Deciphering the Molecular Puzzle: IMP1 Modulation of Mucus Integrity in Necrotizing Enterocolitis

Summary

This research proposal aims to define the role of the mRNA-binding protein IMP1 in intestinal mucus composition and survival during Necrotizing Enterocolitis (NEC) in premature infants.

What they want

The project will investigate how Imp1 expression impacts intestinal mucus composition throughout NEC pathogenesis and define the requirement for Qsox1 in Imp1-mediated survival in NEC. The approach involves using Imp1 genetic mouse models combined with an experimental NEC-like intestinal injury model to analyze mucus glycosylation, permeability, ultrastructure, and intestinal proteomics. Key findings will be confirmed in human NEC tissue. The research will also define Imp1 target mRNAs and the Imp1 binding site within Qsox1 via crosslinking RNA immunoprecipitation, and crossbreed Imp1 overexpressing and Qsox1 knockout mice to determine Qsox1's role in Imp1-mediated NEC survival.

Deliverables

Establish Imp1 as a regulator of mucus in NEC
Generate novel data connecting Imp1 to Qsox1 regulation and intestinal mucus
Use proteomics to uncover mechanisms by which Imp1 promotes survival in NEC
Define new pathways that could be leveraged for NEC prevention or treatment

Technical requirements

Imp1 genetic mouse models
Experimental NEC-like intestinal injury model
Crosslinking RNA immunoprecipitation