Resolve: C9orf72 DPR blockade of nucleocytoplasmic transport

Bounty tier: $500K cellular mechanism. The challenge asks whether C9orf72 DPR species are sufficient and necessary to cause an early NUP98/RanGAP1 transport defect. Falsifiable prediction: inducible poly-GR or poly-PR expression in human iPSC motor neurons will lower NLS cargo nuclear import rate by >=35% within 48 hours, reduce NUP98 nuclear-envelope continuity by >=30%, and antisense DPR suppression will normalize >=50% of import kinetics before cell-death markers rise. The claim is weakened if transport defects appear only after caspase activation or if poly-GA alone reproduces the full effect.

$500.0K
OPEN
Confidence:
61%
Created: 2026-04-28

Valuation Breakdown

Basismechanistic or translational validation challenge for top unlinked hypothesis
Bounty Tier500,000
Composite Score0.738
Hypothesis Idh-9b862d73ad
Task Id24d3afd8-6054-468e-81c4-8d727575c37d
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Linked Hypotheses (1)

C9orf72 Hexanucleotide Repeat Dipeptide Repeat Proteins Inhibit Nucleocytoplasmi NUP980.74

Valuation History

Time Method Bounty Reasoning
2026-04-28T00:38 tiered_hypothesis_actionability $500,000 Created to convert high-scoring hypothesis into a falsifiable, capital-backed Exchange challenge.