Molecular mechanism of a toxin-antidote system

University Of Washington, Seattle WA

Investigators

Abstract

This project investigates the molecular mechanisms underlying the action of a genetic element in nematode worms that leads to reproductive isolation, an initial step in the evolution and origin of new species. This research will be complemented by the isolation and identification of new worm strains and species from nature by a large number of high school students, providing the raw material for future studies of related genetic elements. Students will benefit by learning how research is performed and will gain a basic understanding of genes, DNA, and evolution that is becoming increasingly more important and societally relevant. By engaging students in the practice of science, this project fulfills one of the three central dimensions in the Next Generation Science Standards recently adopted by many states across the nation to reform science education and will improve scientific literacy by helping to build an informed public that understands the scientific enterprise and can better contribute to future national policy decisions that require the interpretation and evaluation of scientific data. The project will also provide direct training in research for graduate, undergraduate, and high school students. This research focuses on investigating how a selfish genetic element consisting of a toxin and antidote acts at the cellular and molecular levels. The peel-1/zeel-1 system in the nematode C. elegans includes a toxin that kills cells unless counteracted by its antidote. This project aims to determine how the PEEL-1 toxin kills cells and how the ZEEL-1 antidote acts to prevent cell death. The project will test whether PEEL-1 kills cells by co-opting the small transmembrane protein PMPL-1 to form a toxic ion channel or membrane pore that leads to cell death due to osmotic dysregulation, and whether ZEEL-1 opposes this activity by facilitating the ubiquitylation and subsequent degradation of PEEL-1 or PMPL-1. The research will use C. elegans, HEK293T cells as a reconstituted heterologous system, and biochemical experiments using purified proteins. 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.