HEAL Initiative: Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome (R03) is sponsored by National Institutes of Health (NIH). Supports pilot projects to identify new targets for pain treatments as part of the initiative to address the opioid crisis and improve pain management.

PAR-25-154: HEAL Initiative-Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome (R03 Clinical Trial Not Allowed) This funding opportunity was updated to align with agency priorities. Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) Components of Participating Organizations National Center for Advancing Translational Sciences ( NCATS ) National Institute on Alcohol Abuse and Alcoholism ( NIAAA ) National Institute of Arthritis and Musculoskeletal and Skin Diseases ( NIAMS ) Eunice Kennedy Shriver National Institute of Child Health and Human Development ( NICHD ) National Institute of Dental and Craniofacial Research ( NIDCR ) National Institute on Drug Abuse ( NIDA ) National Institute of Neurological Disorders and National Center for Complementary and Integrative Health ( NCCIH ) Funding Opportunity Title HEAL Initiative-Early-Stage Discovery of New Pain Targets Within the Understudied Druggable Proteome (R03 Clinical Trial Not Allowed) March 31, 2025 - This funding opportunity was updated to align with agency priorities.

Carefully reread the full funding opportunity and make any needed adjustments to your application prior to submission. April 4, 2024 - Overview of Grant Application and Review Changes for Due Dates on or after January 25, 2025. See Notice NOT-OD-24-084 .

August 31, 2022 - Implementation Changes for Genomic Data Sharing Plans Included with Applications Due on or after January 25, 2023. See Notice NOT-OD-22-198 . August 5, 2022 - Implementation Details for the NIH Data Management and Sharing Policy.

See Notice NOT-OD-22-189 . Funding Opportunity Number (FON) Companion Funding Opportunity See Section III. 3.

Additional Information on Eligibility . Assistance Listing Number(s) 93. 350, 93.

273, 93. 866, 93. 846, 93.

853, 93. 213, 93. 279, 93.

865, 93. 121 Funding Opportunity Purpose The purpose of this notice of funding opportunity (NOFO) is to solicit applications for pilot projects to identify new druggable targets for pain within the understudied druggable proteome. Awards will support generation of preliminary data and/or tools around eligible understudied protein(s) listed in this NOFO.

This NOFO is intended to jumpstart research on understudied proteins within the context of pain and pain management and provide applicants with sufficient funding to perform basic biochemical and/or biological work to further the characterization of understudied proteins to identify new druggable targets for pain.

This NOFO is part of the Helping to End Addiction Long-term ® Initiative, or NIH HEAL Initiative ® , to accelerate the development of novel medications to treat all aspects of the opioid addiction cycle, including progression to chronic use, withdrawal symptoms, craving, relapse, and overdose Open Date (Earliest Submission Date) The following table includes NIH standard due dates marked with an asterisk.

Renewal / Resubmission / Revision (as allowed) AIDS - New/Renewal/Resubmission/Revision, as allowed All applications are due by 5:00 PM local time of applicant organization. Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

Required Application Instructions It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide , except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts ). Conformance to all requirements (both in the Application Guide and the NOFO) is required and strictly enforced.

Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

There are several options available to submit your application through Grants. gov to NIH and Department of Health and Human Services partners. You must use one of these submission options to access the application forms for this opportunity.

Use the NIH ASSIST system to prepare, submit and track your application online. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants. gov and eRA Commons to track your application.

Check with your institutional officials regarding availability. Workspace to prepare and submit your application and eRA Commons to track your application. Part 1.

Overview Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description Section II.

Award Information Section III. Eligibility Information Section IV. Application and Submission Information Section V.

Application Review Information Section VI. Award Administration Information Section VII. Agency Contacts Section VIII.

Other Information Part 2. Full Text of Announcement Section I. Notice of Funding Opportunity Description This study is part of the Helping to End Addiction Long-term ® Initiative, or NIH HEAL Initiative ® , to speed scientific solutions to the national opioid public health crisis.

