Ecophysiology of chemical defense evolution in poison frogs

Stanford University, Stanford CA

Investigators

Abstract

Many organisms, including humans, are exposed to a variety of compounds in the diet that may result in toxicity. In nature, some animals have specialized physiology that allow them to ingest toxins without being harmed. Some Central and South American poison frogs can sequester neurotoxins in their diet and repurpose those toxins as a chemical defense from predation. These frogs move the alkaloids from the intestines, through the bloodstream and to the skin where toxins are stored in glands. This project investigates how these frogs cope with ingesting neurotoxins and the results may provide a more complete picture of oral drug distribution, metabolism, and new methods of toxin resistance, because many of the toxins are similar to pharmaceutical drugs used in humans. This research will provide learning experiences to all age groups in both the United States and Ecuador, where research and fieldwork on poison frogs is conducted. High school biology teachers will be involved in summer research and will incorporate their research findings into their science curriculum. This award will also provide research internships for local community college students, and a portion of this research will be conducted in an undergraduate laboratory course at Stanford University. In Ecuador, research will be communicated to the public through educational displays at the Centro Jambatu of Amphibian Research and Conservation in Quito. Poison frogs acquire alkaloid-based chemical defenses from dietary arthropods, although how these lipophilic alkaloids are moved across organs without self-toxicity is unclear. The goal of the proposed research is to understand the physiological mechanisms and convergent evolution of toxin sequestration and autoresistence in poison frogs through three aims: (1) Test the hypothesis that independent evolutionary origins of chemical defense is associated with expression changes of genes whose products are involved in small molecule transport and metabolism. Alkaloid profiles and gene expression in several tissues will be quantified across poison frog species that represent independent origins of chemical defense evolution. (2) Test the hypothesis that alkaloid sequestration evolved by co-opting transporter proteins for either sequestration or excretion. Gene expression profiling across organs in toxic and non-toxic lab-reared poison frogs will be used to identify membrane transporters enriched in tissues that sequester alkaloids. Candidate carriers will be functionally tested in cell-based assays. (3) A serpin protein in poison frogs that can bind a range of alkaloids was recently discovered by the research team. The binding profile of this toxin sponge for various alkaloids will be examined. Whether this toxin sponge is necessary for alkaloid sequestration will be tested through gene knockdown studies. Together, this work will test the hypothesis that chemical defense in poison frogs evolved via multiple mechanisms, each of which occur at a distinct level of organismal organization. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.