Statement of Work_Babagana_Thermal_Stress_OCT2023_Finalized_Redacted.pdf

Statement of Work (SOW)

Project: Reducing Operational and Training-Related Heat and Cold Stress Injuries:

Identifying Novel Pharmaceutical Targets

GENERAL INFORMATION

1.0 Scope of Work:

The Naval Medical Research Unit Dayton (NAMRU-D) is conducting a funded study that includes research support from a team with a background in animal thermal stress, bioinformatics, and pathway delineation. This study requires a combination of unique equipment including a single cell sequencer, automated animal brain processer, and animal husbandry facilities. Funding has been provided to NAMRU-D from the Defense Health Agency under the FY23 Interservice

Restoral Program.

The project discussed is titled: Reducing Operational and Training-Related Heat and Cold Stress Injuries: Identifying Novel Pharmaceutical Targets– Period of performance beginning with receipt of funds (received on JUN2023) and ending 30

SEP 2024.

The objectives are to identify cell-type specific physiological responses to thermal stress which will allow for a deeper understanding of the novel pathways engaged during mild and intense thermal stress. The desired outcome is a knowledge product describing results of the study, which may take the form of conference abstract(s) and/or peer-reviewed publication(s).

2.0 Background:

Heat stress is a long-recognized problem in the military and a growing public health concern. Heat-related injuries (e.g., heat syncope, heatstroke) can result from prolonged exposure to high temperatures or excessive physical exertion. Heatstroke is considered life-threatening with a mortality rate ranging from ~21-63%.

Furthermore, ~3-28% of heatstroke survivors suffer from neurological and peripheral tissue damage or other complications. These poor survival and morbidity rates underscore our limited understanding of the underlying pathophysiology of heat stress and our inability to effectively treat it. Meanwhile, cold injuries are not only mission ending, but they also result in high rates of disability. Despite adequate training, procedures and equipment, cold-injuries continue to occur in a variety of training and operational environments.

Heat stress induces a physiological response, commonly referred to as the heat shock response (HSR), that involves the upregulation of multiple heat shock proteins to maintain protein homeostasis. Moreover, cold stress induces the activation of several pathways that affect thermogenesis and metabolic processes.

However, it is not clear what cell types or regions of the brain upregulate (or downregulate) these processes as not every cell responds the same to a particular thermal stress.

Elucidating the cell-type specific physiological response to thermal stress will allow for a deeper understanding of the novel pathways engaged during mild and intense heat stress, in addition to those involved in cold stress. Identifying these pathways will provide the impetus for future pharmaceutical and diagnostic research; and thus, lead to advances in monitoring, prevention, diagnosis, and the treatment of thermal injuries. Ultimately, pharmaceutical and diagnostic aids to combat thermal injuries will help warfighters overcome planning and executional challenges associated with training and operations where thermal stress is a concern.

Briefly, our experiments will consist of heating and cooling animals to recapitulate mild or extreme heat/cold stress. Whole brains will be subsequently extracted and processed into single cell populations. Cells will undergo single cell RNA sequencing to discern gene expression patterns at the cellular level.

REQUIREMENTS

3.0 Technical Requirements/Tasks:

To successfully execute the project, the support team would need to fulfill the following requirements within the period of performance described above:

• REQUIREMENT:

o Must have readily available expertise and equipment for animal surgery and biotelemetry o Must have readily available expertise in transcriptomics, including scRNA analysis, and signaling pathway analysis.

o Must have peer-reviewed journal publications in the fields of cell stress and thermal biology, demonstrating expertise in these areas.

Tasks performed across the project stated above:

• Acquire and house all 40 training and experimental mice (C57BL6 -

Male/Female, 8 weeks of age)

• Write and submit all necessary animal approvals requests and protocols (e.g., Institutional Animal Care & Use Committee Protocol)

• Perform unique animal biotelemetry surgeries and animal health assessments as necessary

• Provide laboratory experimental space, animal heating and cooling equipment, the necessary access privileges and technical assistance, as needed, for

NAMRU-D staff to execute work at contractor lab.

• Provide the gentleMACS™ Dissociator with Heaters for experimental use

• Transport (e.g., shipping via FedEx) all 16 samples on dry ice to the scRNA processing facility

• Work with the NAMRU-D staff and support teams to interpret the scRNA data

• Report findings together with NAMRU-D team in conference abstract(s) or peer-reviewed publication(s) (e.g., co-author manuscript) and remain available to address potential reviewer comments

4.0 Government Furnished:

NAMRU-D will be responsible for the following tasks:

• Furnishing all consumable supplies for animal brain isolation, not including the purchase and housing of experimental or training mice

• Perform all animal brain extractions on euthanized animals, with assistance from the support team, as needed

• Liaison with Sequencing Core identified by the government to secure professional expertise, equipment, and analysis of scRNA work

• Work with support team to interpret data figures

• Assist writing reports for government publication and manuscripts to journals and/or conference proceedings

• Share senior authorship with support team Co-PI for any peer-reviewed publications

• Submit publication and cover associated fees

5.0 Deliverables / Schedule:

Key Deliverables

Item

No.