The NIH HEAL Initiative bolsters research across NIH to (1) improve treatment for opioid misuse and addiction and (2) enhance pain management. More information about the HEAL Initiative is available at: https://heal. nih.

gov/ . This notice of funding opportunity (NOFO) aims to promote innovative research to increase knowledge of understudied proteins in the context of pain and pain management. The submission of small research grant (R03) applications is encouraged from institutions and organizations proposing projects leading to a better understanding of eligible proteins listed below.

Small research (R03) grants provide flexibility for initiating discrete, well-defined projects that realistically can be completed in one year and require only limited levels of funding.

This program supports different types of projects including, but not limited to, the following: Pilot or feasibility studies; Small, self-contained research projects; Development of research methodology; and/or Development of assays to support compound screening projects; Development of human cell or animal based models.

These awards will support generation of preliminary data and tools around eligible understudied protein(s) with the intent of elucidating the function of these proteins in the context of pain and obtaining sufficient preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. These grants are non-renewable.

This Funding Opportunity Announcement does not accept applications proposing clinical trial(s). The goal of this notice of funding opportunity (NOFO) is to provide a needed opportunity for the collection of preliminary data around the role of understudied proteins in the context of pain and pain management.

This NOFO would provide funding to support research that will identify new targets for pain among the understudied proteins of the Druggable Proteome (DP). Many understudied proteins have been linked to pain or pain perception, acute and chronic pain. This indicates that there could be many more proteins within the DP that could serve as markers and/or drug targets for novel pain treatment and/or pain management.

It has been recognized through workshops and publications that understudied proteins become illuminated when (1) there are tools to study the protein (e.g., tools that modulate protein activity) and/or (2) there is biochemical, cellular, or animal model evidence of disease/physiological relevance.

This NOFO was developed to address the need for expanded research and validation experiments on eligible understudied protein(s), with the intent of producing preliminary data to address the lack of biochemical, cellular, or animal model data associated with many understudied proteins.

It is expected that the award will be used to obtain preliminary data and/or research resources for subsequent grant applications and/or drug discovery projects. These projects should be carried out in a short period of time with limited resources as defined by the funding mechanism.

Understudied proteins eligible for study under this NOFO are from well-established druggable protein families with a high potential to impact human health once a disease association is made.

Proteins considered eligible for this funding opportunity have a Pubmed score of less than 10 (derived from text mining Pubmed extracts, this counts the number of publications that focus on a particular protein, and includes fractional counting of abstracts that mention multiple proteins [ Pletscher-Frankild’s et al. 2015 ]) and have minimal funded awards associated with their study.

