EAGER: New insights into the biology of cell transdifferentiation

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The ultimate goal of regenerative research is to replace damaged cells in response to injuries and aging. Transdifferentiation (or cell reprogramming), a process through which a mature somatic cell transforms into a new type of mature somatic cell, can achieve this goal. The mechanisms by which cells spontaneously (in vivo) leave a differentiated state to become a new lineage are poorly understood. This is due to the difficulties in inducing transdifferentiation in live model systems. A new promising approach comes from the cnidarian Turritopsis dohrnii. Most animals reproduce, age, and die. T. dohrnii has escaped this fate. When faced with unfavorable circumstances, the jellyfish of T. dohrnii avoid death by reverting to a younger life cycle stage, the polyp. During the life cycle reversal, which covers a time span of about 24 hours, cell transdifferentiation occurs. These characteristics make T. dohrnii a potential new system for in vivo research on the molecular mechanisms of cell stability and transdifferentiation. This project will produce genomic tools and assess the potential of T. dohrnii as a system for the study of in vivo cellular differentiation. The research has three objectives: 1) Produce transcriptome assembly and annotation of T. dohrnii. 2) Produce a hybrid draft genome assembly and annotation of T. dohrnii. 3) Conduct differential gene expression analyses of life cycle stages of T. dohrnii. The genomic tools (draft genome and transcriptome assembly) will be crucial steps toward facilitating the development of genome editing tools. The differential gene expression analyses will provide insight on the specific genes that are associated with the mechanisms of cellular transdifferentiation that occur during the reverse development of T. dohrnii. This project supports outreach activities and the creation of a portal that will contain information, up to date research, useful links to scientific literature, pictures, and a high-definition video of T. dohrnii's life cycle reversal. With numerous unscientific and inaccurate websites on "the immortal jellyfish" these activities aim to populate the Internet with reliable information and visual products on T. dohrnii.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.