RUI: Functional analysis of the exon junction complex in planarian stem cells and regeneration

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Non-Technical Paragraph: Many organisms, including humans, have some capacity to regenerate lost or damaged body parts following physical injury or disease. However, the extent of this ability varies considerably from one species to the next, and the biological mechanisms accounting for this variability are not well understood. This project will study genes that play a key role in the remarkable regenerative abilities of aquatic flatworms called planarians, animals that can re-form entire individuals from tiny body fragments in just over a week. Completion of the proposed objectives will advance our knowledge of how the large stem cell population that drives this process is regulated. Most research activities will be carried out by undergraduate students at Keene State College, providing valuable preparation for post-collegiate professional training and careers in the life sciences. Together with science outreach activities involving high school students, this will enhance New Hampshire's efforts to develop a technically proficient workforce crucial to further growth of the state's biotechnology and high-tech manufacturing industries.Technical Paragraph: This project will characterize post-transcriptional regulatory mechanisms governing gene expression in adult stem cells, using the planarian flatworm Schmidtea mediterranea as a model organism. Specifically, students will complete a functional analysis of the exon junction complex (EJC), a key regulator of RNA biochemistry with potentially conserved, yet poorly understood roles in stem cell biology. Prior work has established functions for the EJC in splicing, export of spliced mRNAs from the nucleus, translational control, and nonsense-mediated mRNA decay. The EJC has been linked to some gene-specific regulatory mechanisms during development; however, its biochemical function(s) and presumed RNA target(s) in self-renewing cell types in adult organisms are largely unknown. The research objectives of the current study will build upon preliminary data showing that the EJC is required for stem cell maintenance in planarians by: 1) Using RNAi and in situ hybridization to characterize the function and expression of EJC subunits during tissue homeostasis and regeneration; and 2) Combining candidate-gene and unbiased RNA-Seq approaches to identify EJC target RNAs. Completion of this research will enhance our understanding of molecular mechanisms governing gene expression in adult stem cells during tissue renewal and repair. The PI will undertake this work entirely with undergraduate and high school students to enhance STEM educational efforts in New Hampshire.