RFA-RM-27-007-Full-Announcement.html

Department of Health and Human Services

Part 1. Overview Information

Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

Office of Strategic Coordination (Common Fund)

This Notice of Funding (NOFO) is developed as a Common Fund initiative (https://commonfund.nih.gov/) through the Office of the NIH Director, Office of Strategic Coordination (https://commonfund.nih.gov/). All NIH Institutes and Centers participate in Common Fund initiatives. The NOFO will be administered by the National Cancer Institute (NCI) on behalf of the NIH.

Note: Not all NIH Institutes, Centers, and Offices (ICOs) participate in Announcements. Applicants should carefully note which ICOs participate in this announcement and view their respective areas of research interest at the ICO-Specific Scientific Interests website. ICOs that do not participate in this announcement will not consider applications for funding.

Funding Opportunity Title

Cellular Senescence Network (SenNet): SenNet Technology Projects (SenTecs) (UG3/UH3 Clinical Trial Not Allowed)

Activity Code

UG3/UH3 Exploratory/Developmental Phased Award Cooperative Agreement

Announcement Type

New

Related Notices

Check for any recent Notices of NIH Policy Changes that may impact application requirements.

Funding Opportunity Number (FON)

RFA-RM-27-007

Companion Funding Opportunity

RFA-RM-27-016

, UM1

Research Project with Complex Structure Cooperative Agreement

RFA-RM-27-025

, UM1

Research Project with Complex Structure Cooperative Agreement

Number of Applications

See Part 2, Section III. 3. Additional Information on Eligibility.

Assistance Listing Number(s)

93.310

Funding Opportunity Purpose

The purpose of this Notice of Funding Opportunity (NOFO) is to solicit the development of innovative senescence technologies (SenTecs), or the adaptation of existing technologies focused on identification, characterization and understanding the biological consequences of senescent cell (SnC) heterogeneity in the context of the tissue environments and secretomes to facilitate novel strategies for modulating SnCs in vivo and for predicting the outcomes of targeting SnCs in human aging and in disease conditions. These are five-year, milestone-driven awards consisting of two phases. The first two years constitute the UG3 phase and are focused on SenTec development and demonstration of technology feasibility. The following 3-years is the SenTec application UH3 phase where SenTecs continue to be optimized, refined and validated. In the final year of the UH3 award, SenTecs will undertake a demonstration project conducted in a collaborative effort within SenNet to provide further validation of the proposed SenTec. Applicants are required to submit both UG3 and UH3 projects together when responding to this NOFO. Transition from the UG3 to UH3 phases is not automatic and will occur only after administrative review of each SenTec at the close of Year 2 of the award.

Funding Opportunity Goal(s)

The Office of Strategic Coordination (Common Fund) supports research and other projects that will accelerate fundamental biomedical discovery and translation of that knowledge into effective prevention strategies and new treatments.

Key Dates

Posted Date

October 09, 2026

Open Date (Earliest Submission Date)

October 23, 2026

November 23, 2026

Not Applicable

Not Applicable

July 2027

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.

No late applications will be accepted for this Notice of Funding Opportunity (NOFO).

Due Dates for E.O. 12372

Not Applicable

Expiration Date

November 24, 2026

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.

Table of Contents

Part 1. Overview Information Key Dates 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

The Cellular Senescence Network (SenNet) Cellular senescence is a complex biological process where cells enter a state of growth arrest without dying. This state is characterized by specific changes in the senescent cell (SnC), including an increase in cell size and the production of specific molecules by the cell that constitute the heterogeneous senescence-associated secretory phenotype (SASP) used by senescent cells to influence their microenvironment. Senescent cells are known to have both a beneficial and detrimental impact on their environment and accumulate with age where they contribute to the development and progression of many age-related diseases including cancer, diabetes, osteoarthritis and neurogenerative diseases such as Alzheimer's Disease. Here, the targeted removal of senescent cells in preclinical disease models using a class of drugs called senolytics has resulted in reduced SnCs and alleviated the burden of age-related diseases suggesting a role for these drugs in the treatment of many age-associated diseases in a variety of patients. To further explore these discoveries, the NIH Common Fund (CF) launched the Cellular Senescence Network (SenNet) in 2021 to identify, characterize and map SnCs at the single cell level in several normal human and mouse tissues.

