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MicroRNA directed pathway discovery in allergy and asthma

US · IL National Institutes of Health (NIH) grant awarded #nih-5R01HL109102-15

Summary

This research project investigates RNA circuits, including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and mRNA cis-regulatory sequences, that regulate Treg function and the pathobiology of allergy and asthma.

What they want

The project is organized into two scientific aims. Aim 1 will functionally characterize the empirically determined target network of miR-15/16 in Tregs and investigate the role of miR-15/16 interaction with MALAT1, testing its importance in allergic lung inflammation using novel transgenic mice with CRISPR-mediated mutations. Aim 2 will probe the biological functions of noncoding mRNA sequences implicated in asthma susceptibility and RNA regulation, using GCLiPP-directed CRISPR dissection and a deep analysis of cis-regulatory elements in the STAT6 3’ UTR with conventional reporter assays and CRISPR-directed base editing technology.
Deliverables
  • Illumination of novel RNA regulatory circuits active in allergy and asthma immunopathogenesis
  • Mechanistic insights into molecular functions of RNA regulatory circuits
Technical requirements
  • CRISPR-mediated mutation
  • GCLiPP (biochemical technique to map RNA:protein interactions)
  • CRISPR dissection
  • Conventional reporter assays
  • CRISPR-directed base editing technology
  • Novel transgenic mice
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