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
Abstract:
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.