Proteins open for study under this NOFO: SHANK3, CLCA3P, FXYD6P3, CALHM4, KCNMB2, CACNG6, CALHM5, LRRC38, KCNK7, CACNG7, CACNG5, KCTD3, CALHM3, OTOP3, LRRC8B, CACNG3, TMEM109, LRRC55, CACNG8, TMC3, PKD1L2, OTOP2, TMEM63B, TMC7, TMEM63A, ENKUR, LRRC8E, LRRC52, PKD2L2, CLDN17, TM9SF2, FXYD4, CALHM2, LRRC8D, KCNK12, TMC5, TTYH2, CACNG4, CACNG1, KCNAB3, LRRC8C, TTYH3, KCNMB3, KBTBD13 DANCR, SRY, TRBC1, TRBC2, TRAC, HSFX4, HSFY1, HSFX3, SUPT20HL2, SUPT20HL1, TRBD1, TGIF2LY, TRAV38-1, TRAV30, TRAV34, TRAV40, TRBV4-1, TRBV4-2, TRAV8-1, TRBV5-5, TRBV5-8, TRAV9-1, TRAV9-2, TRAV26-1, TRAV26-2, TRBV13, TRBV18, TRBV19, TRBV24-1, TRBV29-1, TRAV4, TRBV6-5, TRBV7-4, TRBV16, TRBV10-1, TRBV10-2, TRBV11-3, TRBV12-3, TRBV12-4, TRBV12-5, TRAV17, TRAV18, TRAV19, TRAV22, TRAV23DV6, TRAV24, TRAV29DV5, TRAV2, TRAV35, TRAV36DV7, TRAV39, TRAV3, TRAV41, TRAV5, TRAV8-2, TRAV8-4, TRAV8-6, TRBV6-2, TRBV6-4, TRAV12-3, TRBV6-8, TRAV13-2, TRBV7-6, TRBV7-7, TRBV27, TRBV28, TRBV10-3, TRBV11-1, TRBV11-2, TRBV20-1, TRAV38-2DV8, TRAV10, TRAV1-1, TRAV1-2, TRAV14DV4, TRAV16, TRAV20, TRAV21, TRAV25, TRAV27, TRBV2, TRBV30, TRBV3-1, TRAV6, TRAV7, TRBV4-3, TRBV5-1, TRBV5-4, TRAV8-3, TRBV5-6, TRBV6-1, TRBV6-3, TRAV12-1, TRAV12-2, TRBV6-6, TRAV13-1, TRBV6-9, TRBV7-2, TRBV14, TRBV7-8, TRBV7-9, TRBV9, TRBV25-1, ZFY, ZNF806, TRBJ1-1, TRAJ3, , NFE4, TAF9, RHOXF2B, ZBTB49, ZNF287, DMRTC1, ZNF19, GTF3C6, RFX8, TCF24, GTF2H2C, ZNF280C, ZNF317, ZNF157, TAF4B, ZNF595, TAF6L, C16orf89, ZNF280D, ZNF253, OVOL3, BTF3L4, AKNAD1, GTF3C3, CSRNP2, GABPB2, KCTD21, ZNF449, DMRTC2, KCTD6, GTF3C5, HES2, PHTF2, GPBP1L1, DMRTB1, FHL5, NKX1-1, IKZF5, GTF2E1, GPR153, HMGXB3, ZNF75D, ATF7IP2, ZNF385A, ZNF260, ELK3, NKX1-2, ARGFX, POU5F2, SP5, TAF5L, NKX2-4, TAF1D, EID3, FIZ1, FOXD4L1, GTF3C4, MYPOP, ZFP69, ZNF704, CC2D1B, GTF2A1L, ZNF195, ZNF280B, FOXB2, ZNF280A, ZGLP1, ZNF674, ZCCHC13, TFAP2D, ASCL4, DPRX, VSTM2A, ZNF81, GTF2IRD2, METTL23, GTF3C2, ZNF496, ZSCAN31, YPEL5, EDRF1, CHP2, ZFP2, GPBP1, GTF2E2, GTF2IRD2B, BHLHB9, CALCOCO1, RNF141, ZNF608, CARF, ZNF622, SPOCD1, ZNF215, ZNF304, IKZF4, TSHZ2, TFDP2, MED9, TAF1A, FOXR1, ZNF382, RHOXF2, HOXC12, NOL7, ELK1, TAF1C, PRR14, NKX6-3, GID8, RHOXF1, KIF12, TSSK4, ZNF124, ZFP37, FOXD4 