EAGER: Stress resistance pathways in C. elegans

Harvard University, Cambridge MA

Investigators

Abstract

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5). In the nematode C. elegans, experimentally introduced double-stranded RNA (dsRNA) mediates specific gene silencing that spreads between cells and tissues of the animal (and can even be transmitted to progeny). This remarkable spreading phenomenon is known as systemic RNA interference (RNAi), and is facilitated by a channel protein called SID-1 that transports double-stranded RNA (dsRNA) between cells. Although SID-1 homologs exist in numerous species, including all vertebrates and many invertebrates, an endogenous role for systemic RNAi in general and SID-1 in particular remains unknown. The overall goal of this research project is to uncover a physiological and/or developmental role for SID-1 and systemic RNAi in C. elegans. This project will test the hypothesis that SID-1 protects animals against environmental stress by coordinating communication between cells via stress-related noncoding RNAs (ncRNAs). In doing so, the research will take advantage of the wealth of existing genetic resources (e.g. mutant collections) and techniques (e.g. RNA profiling, in situ hybridizations, transcriptional reporters) available in C. elegans. Intellectual merit: This project seeks to make novel and transformative advances that have the potential to uncover a likely widespread means of RNA-mediated, cell-to-cell communication that can span generations. Given the burgeoning interest and investment in both basic and applied aspects of the RNAi pathway, the research is especially timely. The research has the potential to provide important new insights into the functions of endogenous dsRNA in animals, as novel messengers that transmit stress signals throughout the organism. Broader impacts: The planned activities will advance the goals of the NSF in four ways, namely by: 1) Teaching and training of undergraduate students and postdoctoral fellows; 2) Broadening the scientific participation of underrepresented groups; 3) Disseminating scientific and technological findings through publication; and 4) Providing specific benefits to society, including knowledge that will advance the development of the therapeutic application of RNAi to treat genetic and acquired diseases.