During this initial SenNet funding period, over 1,000 datasets have been generated that reflect the vast heterogeneity of senescent cells (SnCs) across human and mouse tissues and lifespan and from which tissue-specific biomarkers for senescent cells covering 18 organs have been discovered. In addition to many published scientific articles, SenNet has produced several novel tools and technologies that facilitated the identification and characterization of these rare and heterogeneous SnCs in vivo.

Continuation of SenNet will leverage all insights and advances in cellular senescence, in addition to those generated in SenNet. To date, SenNet has documented the extensive heterogeneity of SnCs and established the concept of 'senotypes' to capture the true biological diversity of SnCs as a classification system for senescent cell identities based on a collection of biomarkers that reflect molecular, functional, and other SnC phenotypic descriptors. SenNet will currently be funded through three NOFOs, RFA-RM-27-016 (UM1), RFA-RM-27-025 (UM1), and this NOFO, RFA-RM-27-007 (UG3/UH3) which supports the development of innovative senescence-related technologies or Senescence Technology Projects (SenTecs). All applicants successfully funded in response to these threeNOFOs will become members of SenNet consortium. All projects in SenNet will be funded as Cooperative Agreements and the NIH Staff will have a substantive and significant role in shaping the scientific aspects of these projects. The governing body of SenNet will be the SenNet Steering Committee led by Steering Committee co-chairs selected by NIH Staff, and who serve as PIs on SenNet projects that constitute the SenNet Consortium.

Background and Objectives of the Cellular Senescence Network (SenNet):

Senescence is a cell state characterized by durable cell-cycle arrest in response to various stressors, often associated by a pro-inflammatory phenotype, known as senescence-associated secretory phenotype (SASP). Senescent cells (SnCs) have diverse biological roles in tumor suppression, embryonic development, tissue repair, and wound healing. However, SnCs also accumulate during normal aging and contribute to the pathology of multiple age-associated diseases including cardiovascular disease, cancer, osteoarthritis, pulmonary diseases and neurodegenerative disorders. Hence, selective elimination of SnCs holds significant promise in precision medicine.

The Cellular Senescence Network (SenNet) program was established in 2021 to comprehensively identify and characterize the differences in senescent cells across the body, in various states of human health, throughout the lifespan. During the first stage of the program, the SenNet consortium made significant progress, generating and publishing many datasets characterizing senescence signatures in human and murine tissues across lifespan. These consortium-wide, synergistic efforts have further validated and extended the landscape of senescence heterogeneity across all tissues examined. More information on the resources generated by the program can be found on the consortium website, https://sennetconsortium.org/. This funding opportunity is designed to build upon the successes of SenNet to gain further biological and mechanistic insights into role of heterogeneous senescent cells in pathophysiological conditions.

SenTec Objectives and Scope This NOFO solicits applications proposing the development and application of innovative senescence technologies, or the adaptation of existing technologies, to facilitate the overall goal of SenNet, which is to understand the biological consequences of the extensive heterogeneity of cellular senescence across human tissues and lifespan with the ultimate goal of using this information to improve targeting strategies for SnCs in vivo, the healthspan of aging individuals and those with age-related illnesses in humans. The extensive heterogeneity of SnCs documented across both murine and human tissues in earlier stage of SenNet has led to a new method of SnC classification among SenNet members where SnCs are no longer classified by single biomarkers but instead by a collection of markers of phenotypic identifiers that come together to define a SnC-specific signature or 'senotype'. Therefore, SenTecs developed in SenNet should consider the complex nature of cellular senescence in the SenTec design and execution of their SenTec. SenTecs developed in response to this NOFO must be developed for use in human systems and models: tools and technologies and are expected to contribute to the core translation goal of SenNet.

A wide variety of innovative tools/technology that consider the unique complexity of human cellular senescence in vivo and are designed to facilitate the advancement of SenNet's goals will be considered responsive to this NOFO. These tools/technologies could include, but are not limited to, proposals to develop novel and innovative tools/technologies that:

Coordination A significant feature of SenNet is the strong collaborative interactions occurring among SenNet members that have provided momentum for the discoveries made in SenNet thus far. SenTecs will therefore be strongly encouraged to work closely with the other currently supported components of SenNet, including the Discovery and Validation Centers (DVCs) and/or the Data Coordination and Integration Center (DCIC) early in the program to assure that the tools/technologies under development will be integrated and scaled appropriately for use in SenNet and beyond. SenTecs will also be expected to participate in developing consortium-wide best practices for emerging approaches to data generation and compatibility, manage quality control, cleaning and harmonization of data received, conduct cross-site comparisons and test and validate technologies on multiple tissues. SenTec projects will be required to set aside approximately 10% of their UH3 year-5 budget for a collaborative demonstration project to showcase their technology to be conducted in collaboration with another SenNet group within or outside of SenNet.

