The Defense Advanced Research Projects Agency (DARPA), through its Biological Technologies Office (BTO), has released the official solicitation for High-throughput Unmasking of Biological Interactomes with Binding Landscape Emulators (HUBBLE). The program seeks computational capabilities to map human protein-protein interactions and identify new diagnostic and therapeutic targets for traumatic brain injury (TBI). Required abstracts are due November 5, 2026, at 3:00 PM ET.
Following the Proposers Day announcement we covered in September, the new Program Announcement establishes the technical requirements and submission process for HUBBLE’s initial 12-month Phase 1. DARPA anticipates multiple awards through Other Transactions (OTs) for Research with fixed payable milestones.
What is DARPA HUBBLE Seeking?
HUBBLE aims to build a context-aware “hypercatalog” of more than 10 million new protein-protein interactions across the human proteome. The capability must capture how interactions change across cell types, time points, environmental conditions, and other biological perturbations. TBI will serve as the program’s initial test case.
DARPA is seeking approaches that combine computational modeling, simulation, and experimental benchmarking to:
Reduce the dimensionality of protein interaction energy landscapes.
Scale interaction predictions across the human proteome.
Model protein pairs, larger complexes, and multivalent condensates, including both soluble and transmembrane proteins.
Characterize binding properties beyond a binary prediction, including binding energy, residence time, and contact residues.
Validate predictions against accessible experimental datasets and government-provided benchmarks.
Phase 1 targets an initial interactome of approximately 100,000 interactions across more than 10 conditions. The anticipated 18-month Phase 2 would expand to 10 million unique interactions across more than 50 cellular contexts. This solicitation awards Phase 1 only, but submissions must describe a strategy for both phases. Phase 2 participants will be selected from Phase 1 performers.
Who Should Consider Applying?
DARPA encourages submissions from large and small businesses, nontraditional defense contractors, universities, and research institutions capable of meeting the program’s requirements. Relevant capabilities include computational structural biology, molecular simulation, machine learning, high-performance computing, and protein interaction validation. Neurotrauma-related experience is encouraged but not required.
Approaches focused exclusively on de novo designed binders without capturing endogenous human proteins are out of scope. The solicitation also excludes exclusively experimental hypercatalog-generation approaches involving more than 60% of the budget and approaches unable to meet required throughput or resource needs. Human subjects research should not be proposed.
Key Dates and Submission Requirements
All proposers must submit an abstract through DARPA’s Broad Agency Announcement Tool (BAAT), using Attachment A’s template and page limits. DARPA will evaluate technical comprehension, team capability, and the realism and affordability of the proposed cost rough order of magnitude. Selected proposers will be invited to submit an Oral Proposal Package and deliver an oral presentation. Attendance at Proposers Day was not required to apply.
Applicants should also review the solicitation’s Government Purpose Rights expectations, fixed payable milestone structure, and CMMC Level 1 self-assessment requirements when preparing their pursuit.
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