Request for Proposals

Background

The HNRNP-RNDDs have yet to be modeled using patient-derived cells, specifically iPSC-derived neural progenitor cells (NPCs), neurons, and organoids. This funding opportunity focuses on SYNCRIP-RNDD to answer key questions about disease mechanisms.

Fibroblast cell lines from multiple patients with SYNCRIP-RNDD are available and continue to be collected. Three iPSC lines derived from SYNCRIP-RNDD patients are available. RNAseq data from these cell lines will be available for analysis by late 2026.

Key Questions to Address

• What is the level of RNA and protein expression in iPSC-derived neuronal cells?
• Is there mislocalization of SYNCRIP, and does this vary by variant type?
• Are other hnRNPs dysregulated and/or dysfunctional?
• What neuronal processes are disrupted by damaging SYNCRIP variants?
• Are iPSC-derived cells a good model to test therapeutics?
• What are appropriate biomarkers for assessing potential therapeutics?

Required Components

Proposals MUST include:

• Patient-derived iPSC neuronal cell studies as the major thrust
• At least one aim involving neuronal characterization (MEA, electrophysiology, or similar)
• At least one aim involving RNAseq, eCLIP, mass spectrometry, or similar high-throughput studies

Timeline

Letter of Intent (3 pages max)

• Brief, high-level description of proposed project and specific aims
• CV of Principal Investigator

Full Proposal Requirements

• Cover Letter (1 page)
• Project Site Locations and resources (1 page)
• Senior/Key Personnel with CVs
• Budget for $300,000 over two years (1 page) — Note: Indirect costs not covered
• Research Plan (up to 8 pages)