DARPA-SN-21-05.pdf

DARPA-SN-21-05

Special Notice DARPA-SN-21-05 Special Program Announcement for Defense Advanced Research Projects Agency (DARPA) /

Biological Technologies Office (BTO) Research Opportunity: Keystone

I. INTRODUCTION

This announcement describes a research thrust, entitled “Keystone,” that will focus on the early events associated with brain injury. This solicitation is released under the current DARPA BTO Office Wide Broad Agency Announcement (BAA), HR001120S0044, entitled “Biological Technologies,” which can be found at https://beta.sam.gov/opp/4efd37762ed0475d871af927279f010d/view. This special notice is soliciting proposal abstracts and full proposals to HR001120S0044. It is highly encouraged that proposers submit proposal abstracts (2 pages), which will be reviewed to determine whether or not a full proposal submission is encouraged. The requirements for the abstract and full proposal submission, evaluation, and award of any resulting awards will ultimately be subject to the terms described in HR001120S0044.

The purpose of this announcement is (1) to draw the attention of the scientific community to the Keystone study topics, (2) to initiate dialogue and teaming that will lead to team-based abstract/proposal submissions to address the Keystone study topics, (3) to share the planned timetable for the submission of abstracts and government feedback concerning said abstracts, and (4) to share the planned timetable for the submission of full proposals.

• Proposal Abstract Due Date: January 14, 2021, 4:00 PM ET

• Full Proposal Due Date: February 25, 2021, 4:00 PM ET

II. TOPIC DESCRIPTION

This special notice is designed to solicit proposals to identify the first “biological responder(s)” within milliseconds to seconds after the brain sustains a militarily relevant brain injury. The resulting studies will evaluate the first biological responder(s) (i.e., molecular or cellular responses) following traumatic brain injury (TBI) from blasts as well as unconventionally acquired brain injury (UBI) from ultrasound and electromagnetic sources.

Overview - Keystone:

Keystone seeks to leverage recent advances in neuroscience related to in vivo (preferable) and in vitro high spatial and temporal resolution molecular and imaging measurements. Although advanced measurement platforms can now obtain millisecond temporal resolution and subcellular spatial resolution, they have yet to be specifically leveraged for investigating the first biological responder(s) in the millisecond to second timescale after TBI and UBI. A few examples exist of in vivo brain injury models integrated with high-resolution measurement techniques, but none currently investigate the millisecond to second molecular or cellular responses immediately post-injury. The primary objective is to identify the first “biological responder(s),” which we define as biological factors involved in the response to brain injury within milliseconds to seconds after the brain sustains a militarily relevant brain injury. If proposers choose to address multiple injury models in their proposals, a secondary objective is to determine if the identified first biological responder(s) is the same or different depending on the energy source causing the brain injury.

These objectives can be addressed initially in in vitro systems (cells, organoids, micro-physiological systems), but ultimately must be achieved in an in vivo model of brain injury.

https://beta.sam.gov/opp/4efd37762ed0475d871af927279f010d/view

Objective:

DARPA is interested in receiving and reviewing Keystone proposal abstracts and proposals to address the current research gap related to the immediate, post-injury pathophysiology of brain injury. Accordingly, innovative submissions must identify the proposed approach to identifying key first biological responder(s) within milliseconds to seconds after a brain injury occurs from militarily relevant energy sources (blast, ultrasound, electromagnetic). Following the procedures outlined in HR001120S0044, DARPA will provide feedback to proposers on abstract submissions and indicate whether, after preliminary review, there is interest in the proposed research and submission of a full proposal on the “Keystone” research topic is encouraged or discouraged.