The NIH Common Fund (CF) supported programs are intended to provide resources that accelerate discovery across many different biomedical research fields. These resources include large data sets and associated digital tools needed to mine and analyze the data. To maximize their impact, data sets and tools generated by the CF programs must be usable together. Towards achieving this goal, the CF created the Common Fund Data Ecosystem (CFDE), a data management infrastructure where the interconnected ecosystem facilitates scientific advances by making CF data and digital objects usable and useful both within a program and in combination with data from other programs.

NIH intends that the SenTec tools/technologies be broadly available to provide the foundations for discoveries that the community could build upon, including methods, tools, reagents, biospecimens, datasets, analysis algorithms and software. Approved projects are expected to agree to Consortium policies to rapidly share their products within the Consortium and with the external research community through the program Portal when established. The robustness, reproducibility and rapid dissemination of experimental results are critical to the success of the SenNet. It is anticipated that in some cases, conducting additional critical experiments will be important for assessing progress. Therefore, NIH Program staff, in consultation with the PD/PI, may suggest the modifcation or addition of experiments to be conducted during the award.

Award(s) made through this NOFO will work collaboratively with all SenNet components, including the DVCs and/or the DCIC to ensure continuous improvement of the program by developing, collecting, and sharing quantitative performance metrics to be attained to demonstrate the progress of the project. In carrying out stewardship of this NOFO, the NIH or its Institutes and Centers may use these metrics to assess effectiveness and communicate the impact of the program.

Responsiveness This NOFO may solicit proposals for a range of SenTecs, but to be responsive, SenTec applications should propose the development of novel tools/technologies or propose optimizing an existing tool/technology that will help advance the goals of SenNet. Here, SenTecs with potential to advance our current understanding of the biological consequences of the extensive SnC heterogeneity revealed earlier in SenNet is a priority for the SenTec program as are those SenTecs that help advance the translational aspect of the data generated in SenNet. SenTec applications should discuss the novelty and innovation of the proposed SenTec, the rationale and purpose for its development and discuss the unmet area of senescence research it will address. Responsive applications will also inform human systems and outcomes in the human lifespan and age-related illnesses even though initial proof-of-principle experiments are initially conducted in non-human models. Importantly, applications should propose an organ or tissue to serve as the proof-of-principle organ for development of the proposed SenTec, but tools/technologies developed in response to the NOFO should ideally have applicability to more than one human tissue or organ and allow for flexibility in organ selection so as to facilitate integration of the SenTec into a final group of organ systems that will serve as the focus for SenNet. Applications focused on the development of technologies with no clear consideration of senescence biology will be deemed non-responsive as will applications solely proposing single-cell transcriptomic technologies.

UG3/UH3 Funding Mechanism This NOFO uses the UG3/UH3 cooperative agreement mechanism to support the phased development of innovative senescence technologies, or SenTecs, to advance what is currently known about cellular senescence in humans. These SenTec awards will be 5-year awards with an initial 2-year UG3 cooperative agreement award that is highly milestone driven. This UG3 phase will serve as the proof-of-principle phase where SenTecs are expected to demonstrate feasibility for the development of the proposed tool/technology. The UG3 phase will be guided by 6-month milestone covering the first two years of the award and detailed in the application. The subsequent UH3 phase will fund awards for 3 years where the focus will be on scaling, optimizing, refining and validating the SenTec in multiple human tissues. Importantly, in the final year of the UH3 award, SenTecs will be required to conduct a demonstration project in collaboration with SenNet members or others outside of the consortium, using funds set aside in the SenTec budget of approximately 10%. To fulfill the demonstration project requirement, successful applicants will be encouraged to actively participate in consortium-wide meetings and activities early in the SenNet to familiarize themselves with ongoing senescence research conducted by other members in SenNet so that by the middle of year four of the award, a proposal for a SenTec demonstration project can be formulated and finalized for administrative review and approval by NIH Staff. PIs responding to this NOFO must include detailed plans for both UG3 and UH3 phases in their application and will be asked to update the description and scope of the UH3 administrative review prior to the UG3 to UH3 transition process at the end of UG3 phase in Year 2 of the SenTec award.

