Autonomous Labs Project

In progress
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Autonomous Labs Project

Working Thesis

DisMech plus OpenScientist can become an auditable experiment-suggestion layer for disease biology: DisMech stores a computable pathograph, OpenScientist searches and ranks mechanistic gaps, and a protocol layer turns selected gaps into standardized experiments that can be reviewed by humans and executed by university automation cores or cloud labs.

This is not a claim that AI should autonomously invent therapies. The useful near-term claim is narrower: AI can maintain a disease-mechanism graph, identify weak causal edges, propose bounded experiments, and package those experiments into reproducible, machine-readable protocols.

UNC Lineberger Anchor

The UNC Lineberger "Priming the pump for new cancer treatments" story is a good case study because the named investigators cover the whole loop:

Researcher DisMech/OpenScientist role Automation relevance
Ian Davis Disease-mechanism graph for Ewing sarcoma, especially EWS-FLI1 chromatin rewiring Defines causal nodes, models, and chromatin readouts
Samantha Pattenden Chromatin assay development and screening HT-FAIRE converts chromatin accessibility into an automated plate assay
David Drewry Chemical probe and medicinal chemistry infrastructure Supplies annotated compound libraries and probe optimization logic
Pengda Liu Protein-modification and targeted-degradation biology Provides degrader-style perturbations such as TF-PROTAC concepts
Lindsey James Chemical biology of chromatin regulators and degraders Shows how degrader discovery can be tied to selectivity and phenotype assays

Ewing Sarcoma Demonstrator

The strongest disease-specific demonstration is an Ewing chromatin-accessibility loop:

  1. DisMech encodes the Ewing pathograph: EWS-FLI1 fusion, GGAA enhancer reprogramming, ETV6 counter-regulation, NuRD/CHD4 repression, core regulatory circuitry, replication stress, and STAG2 modifiers.
  2. OpenScientist identifies a concrete gap: which EWS-FLI1-dependent chromatin states are causal dependencies rather than passenger accessibility changes?
  3. The platform proposes a standardized experiment: automated HT-FAIRE, ATAC-qPCR, or low-input ATAC-seq across Ewing models, perturbing epigenetic compounds, degraders, EWS-FLI1 controls, and ETV6 controls.
  4. A protocol compiler emits a reviewed protocol compatible with laboratory automation standards or a university cloud-lab/core facility.
  5. Results return as evidence: hit compounds, chromatin-state changes, transcriptional rescue, toxicity separation, and updated pathograph edges.

The corresponding curation target in kb/disorders/Ewing_Sarcoma.yaml is gap_ewing_chromatin_reversal_screen.

Protocol And Execution Layer

Candidate execution standards and systems:

Safety And Governance

The platform should keep human review as a hard gate before execution. Required checks include PI approval, institutional biosafety review where relevant, model-system and reagent provenance, protocol versioning, dose/exposure bounds, biosecurity screening, data-management plans, and curator review before any new result updates the knowledge base.

Near-Term KB Ideas

Sources