Project description
Planarian regeneration and nucleic acid modification
Flatworms are freshwater planarians with an extraordinary ability to regenerate lost body parts and a single stem cell from it can rescue a lethally irradiated organism. This ability is associated with the extreme plasticity of planarian stem cells (neoblasts). Preliminary studies indicated that the chemical modifications of the neoblast nucleic acids was a critical event that defines their homeostasis and regenerative ability. The EU-funded PLANMod project is applying an arsenal of modern functional gene analysis and molecular biology methods to establish basic mechanisms of neoblast plasticity regulation that are crucial for regeneration. These results will delineate the role of nucleic acids’ modification in stem cell plasticity in general, including mammalian physiology and pathology.
Objective
Planarians are freshwater flatworms that can regenerate any part of their body including an entire head. A single transplanted planarian pluripotent stem cell can rescue a lethally irradiated animal. Hence, the extreme plasticity of planarian stem cells (neoblasts) is critical for regeneration. Despite intensive research, we still do not understand how cellular mechanisms that regulate neoblast homeostasis are integrated to facilitate regeneration. In a preliminary study, I discovered that chemical modifications of nucleic acids are critical for normal neoblast function, and that animals lacking this activity fail to regenerate. This extreme neoblast phenotype suggests that these highly conserved base modifications are crucial regulators of stem cell homeostasis. In this project, I will dissect the functions of nucleic acid base modifications in vivo using high-throughput gene function screening, single cell RNA sequencing, and molecular biology methods. I will establish a mechanistic foundation for understanding the regulation of stem cell plasticity and regeneration. In particular, we will (1) analyze the functions of genes encoding nucleic acid modifiers and use planarians as a platform for discovery of unknown players, (2) elucidate the regulatory roles of the base modification machinery on stem cell function, (3) investigate the dynamics of nucleic acid base modification landscape in planarian stem cell physiology and injury. My approach will generate a systems level understanding of nucleic acid modification-based regulation on stem cell homeostasis, an emerging theme in stem cell research. The impact of these findings are far reaching and would become the basis for a deeper understanding of fundamental stem cell biology, including mammalian physiology and pathology.
Fields of science
- natural sciencesbiological sciencesbiochemistrybiomoleculesnucleic acids
- natural sciencesbiological sciencescell biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- medical and health sciencesbasic medicinepathology
- medical and health sciencesbasic medicinephysiologyhomeostasis
Programme(s)
Topic(s)
Funding Scheme
ERC-STG - Starting GrantHost institution
69978 Tel Aviv
Israel