culminated in the identification of Vorinostat as a candidate therapy that is now in clinical trial. Dilutions of yeast cells were grown in aerobic (normal) and anaerobic (sterol auxotrophy) conditions. The NP-C patient fibroblasts were stained with filipin, a diagnostic marker of cholesterol accumulation. The Npc1^nmf164 mouse liver cells were stained with hematoxylin/eosin (H/E), to distinguish lipid-laden cells (blue) from healthy hepatocytes (red). Originally published in [14]; © the American Society for Biochemistry and Molecular Biology.

14. Starovoytova AN, Sorokin MI, Sokolov SS, Severin FF, and Knorre DA (2013). Mitochondrial signaling in Saccharomyces cerevisiae pseudohyphae formation induced by butanol. FEMS Yeast Res 13(4): 367–374. https://doi.org/10.1111/1567-1364.12039