The key performance parameters for Keystone include successful integration of real-time measurement techniques with militarily relevant brain injury models (blast, ultrasound, electromagnetic) in vitro and in vivo. Successful integration will be demonstrated by generating real-time cellular, molecular, physiological, or imaging data within 5 seconds post injury. Of particular interest to BTO are submissions capable of achieving these measurements closer to the time of injury. The final deliverable to be generated from Keystone includes a list of relevant biological responder(s) per brain injury type, where relevance is determined by significant dysregulation (increased or decreased) either in abundance or activation from baseline. Submissions should describe the ability to integrate real-time measurement techniques into one or more militarily relevant brain injury models (i.e. blast, ultrasound, electromagnetic). Proposals should describe viable model systems, both in vitro and in vivo, that would form the basis for identifying a relevant list of the first biological responder(s) to militarily relevant brain injuries. The finalized list of first biological responder(s) per brain injury type will be identified and developed over a 12-month period of performance.

Proposals should include measurement methodology for achieving the performance metrics within the following timeline:

• 2 months - Integrate real-time measurement techniques with military relevant brain injury models (blast, ultrasound, electromagnetic) in vitro, demonstrated by generating real-time cellular, molecular, physiological or imaging data immediately post injury (< 5 seconds).

• 3 months - Preliminary in vitro results listing the first biological responders that are significantly (p < 0.05) dysregulated (increased, or decreased) either in abundance, or activation from baseline (i.e., pre-injury), informing in vivo study focus.

• 3 months - IACUC and ACURO approval.

• 5 months - Integrate real-time measurement techniques with military relevant brain injury models (blast, ultrasound, electromagnetic) in vivo, demonstrated by generating real-time cellular, molecular, physiological or imaging data immediately post injury (< 5 seconds).

• 7 months - Identify the time point at which the first biological event(s) occur in vivo after brain injury.

• 10 months - Preliminary in vivo results listing all relevant first biological responders per brain injury type. Relevance determined by significant (p < 0.05) dysregulation (increased, or decreased) either in abundance, or activation from baseline (i.e., pre-injury) animals.

• 12 months - Finalize list of first biological responder(s) per brain injury type refined by associations with molecular pathway analytics, or other correlative data linking initiators to TBI/UBI disease progression.

• 12 months – Determine if identified first biological responder(s) are the same across each brain injury energy source, if proposers evaluate multiple injury types.

In addition to describing how approaches will meet the above timeline of performance metrics, submissions must adequately address the following:

1. A description of one or more militarily relevant brain injury model(s) chosen from blast, ultrasound, and electromagnetic sources.

2. A description of both the in vitro and in vivo brain injury model system(s).

3. A description of the real-time and molecular measurement technique(s) to be integrated without affecting or being affected by the injury model.

4. A description of approaches to refine both the list of relevant first biological responder(s) and the time point at which the first biological responder(s) occur.

5. A description of how the effort will achieve the timeline of performance metrics listed above.

6. An assessment of technical risk and a description of mitigation strategies for each of the major tasks involved in identifying the first biological responder(s) to militarily relevant brain injuries.

Please note that the deadlines for Keystone study abstract and proposal submissions are different from the general abstract and proposal deadlines that are listed in HR001120S0044.

Anticipated Structure:

The Keystone study duration is twelve (12) months. The study includes gaining IACUC and ACURO approval as well as successful demonstrations of the proposed integrated models and technologies to identify the first biological responder(s) to brain injury.

III. PROPOSAL ABSTRACT SUBMISSION

For this special notice, DARPA strongly encourages that abstracts be submitted before any proposals.

The abstract submission deadline for this special notice is January 14, 2021 by 4:00 PM ET. Proposal abstracts should be submitted in accordance with the instructions in HR001120S0044 under Section 4, “Application and Submission Information.” Information on how to submit abstracts and proposals can be found on under section 4.2.4, “Submission Information,” in HR001120S0044. Proposal abstracts may not be submitted by fax or e-mail; any so sent will be disregarded.

Teaming is permitted to allow for the most accurate and thorough identification of the first biological responder(s) through the Keystone study. One contractor must be identified as the prime.

BTO will respond to abstracts with a letter encouraging or discouraging the submission of a detailed full proposal containing technical and cost volumes. This recommendation will be based on the proposed effort’s relevance to the BTO mission and the Keystone study, a preliminary assessment of the scientific or technical merit, and interest in the technology concept. A DARPA Program Manager may contact you to further discuss the idea in your abstract. This procedure is intended to minimize unnecessary cost and effort in proposal preparation and review. The submission of an abstract, or a favorable review of an abstract, is not required prior to submitting a proposal.

