Quantitative Biology / Gene Expression in Development & Disease Seminar

Friday, 22 March 2013 at 11:30am

Room 1400 Biomedical and Physical Sciences Bldg.

Refreshments at 11:30

Speaker:  Ethan Perlstein, Lewis-Sigler Institute for Integrative Genomics, Princeton University

Title:  Do Yeast Get Depressed? Tales of an Evolutionary Pharmacologist

My research interests are in evolutionary pharmacology, the study of complex drugs using simple genetic model organisms. For 5 years at Princeton, my lab used cellular drug responses of the budding yeast Saccharomyces cerevisiae as a model for psychopharmacology. A recurring theme of our work is that cell membranes are a novel drug target of basic and hydrophobic psychoactive drugs, such as antidepressants, antipsychotics and antihistamines. Using a radioactive version of the antidepressant Zoloft, we identified several evolutionarily conserved cellular pathways, including autophagy, that modify drug accumulation both in yeast cells and a rat neuronal cell line (PC12). These pathways regulate the shape and function of specific cell membranes that comprise acidic organelles of the secretory and endocytic pathways, as revealed by quantitative, bilayer-resolution electron microscopy. The accumulation of cationic amphipathic drugs in cell membranes has a cytoprotective effect in yeast mutants with altered clathrin function, a striking observation that has implications for the unexplained neurogenic effects of antidepressants in people. Finally, last Fall I and my team of collaborators crowdfunded over $25,000 for a project to examine the distribution of radioactive amphetamines in the mouse brain. In the spirit of Open Science, we are sharing data in real-time and proactively engaging with the public.