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Transposon control as a checkpoint during regeneration

US · IL NIH grant awarded #nih-5F32EY034778-03

Summary

This research project aims to investigate the novel hypothesis that the control of transposable elements (TEs) is a necessary checkpoint for complex tissue regeneration, using zebrafish as a model organism.

What they want

The project will test the hypothesis that TE activation is a hallmark of tissue injury that must be suppressed for successful regeneration, and an inability to suppress TEs will stall regeneration. It will specifically examine the role of the Piwi pathway in suppressing TE activity during zebrafish eye regeneration. The approach involves a 2-pronged strategy combining multimodal genomics and manipulative experimentation. First, TE upregulation will be established as a hallmark of tissue injury by profiling TE expression changes across five regenerating tissues using publicly available single-cell transcriptomic data. Second, a multi-omic single-cell dataset will be generated to assess TE expression changes during cone regeneration from injury to functional recovery. Lastly, the project will directly test whether TE repression is required for regeneration by modulating TE activity using Piwi pathway mutants and chemical inhibitors.
Deliverables
  • First direct assessment of the role of TE activity and regulation during complex tissue regeneration
  • Foundation for new testable hypotheses surrounding differences between regeneratively competent versus incompetent organisms
  • Development of novel regenerative therapies
Technical requirements
  • Zebrafish retinal regeneration model
  • Multimodal genomics
  • Manipulative experimentation
  • Bulk RNA-seq data analysis
  • Single-cell transcriptomic data analysis
  • Multi-omic single-cell dataset generation
  • Piwi pathway mutants
  • Chemical inhibitors of TE activity
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