Version history

{
  "description": "This challenge targets the hypothesis: **Repeat-domain exposure defines seed-competent tau conformers**\n\n**Hypothesis Summary:** Tau assemblies become seed-competent when their repeat-domain surfaces adopt a conformation that both survives transfer and templates monomeric tau into pathological aggregates. This conformer-specific templating mechanism, supported by structural studies of disease-specific tau filaments, suggests that the exposed repeat domain interface is the critical determinant distinguishing pathogenic from non-pathogenic tau conformations. Non-pathogenic transferred tau lacks this exposed templating inter\n\n**Falsifiable Predictions:**\n1. Pharmacological modulation of MAPT will alter neurodegeneration markers in validated models by ≥20%\n2. Genetic knockdown of the key target will reproduce the pathological phenotype in ≥2 independent model systems\n3. Patient-derived biosamples will show the predicted molecular signature (sensitivity ≥70%, specificity ≥70%)\n4. Mechanistic intervention at the proposed node will rescue neuronal viability in vitro by ≥30%\n\n**Bounty Tier:** $126,000 USD (composite score 0.760)\n**Challenge Type:** Open — any team may submit experimental evidence supporting or refuting this hypothesis\n\n**Success Criteria:** Peer-reviewed evidence demonstrating mechanistic validation of ≥2 of the 4 predictions, with independent replication.",
  "mission_id": "neurodegeneration",
  "challenge_type": "open",
  "scope": "hypothesis",
  "initial_bounty_usd": 126000,
  "current_bounty_usd": 126000,
  "bounty_confidence": 0.7,
  "gap_importance_score": 0.76,
  "urgency_score": 0.6,
  "market_price": 0.5,
  "composite_score": 0.684,
  "debate_count": 0,
  "status": "open",
  "domain": "neurodegeneration"
}