SLC22A20P, SLC7A5P1, SLC7A5P2, C2orf83, SLC35E4, SLC35F4, PRELID3A, SLC22A31, SLC35E3, SLC35F6, SLC35E2A, TBC1D13, TMCO3, SVOPL, SLCO1B7, SLC35A5, SLC35E1, SLC35F5, SLC6A16, SLC35E2B, GRAMD1C, SLC25A30, MFSD5, SLC25A47, DENND4C, SLC35A4, SFXN5, SPNS3, C2CD5, SLC35F1, SLC39A3, SLC18B1, SLC35F3, RSC1A1, NIPAL1, SLC22A15, SFXN2, SLC38A10, MFSD2B, SLC22A14, ABCF3, SLC17A4, XKRX, SLC35C2, DENND3, SLC35B1, SLC41A2, SLC38A6, LIN7B, TM9SF2, SLC25A33, SLC45A1, SFXN4, SLC25A2, SLCO5A1, SLC5A10, SLC38A11, MMGT1, SLC46A3, SLC48A1, GRAMD1B, SLC38A7, ABCA10, SLC25A39, SLC43A3, SLC6A18, GRAMD1A, SFXN3, SLC25A42, RCN3, PQLC2, SLC26A11, CNNM1 CST9LP1, ERVK-7, ERVK-8, GGT3P, ERVK-8, ERVK-10, PRSS43, PRSS44, PRSS47, PRSS51, PRSS29P, ERVK-7, NPEPPSL1, PRSS41, ERVK-8, USP17L21, USP9Y, ERVK-7, FOLH1B, ERVK-8, ERVK-10, SERPINA13P, SEC11B, ERVK-9, LMLN2, MST1L, CASP12, HLA-DRB4, ERVK-8, ERVK-19, USP17L6P, ERVK-7, ERVK-24, ERVK-18, HERVK_113, ERVK-6, ERVK-21, ERVK-9, ERVK-10, ERVK-25, HERV-K104, OVOS2, OVOS1, ERVK-7, USP17L10, USP17L17, USP17L18, USP17L11, USP17L19, USP17L15, USP17L12, USP17L3, USP17L13, USP17L22, USP17L20, USP17L5, WFDC9, USP17L1, PRSS48, ITIH6, PRSS46P, SPINK14, WFDC6, USP31, PGPEP1L, ERVK-10, SPINT3, WFDC3, TMPRSS7, PRSS45, WFDC10B, SERPINA11, WFDC10A, SERPINE3, WFDC11, TMPRSS11F, COL28A1, TRIML1, TMPRSS11B, MINDY4, CPO, PRSS42, SPINK8, CAPNS2, MINDY2, NPEPL1, SPINT4, ATXN3L, WFDC8, PRSS33, CELA2B, WFDC13, PRSS36, ADAM20, RHBDL3, PSMA8, OTUD6A, ADAM30, KAZALD1, OVCH1, CARD17, CST9L, OVCH2, CAPN12, JOSD2, F2RL2, PRSS53, SPINK9, DESI1, CAPN13, PRSS22, AMZ1, SEC11C, TRABD2A, TYSND1, TMPRSS12, UFSP1, USP27X, PRSS37, MAIP1, SPCS2, PRSS54, MINDY1, METAP1D, USP17L24, SERPINB12, FBXL17, DPEP2, CSTL1, WFDC12, WFIKKN2, PSMB3, CELA2A, TMPRSS5, PRADC1, USP51, CAPN11, MMP27, PRSS35, JOSD1, CPXM1, IMMP1L, ADAM21, ZUP1, SPPL2C, CTRB2, RHBDD2, ADAM11, TMPRSS9, AMZ2, TPSD1, UFSP2, USPL1, C1RL, PRSS38, SPINK13, SPCS3, USP34, DPEP3, ADAMTS19 OR10D4P, OR10J6P, OR13C6P, OR14L1P, OR1F2P, OR2B8P, OR2I1P, OR2W5, OR2W6P, OR3A4P, OR4A4P, OR52L2P, OR52P1P, OR56B2P, OR5AK3P, OR7A2P, OR8G2P, OR8G3P, OR9A1P, VN1R17P, OR10D3, OR2B3, GPR62, CNIH4, MRGPRX3, ADGRG5, GPR156, GPR150, GPR33, PKD1L2, GPR160, EFR3A, GPR27 ONLY APPLICATIONS THAT FOCUS ON PROTEINS LISTED ON THIS LIST, AS WELL AS MEETING THE RESPONSIVENESS CRITERIA BELOW, WILL BE CONSIDERED RESPONSIVE TO THIS NOFO.

