EDGE CT: Catalyzing regeneration research by developing functional tools for post-embryonic stages

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Injury is widespread in nature and animals possess varied mechanisms to cope with damage or the loss of body parts. One of the most dramatic injury responses known is regeneration, the regrowing of a body part that has been lost. Although this ability is quite limited in some animals, such as mammals, many others are able to regenerate extensive parts of their body. Technical challenges have severely limited the study of the genes involved in regeneration in some of the most highly regenerative animals. Annelids, or segmented worms, include numerous highly regenerative species but there are no robust approaches for studying the genetic basis of regeneration in this group. The team of investigators of this project develop new approaches for testing the function of genes during regeneration in three highly regenerative annelid species. This work will open up the possibility of identifying the genes and molecular pathways responsible for the remarkable regenerative abilities of annelid worms, and is expected to help catalyze research in other groups of animals. Technical advances are shared broadly with relevant research communities through roundtable discussions at scientific conferences, a laboratory-based hands-on workshop, a project blog, and other online forums. The team of investigators also develop and disseminate general educational resources about regeneration and its study, including an educational comic book and teaching materials for high school science teachers and students. This project addresses a central technical challenge for studying regeneration in many animal groups: manipulating gene function in post-embryonic life-history stages. The project is executed by a close-knit team of researchers and focuses on developing functional approaches to interrogate the genotype-phenotype relationship in three focal annelid species with distinct life histories and adult growth patterns: Platynereis, Capitella, and Pristina. In Aim 1, post-embryonic delivery techniques are optimized using a combination of injection and electroporation. In Aim 2, knock-down approaches using morpholinos and siRNAs in post-embryonic stages are developed, and in Aim 3, gene knock-ins and knock-outs in post-embryonic stages using CRSPR/Cas9 are developed. The work is expected to have a strong catalyzing effect on research, with an increase in the power of inquiry in these other soft-bodied and vermiform animals for existing research labs, an increase in the number of research labs utilizing such organisms and tools.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.