Resolve: TBK1-autophagy receptor failure traps G3BP1 stress granules

Bounty tier: $500K ALS autophagy validation. The challenge distinguishes defective receptor recruitment from generic stress-granule overproduction. Falsifiable prediction: TBK1 loss-of-function or kinase inhibition in iPSC motor neurons will reduce phospho-SQSTM1/OPTN recruitment to G3BP1 granules by >=50%, extend granule half-life after arsenite washout from <60 minutes to >180 minutes, and phosphomimetic OPTN/SQSTM1 rescue will normalize >=40% of G3BP1 clearance. If autophagic flux enhancement clears granules without receptor recruitment rescue, the receptor-trapping model is falsified.

$500.0K

OPEN

Confidence:

60%

Created: 2026-04-28

Linked Targets (1)

G3BP1 Ras GTPase-activating protein-binding protein 1 PDB:4FCJ0.64

🧬 View 3D Structure — PDB 4FCJ click to expand

Detected Targets:

G3BP1

3D Protein Structure

▶ View 3D structure: G3BP1 — PDB 4FCJ

Experimental structure from RCSB PDB | Powered by Mol* | Rotate: click+drag | Zoom: scroll

Valuation Breakdown

Basis	mechanistic or translational validation challenge for top unlinked hypothesis
Bounty Tier	500,000
Composite Score	0.737
Hypothesis Id	h-0c2927c851
Task Id	24d3afd8-6054-468e-81c4-8d727575c37d

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Linked Hypotheses (1)

H2: Impaired Autophagy Receptor Recruitment Traps G3BP1 Granules TBK1, SQSTM1/p62, OPTN, NDP520.74

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.