ALL OTHER APPLICATIONS WILL BE CONSIDERED NON-RESPONSIVE AND WILL BE RETURNED TO THE APPLICANT WITHOUT REVIEW. A significant percentage of the proteins within the above protein families are considered understudied, thus there is sizable opportunity for the discovery and development of new targets for pain and pain management within the understudied druggable proteome.

Sufficient justification should be provided to indicate why particular protein(s) were chosen for study in the context of their potential role in pain. Those projects employing methods that identify multiple proteins for study from the above link are acceptable but require justification as to why those proteins were chosen for study within the context of pain, beyond the fact that they are on the eligible protein list provided.

Examples of potential research areas could include: Isolation and purification of understudied proteins and in vitro/in vivo characterization with the intent of developing future novel therapeutics; Verification or placement of understudied protein(s) in signaling cascades, including upstream signals and downstream activities in order to better understand pain targets; Identification and validation of new pain biomarkers; Pre-clinical animal studies of understudied proteins focused on therapeutic development; Characterization of cell- and tissue-specific protein expression, localization, and function of understudied protein(s) in native environments as they pertain to pain; Use of novel tools to validate preliminary disease or physiological associations with understudied proteins in animal models, biomimetic systems, or ex vivo human samples; Studies to establish preliminary structure-activity-relationships (SAR) between functions of an understudied protein and its ligands (e.g., small molecules, macrocycles, synthetic peptides) for future drug discovery projects.

The NIH HEAL Initiative will require a high level of coordination and sharing between investigators. It is expected that NIH HEAL Initiative award recipients will cooperate and coordinate their activities after awards are made by participating in Program Director/Principal Investigator (PD/PI) meetings, including an annual HEAL Investigators Meeting, as well as other activities.

Applications Not Responsive to this NOFO The following types of studies are not responsive to this NOFO. Applications proposing such studies will be considered non-responsive and will not be reviewed or considered for funding.

Projects that meet the NIH definition of a clinical trial; Projects where the majority of the proposed work focuses on proteins outside of those featured in the above protein lists; Applications that propose clinical drug development studies for understudied protein(s); Applications proposing studies of diseases/conditions not related to pain and/or pain management.

National Center for Complementary and Integrative Health (NCCIH) NCCIH supports research exploring novel therapeutic targets for complementary and integrative health intervention to treat pain, opioid use disorder (OUD), and/or overdose (OD). Complementary interventions include natural products (e.g., dietary supplements, botanicals, probiotics, and microbial-based therapies).

Natural products are defined by NCCIH to include therapeutically relevant lead compounds derived from plants fungi, bacteria, marine organisms, or animals.

Additionally, psychological (e.g., meditation, hypnosis, music-based interventions, relaxation therapies), physical (e.g., acupuncture, massage, chiropractic manipulation, devices) approaches, or a combination of psychological and physical approaches (e.g., yoga, tai chi, dance therapies, some forms of art therapies), are also research topics within scope.

NCCIH is particularly interested in identification and validation of understudied proteins within druggable proteome that can be modulated with complementary and integrative health approaches in the context of pain, OUD and/or OD.

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) The mission of the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) is to support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases. NIAMS encourages investigators to discuss their research interests with NIAMS program staff prior to submitting their grant application.

In the context of this NOFO, NIAMS is interested in the investigation of understudied, novel targets that could lead to more effective and safer treatment of pain in rheumatological, orthopedic, dermatological, bone and cartilage, and muscle diseases.

National Institute of Dental and Craniofacial Research (NIDCR) NIDCR strongly encourages investigators to discuss their research interests with NIDCR program staff prior to submitting their grant application.

NIDCR encourages applications that investigate understudied, novel targets associated with orofacial pain conditions such as temporomandibular disorders, trigeminal neuropathic pain, orofacial dyskinesias and dystonias, and burning mouth syndrome. National Institute on Aging (NIA) NIA strongly encourages investigators to discuss their research interests with NIA program staff prior to submitting their grant application.

NIA encourages applications that investigate understudied, novel targets associated with pain in the context of aging and dementias to facilitate the development of safe and efficacious medications to treat and/or prevent pain in older adults and comorbidities including Alzheimer’s disease and related dementias.

NIA intends to administer applications under this NOFO that meet requirements central to NIA’s mission of improving the health and well-being of older adults through research. National Institute of Neurological Disorders and Stroke (NINDS) NINDS is interested in the discovery and development of non-addictive therapeutics to treat pain disorders.