For abstracts that propose efforts that are considered of particular value to DARPA but either exceed available budgets or contain certain tasks or applications that are not desired, DARPA may suggest a full proposal with reduced effort to fit within expected available budgets.

A favorable response to an abstract is not an assurance that a full proposal on the abstract’s topic will ultimately be selected for award.

Abstracts should follow the same content guideline as described in Section 4.2.1, “Proposal Abstract

Format,” in HR001120S0044. The cover sheet should be clearly marked “ABSTRACT for DARPA-SN-21- 05,” and the total length should not exceed two (2) pages, excluding cover page, official transmittal letter, quad chart, and relevant appendices as outlined below. The page limitation for abstracts includes all figures, tables, and charts. No formal transmittal letter is required. All abstracts must be written in English.

The 2-page body of the abstract should address all six of the focus areas and timeline listed in the

Objective section of this special notice.

1. Militarily relevant brain injury model(s)

2. Model systems

3. Advanced measurement modalities

4. Refinement approaches

5. Timeline

6. Risk mitigation strategies

The Cover Sheet (does not count towards page limit) should include the administrative and technical points of contact (name, address, phone, fax, email, lead organization), the Special Notice number, title of the proposed project, primary subcontractors, estimated cost, duration of the project, and the label “ABSTRACT for DARPA-SN-21-05.”

Abstracts not meeting the format described above and in HR001120S0044 will be considered non-conforming and will not be considered for review. DARPA intends to use electronic mail correspondence regarding DARPA-SN-21-05. All administrative correspondence and questions on this special notice, including requests for information on how to submit an abstract or full proposal to the BAA, should be submitted to the BAA Coordinator e-mail address: BTOBAA2020@darpa.mil.

DARPA BTO encourages the use of the Federal Contract Opportunities website, http://www.beta.sam.gov, for retrieving HR001120S0044 and any other related information that may subsequently be provided.

IV. FULL PROPOSAL SUBMISSION AND AWARDINFORMATION

The full proposal submission date for this special notice is February 25, 2021 by 4:00 PM ET.

Full proposals received after that date may not be evaluated. Full proposals should be submitted in accordance with the instructions in HR001120S0044 under Section 4, “Application and Submission Information.” Proposals may not be submitted by fax or e-mail; any so sent will be disregarded. Guidance on the proposal format is provided under section 4.2.2, “Proposal Format.”

mailto:BTOBAA2020@darpa.mil http://www.beta.sam.gov/

In accordance with HR001120S0044, proposals will be evaluated using the following criteria, listed in descending order of importance:

(1) Overall Scientific and Technical Merit;

(2) Potential Contribution and Relevance to the DARPA Mission;

(3) Cost Realism;

A detailed description of each evaluation criterion is provided in HR001120S0044.

The amount of resources made available under this special notice will depend on the quality of the proposals received and the availability of funds. Although DARPA expects the above described study to be executed, DARPA reserves the right to make changes.

V. SIGNIFICANT DATES AND TIMES

Event Due Date Time Abstract Submission Due Date January 14, 2021 4:00 PM ET Full Proposal Submission Due Date February 25, 2021 4:00 PM ET

VI. POINTS OF CONTACT

Technical Point of Contact:

Dr. Eric Van Gieson, DARPA/BTO, BTOBAA2020@darpa.mil.

All inquiries should reference “Keystone” in the subject line of the email.

VII. SUBMISSION OF QUESTIONS

Any questions regarding this announcement must be provided to the Technical Point of Contact listed above. All questions shall be submitted in writing by electronic mail. Answers to questions submitted in response to this special notice will be posted to the DARPA Opportunities Page, http://www.darpa.mil/work-with-us/opportunities, under the heading for the Biological Technologies Office.

mailto:BTOBAA2020@darpa.mil http://www.darpa.mil/work-with-us/opportunities http://www.darpa.mil/work-with-us/opportunities