Project Summary/Abstract: Overview of research: Research in my lab centers on marine regenerative biology and specifically on stem cell-mediated regeneration. Our research organism is the hydrozoan cnidarian Hydractinia symbiolongicarpus. Hydractinia is a colonial invertebrate that has evolved a remarkable stem cell system and an astonishing capacity for regeneration. This animal can regenerate all of its tissues throughout life, owing to the constant turnover of its migratory stem cells, known as i-cells. The i-cell population is functionally heterogeneous and recently, fast-cycling and slow-cycling ‘quiescent’ sub-populations of i-cells have been identified based on cell cycle characteristics. Together with collaborators, we recently sequenced and assembled the Hydractinia genome and have created fluorescent transgenic lines. The genomic resources we have created and the functional molecular tools that currently exist and are under development for gene loss- and gain-of-function experimentation are enabling a new era of Hydractinia research. Goals for next five years: Our first goal is to successfully isolate purified sub-populations of stem cells from Hydractinia. Once this is achieved, we will work to characterize the essential nature of the i-cell sub- populations using global single cell transcriptional profiling (single cell RNAseq), followed by careful functional genetic experimentation. We will aim to characterize the underlying mechanisms governing i-cell maintenance during homeostasis and deployment during regeneration. Overall vision: My overall vision is to significantly contribute to the field of regenerative medicine by establishing Hydractinia as an exciting new research organism for stem cell and regeneration research. Hydractinia has a combination of traits such as small size, transparency, short generation times, and easy access to embryos that make it ideal for model organism development. As one of a handful of highly regenerative animals that can be easily cultured, spawned, and manipulated in the lab, Hydractinia is poised to help us unlock the mysteries and mechanisms that govern stem cell quiescence and proliferation. Our studies will characterize stem cell function in the contexts of normal tissue homeostasis and throughout the diverse molecular and cellular events of regeneration. One major long-term goal is to provide a means to specifically target and activate quiescent stem cells in vivo to enhance tissue regeneration that may ultimately be applied to human cells.