Technologies for Host Resilience (THoR) | Apply Online

Frequently Asked Questions (FAQs): Technologies for Host Resilience (THoR) - DARPA BAA 15-21

What is the THoR program?

Technologies for Host Resilience (THoR) is a DARPA Biological Technologies Office research program focused on understanding why some hosts remain relatively healthy even when infected. The program aims to uncover the core biology behind tolerant or resilient responses so those insights can be turned into practical interventions that could eventually be used in humans to lessen the harmful effects of infectious diseases.

What does THoR mean by "host tolerance" or "host resilience"?

In this opportunity, host tolerance (also described as host resilience) refers to biological strategies that limit damage and preserve function during infection. The emphasis is on reducing sickness and death even when an infectious agent is still present, rather than focusing only on killing pathogens or boosting classic immune responses.

What is the main goal of the opportunity?

The overarching goal is to discover and explain the fundamental biological relationships that enable tolerance to infection, and to develop a mechanistic understanding strong enough to support actionable countermeasures and justify later transition toward clinical use.

Is THoR about proving that tolerance exists, or explaining how it works?

THoR is explicitly centered on building a detailed mechanistic understanding of tolerance. The program is not just about observing that tolerant phenotypes exist; it is about rigorously measuring them, connecting them to underlying pathways and system-level responses, and generating evidence that can support the development of interventions.

What kinds of approaches is DARPA looking for?

DARPA is looking for novel methods and technologies that can reveal tolerance mechanisms. This includes approaches that can identify resilient phenotypes, measure them rigorously, and link them to underlying biology such as pathways and system-level responses.

How is THoR structured?

THoR is organized into three Technical Areas that form a pipeline from discovery to application: (1) identifying and characterizing tolerant phenotypes, (2) uncovering mechanisms that drive tolerance, and (3) identifying interventions that leverage those mechanisms to reduce morbidity and mortality.

What is Technical Area 1 (TA1) about?

Technical Area 1 focuses on identifying and characterizing animal hosts that show tolerant phenotypes. This includes finding individuals or populations that experience infection but show reduced morbidity, preserved physiological function, or improved survival compared to typical hosts, and documenting those phenotypes with meaningful clinical, molecular, and functional measurements.

What is Technical Area 2 (TA2) about?

Technical Area 2 focuses on moving from phenotype to mechanism by uncovering the biological processes that drive tolerance. Examples mentioned include molecular pathways, immune-metabolic regulation, tissue repair processes, inflammation control, and other host-centered responses that reduce damage without necessarily reducing pathogen burden.

What is Technical Area 3 (TA3) about?

Technical Area 3 aims to identify interventions that leverage tolerance mechanisms to reduce morbidity and mortality. The emphasis is on interventions that work through host resilience rather than direct pathogen elimination, with a clear focus on strategies that could be adapted for human use.

Does THoR require animal work?

The opportunity emphasizes tolerance as it appears in animal populations and expects integration of evidence from prospective animal studies. Prospective animal studies are described as a way to enable controlled testing and detailed sampling that can connect cause and effect.

Are retrospective datasets also part of the expected approach?

Yes. A notable feature of the BAA is the expectation that performers integrate evidence from prospective animal studies with analysis of retrospective datasets, including retrospective preclinical and human clinical datasets. These datasets can be mined to see whether tolerance-linked signals or patterns appear in real-world conditions and across different settings.

Why combine prospective studies with retrospective data?

Prospective animal studies support controlled experimentation and detailed sampling to link cause and effect, while retrospective datasets can help validate whether the same tolerance-linked patterns show up beyond a single model system. The program frames this as a way to strengthen the case that identified mechanisms are broadly relevant.

Is the program focused on pathogen elimination?

No. While infectious agents remain part of the context, THoR is centered on host tolerance and resilience: limiting damage, preserving function, and maintaining homeostasis during infection. Interventions in the program are framed as complementary options, particularly when pathogen-targeted measures are slow to develop, less effective, or challenged by resistance.

What outcomes does THoR aim to improve?

THoR is aimed at reducing morbidity and mortality during infection by preserving physiological function and reducing host damage, potentially keeping infected individuals functional and alive even when the infectious agent is present.

What is the anticipated translational direction of the work?

The program is structured to support development of actionable countermeasures and to justify later transition toward clinical use, with an emphasis in Technical Area 3 on strategies that could be adapted for human use.

What disciplines are relevant to THoR proposals?

The opportunity describes THoR as a call for interdisciplinary work at the intersection of infectious disease, systems biology, physiology, data science, and translational biomedical research.

What is the funding opportunity identifier and sponsoring organization?

This opportunity was released by DARPA as BAA 15-21 through the Biological Technologies Office.

What is the CFDA number and program category?

The opportunity is listed under CFDA 12.910 (Research and Technology Development) and is categorized as a discretionary opportunity.

What funding instrument is used?

The BAA uses an "Other Procurement Contract" instrument, reflecting DARPA's approach to funding high-risk, high-reward research and development.

Is cost sharing or matching required?

No cost-sharing or matching requirement is stated in the provided information.

Who is eligible to apply?

Eligibility is listed as unrestricted, meaning it is broadly open to a wide range of applicant types, subject to any additional eligibility details that may be included in the full announcement.

What were the key dates for this BAA?

The posted date was March 31, 2015. The original closing date was May 19, 2015. The revised closing date was June 9, 2015 at 4:00 pm Eastern. The archive date was September 30, 2015.

Who is the point of contact for the opportunity?

The point of contact listed is COL Matthew Hepburn, M.D., Program Manager within DARPA's Biological Technologies Office. The notice includes a note to reach out if there are issues accessing the full announcement electronically.

What should applicants do if they cannot access the full announcement?

The opportunity notes that the point of contact (COL Matthew Hepburn, M.D.) should be contacted if there are problems accessing the full announcement electronically.

What makes THoR different from traditional infectious disease countermeasure programs?

Rather than concentrating only on killing pathogens or stimulating classic immune responses, THoR focuses on uncovering and leveraging host-centered tolerance mechanisms that limit damage and preserve function during infection. The aim is to build the biological basis for countermeasures that reduce harm even when the pathogen remains present.