These disorders include, but are not limited to headache, migraine, post-stroke pain, neuropathic pain, pain following traumatic brain injury, pain associated with spinal cord injury, pain associated with Alzheimer’s Disease-related dementias, pain associated with Parkinson’s Disease and chronic overlapping pain conditions. See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information Grant: A financial assistance mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity. Application Types Allowed Resubmission - Resubmission to PAR-24-197 and this NOFO.

The OER Glossary and the How to Apply Application Guide provide details on these application types. Only those application types listed here are allowed for this NOFO. Not Allowed: Only accepting applications that do not propose clinical trials.

Need help determining whether you are doing a clinical trial? Funds Available and Anticipated Number of Awards The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. Application budgets are limited to $100,000 in direct costs (excluding subcontract F&A) for one year and need to reflect the actual needs of the proposed project.

The maximum project period for an application submitted under this NOFO is 1 year. NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO. Section III.

Eligibility Information Higher Education Institutions Public/State Controlled Institutions of Higher Education Private Institutions of Higher Education Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education) For-Profit Organizations (Other than Small Businesses) City or Township Governments Special District Governments Indian/Native American Tribal Governments (Federally Recognized) Indian/Native American Tribal Governments (Other than Federally Recognized).

Eligible Agencies of the Federal Government U.S. Territory or Possession Independent School Districts Public Housing Authorities/Indian Housing Authorities Native American Tribal Organizations (other than Federally recognized tribal governments) Faith-based or Community-based Organizations Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply. Foreign components, as defined in the NIH Grants Policy Statement , are allowed. Applicant organizations must complete and maintain the following registrations as described in the How to Apply- Application Guide to be eligible to apply for or receive an award.

All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference the NIH Grants Policy Statement Section 2.

3. 9. 2 Electronically Submitted Applications for additional information.

System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually . The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.

NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM. Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM. gov registration process.

The same UEI must be used for all registrations, as well as on the grant application. eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants. gov registrations; all registrations must be in place by time of submission.

eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application. Grants. gov – Applicants must have an active SAM registration in order to complete the Grants.

gov registration. Program Directors/Principal Investigators (PD(s)/PI(s)) All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.

If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Eligible Individuals (Program Director/Principal Investigator) Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with their organization to develop an application for support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the How to Apply-Application Guide. This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement Section 1. 2 Definition of Terms .

3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct. The NIH will not accept duplicate or highly overlapping applications under review at the same time, per NIH Grants Policy Statement Section 2.

3. 7. 4 Submission of Resubmission Application .

This means that the NIH will not accept: A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application. A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.

An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2. 3. 9.

4 Similar, Essentially Identical, or Identical Applications ). Section IV. Application and Submission Information 1.

Requesting an Application Package The application forms package specific to this opportunity must be accessed through ASSIST, Grants. gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.

gov Workspace are available in Part 1 of this NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution. 2.

Content and Form of Application Submission It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced.

Applications that are out of compliance with these instructions may be delayed or not accepted for review. All page limitations described in the How to Apply- Application Guide and the Table of Page Limits must be followed. Instructions for Application Submission The following section supplements the instructions found in the How to Apply- Application Guide and should be used for preparing an application to this NOFO.

All instructions in the How to Apply - Application Guide must be followed. SF424(R&R) Project/Performance Site Locations All instructions in the How to Apply- Application Guide must be followed. SF424(R&R) Other Project Information All instructions in the How to Apply- Application Guide must be followed.

SF424(R&R) Senior/Key Person Profile All instructions in the How to Apply- Application Guide must be followed. All instructions in the How to Apply- Application Guide must be followed. HEAL Investigators’ Meeting: For budgeting purposes, include travel costs to support the attendance of one PD/PI (one person) at a 2-day, in-person HEAL Investigators meeting in the Washington DC area, annually for the duration of the award.

All instructions in the How to Apply-Application Guide must be followed. PHS 398 Cover Page Supplement All instructions in the How to Apply- Application Guide must be followed.

All instructions in the How to Apply- Application Guide must be followed, with the following additional instructions: The goal of this notice of funding opportunity (NOFO) is to jumpstart research on understudied proteins that are associated with pain and/or pain management, and to provide applicants with funding to perform basic biochemical and/or biological work to further the characterization of understudied proteins in the context of pain and pain management.