Deliverable

Objective

Due

1 Proposed Project

Plan

Defining the responsibilities, timeline, risks, and milestones of contract objectives.

No later than thirty (30) business days after contract award

2 Periodic Status

Meetings

Discuss status, barriers to progress, and research planning

As needed.

Meetings may be held virtually.

Updates and discussions may occur over e-mail

3 Final Report Document contributions, including any unique design and/or data analysis contributions; significant findings; lessons learned

No later than thirty (30) business days after end of period of performance

6.0 Travel: Data collection will occur at the Roswell Park Comprehensive Cancer

Center (RPCCC). The support team is responsible for any of their staff (or team) related travel costs. The NAMRU-D is responsible for any government related travel costs. Regular communication via e-mail, phone, or video will ensure successful execution of the project. The leader of the support team is expected to attend a conference where the results of the study will be presented.

7.0 Support Team Key Personnel:

Key personnel must have research experience and expertise in the area of thermal stress, animal manipulations and surgeries (e.g., IP surgery, Biotelemetry device implantation), bioinformatics, RNA expression data analysis, IACUC protocol submission and manuscript preparation, evidenced by a history of publications involving the subject matter.

Positions key to successful performance of the contract include: professor/research faculty, postdoctoral fellow(s), graduate research associates/assistants, and research technicians.

8.0 Data Rights:

Each Collaborator shall have title to all Data generated by that Collaborator. Each

Collaborator agrees to provide all Data to the other Collaborator and hereby grants

Unlimited Rights in Data that does not contain Proprietary Information.

For Data that contains the Non-Navy Collaborators’ Proprietary Information, the

Government has rights to: 1) Use, modify, reproduce, release, display, or disclose

Technical Data within the Government without restriction; and 2) Release or disclose Data outside the Government and authorize persons to whom release or disclosure has been made to use, modify, reproduce, release, display, or disclose that Data for any U.S. Government purpose (purposes where the U.S. Government is a Collaborator) including competitive procurement.

For Data that contains NAMRU-D’s Proprietary Information, Non-Navy

Collaborators have rights to use, modify, reproduce, release, display, or disclose

Technical Data within the Non-Navy Collaborators’ organization, in whole or in part, and in any manner, for any internal purpose excluding commercial purposes. If

Non-Navy Collaborators are subsequently awarded a Government contract that entails deliverables that incorporate NAMRU-D’s Proprietary Information, such deliverables must be delivered with at least Government Purpose Rights, as defined in the DFARS § 252.227-7013.

The Non-Navy Collaborators shall have a Limited Right to use, reproduce, or disclose Data that may describe one or more Inventions in which the Government owns or may own a right, title, or interest, if such Data are provided by NAMRU-D under this Agreement. This Limited Right does not grant the Non-Navy

Collaborators any License to any Invention in which the Government owns or may own a right, title, or interest. In accordance with Article 7.5 below, such Data are to be held in confidence.

The Collaborators shall have Unlimited Rights in any Data that are not Proprietary

Information or protected under 35 U.S. Code § 205 provided under this Agreement.

NAMRU-D have a Limited Right to use, reproduce, and disclose only to

Government employees for use in support of the Cooperative Work any Data that are properly marked as Proprietary Information and are provided by the Non-Navy

Collaborators under this Agreement. Such Proprietary Information can be used only for the purpose of performing the Cooperative Work unless written consent to other use or disclosure is obtained from the Non-Navy Collaborators.

The Non-Navy Collaborators shall have a Limited Right to use, reproduce, or disclose Data that may describe one or more Inventions in which the Government owns or may own a right, title, or interest, if such Data are provided by NAMRU-D under this Agreement. Such Data shall be properly marked by NAMRU-D.

Except for the rights granted in Article 7.1 and Article 7.2, Data shall be protected in accordance with the proper markings of its owner and as provided by, at a minimum, the requirements of 15 U.S. Code § 3710a. Proprietary Information will be protected only if it is properly marked as such. Information provided in intangible form that is Proprietary Information must be designated Proprietary

Information at the time it is provided, followed within fifteen (15) days by a writing summarizing the exact information to be protected. The Collaborator receiving

Information in an intangible form that is designated as Proprietary Information shall be responsible for protecting the Information as Proprietary Information during the fifteen (15) day notification. After the fifteen (15) day period, if no written summary has been received, the receiving Collaborator need not continue to protect the Information received in intangible form.

Data that is provided by the Non-Navy collaborator in the performance of this

Agreement, and is appropriately marked as a trade secret or commercial or financial information that is privileged or confidential under 5 U.S. Code § 552(b)(4), shall not be disclosed by NAMRU-D. The Parties shall agree to not disclose, for up to five (5) years, Data that is produced by the NAMRU-D and that would have been considered a trade secret or commercial or financial information that is privileged or confidential if it had been produced by the Non-Navy collaborator.

CI, CUI, or otherwise restricted information shall be protected in accordance with the security laws of the U.S.