The proposed project must focus on one or more of the eligible proteins listed above. Preliminary data are not required, and appropriate justification for the proposed approach can be provided through literature citations, data from other sources, or from investigator-generated data if any are available.

The project should address critical barriers to understanding the role of understudied proteins in fundamental physiology, in disease processes, and/or as novel therapeutic agents. Applicants should provide the protein acronym(s) as listed above in Section I that will be the focus of their application at the top of page one of their Research Plan, which will allow NIH to quickly identify those projects that are responsive to this NOFO.

Proteins not listed above as eligible for study under this NOFO may only be used in projects proposed for this NOFO as controls for experiments involving eligible proteins from the approved list and shall not be the focus of experimental work. Resource Sharing Plan : Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply- Application Guide.

All instructions in the How to Apply-Application Guide must be followed, with the following additional instructions: All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan.

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan. The HEAL Initiative has additional requirements that must be addressed in the Data Management and Sharing plan. All HEAL-generated data must be shared through the HEAL Initiative Data Ecosystem following HEAL’s compliance guidance ( https://heal.

nih. gov/data/complying-heal-data-sharing-policy ). Specifically, HEAL applicants must include: Plans to submit data and metadata (and code, if applicable) to a HEAL-Compliant data repository ( https://www.

healdatafair. org/resources/guidance/selection ) and follow requirements of the selected repository. Plans to register your study with the HEAL platform within one year of award ( https://heal.

github. io/platform-documentation/study-registration/ ). Plans to submit HEAL-defined study-level metadata within one year of award ( https://github.

com/HEAL/heal-metadata-schemas/blob/main/for-investigators-how-to/study-level-metadata-fields/study-metadata-schema-for-humans. pdf ) and https://heal. github.

io/platform-documentation/slmd_submission/ ). Plans to submit variable-level metadata to the HEAL Platform at the time of sharing data or by the end of the project period, whichever comes first ( https://heal. github.

io/platform-documentation/vlmd_submission/ ) and (https://github. com/HEAL/heal-metadata-schemas/tree/main/variable-level-metadata-schema/schemas). To the extent possible, all other (non-pain) HEAL studies conducting clinical trials or research involving human subjects are expected to use questionnaires by the HEAL Clinical Data Elements (CDE) Program ( https://heal.

nih. gov/data/common-data-elements ) if applicable and relevant to their research. Studies using CDEs, regardless of whether they are part of the HEAL repository, will be required to report which questionnaires are being used.

To the extent possible, HEAL awardees are expected to integrate broad data sharing consent language into their informed consent forms. HEAL has developed additional details and resources to fulfill these requirements ( https://www. healdatafair.

org/resources/road-map ). HEAL Public Access and Data Sharing Policy: NIH intends to maximize the impact of HEAL Initiative-supported projects through broad and rapid data sharing and immediate access to publications ( https://heal. nih.

gov/about/public-access-data ). Guidelines for complying with the HEAL Public Access and Data Sharing Policy can be found at https://heal. nih.

gov/data/complying-heal-data-sharing-policy . Resources and tools to assist with data related activities can be found at https://www. healdatafair.

org/. For more detail and specific data sharing requirements, see Section 4. Other plans.

Publications resulting from NIH HEAL Initiative funded studies must be immediately publicly available upon publication. For manuscripts published in journals that are not immediately open access, authors should arrange with journals in advance to pay for immediate open access. Costs to ensure manuscripts are immediately publicly available upon publication should be included in budget requests.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply- Application Guide. No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply- Application Guide, with the following additional instructions: If you answered “Yes” to the question “Are Human Subjects Involved?

” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record. Study Record: PHS Human Subjects and Clinical Trials Information All instructions in the How to Apply- Application Guide must be followed.

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the How to Apply- Application Guide must be followed. PHS Assignment Request Form All instructions in the How to Apply- Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM) See Part 2. Section III.

1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants. gov 4. Submission Dates and Times Part I.

contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants. gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons , NIH’s electronic system for