As a cooperative agreement and as part of the larger SenNet consortium, all SenTec applicants are expected to describe in their application how their proposed project meets the goals of the overall consortium program, how it significantly improves upon the status quo in senescence research, how it can be integrated with other technologies, and how it is ultimately capable of being scaled for multiple human tissues in a high-throughput fashion. Applicants are also expected to discuss performance, dynamic range, sensitivity and specificity of their technologies, calibration and control processes; testing, evaluation and improvement, and interoperability and usability.

SenTec applications are expected to have ambitious goals and must provide 6-month milestones for the first two years of the UG3 phase and yearly milestones thereafter. Milestones are goals that are quantifiable for measuring SenTec success in a timely manner and are key features of the SenTec program since they will serve as guides for progress made for the development of the SenTec in real time. These milestones will also be used during the UG3 to UH3 transition process and should have quantitative criteria associated with them. Prior to funding an application, NIH Program staff will contact the applicant to discuss the proposed milestones and changes may be requested by the reviewers or NIH Program staff. A final set of milestones will be specified each year in the Notice of Award. Progress towards achievement of the annual milestones and the overall goals will be regularly evaluated by NIH Program staff and they may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period.

SenTec UG3 Phase In the SenTec UG3 phase, the NIH is interested in developing and demonstrating technologies capable of identifying and functionally characterizing individual senescent cells and their context in tissue. Expected outcomes include but are not limited to:

Milestones and Transition from UG3 to UH3 The transformative technologies being developed in the SenTecs will innately be high-risk; it is anticipated that not all SenTecs will transition from the UG3 to UH3 phase at the end of the second year of awards. Transition from the UG3 to UH3 phase will depend on the availability of funds and require SenTec PIs to apply for UH3 transition by submitting a transition application for administrative review and approval by NIH Staff. Detailed guidance for this UH3 SenTec transition exercise will be provided to successful SenTec applicants shortly after initial UG3 funding. Briefly, SenTecs applying for UH3 transition are expected to detail achievements made in the UG3 phase including a demonstration of the technology showing achievement of milestones during the UG3 phase, feasibility and proof that the technology will be applicable to human systems and the evidence of active participation of SenTec groups in the consortium.

SenTec UH3 Phase During the UH3 phase, SenTecs will continue to be optimized, scaled-up, refined, and validated. Expected outcomes include, but are not limited to the:

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have an exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Pre-Application Webinar A webinar is planned to provide prospective applicants with the opportunity to receive information and ask questions about the scientific scope of this NOFO and technical details for applying. The webinar will be open to all prospective applicants. Participation in the webinar is not a prerequisite to applying to this NOFO. Prospective applicants are also encouraged to submit their questions regarding the NOFO in advance of the webinar; further details on where to submit the questions will be provided once the webinar has been scheduled. For further details on the pre-application webinar, including the time, date, and other information, please email CS2@nih.gov.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

Funding Instrument

Cooperative Agreement: A financial assistance mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this NOFO.

Application Types Allowed

New

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.

Clinical Trial?

Not Allowed: This NOFO only accepts applications that do not propose clinical trials. Note: Applications may propose activities involving human subjects that are not deemed clinical trials.

Need help determining whether you are doing a clinical trial?

Funds Available and Anticipated Number of Awards

The NIH Common Fund (Office of Strategic Coordination) intends to commit $5.4M Total Costs in FY2027 to fund up to 9 awards. Number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

Applications must not exceed $400,000 in direct costs per year during the UG3 phase and $550,000 in direct costs per year during the UH3 phase.

Award Project Period

The scope of the proposed project should determine the project period. The maximum project period is 5 years.

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

1. Eligible Applicants

Eligible Organizations

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations

Local Governments

Federal Governments

Eligible Agencies of the Federal Government

U.S. Territory or Possession

Other

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

Regional Organizations

Foreign Organizations/International Collaborations

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 not allowed.

NIH will no longer issue awards (i.e., new, renewal, or non-competing continuation) to domestic or foreign entities that involve foreign subawards/subcontracts. All NIH-funded research involving foreign subawards/subcontracts must be submitted in response to a NOFO that is specifically designated for funded international collaborations. See NIH Grants Policy Statement 16.8 Collaborative International Research Awards.

Applications involving foreign subawards/subcontracts submitted in response to this NOFO will be deemed noncompliant and will not be considered for funding. This policy applies to all monetary international collaborations resulting in foreign subawards/subcontracts, however, it does not preclude unfunded international collaborations or foreign components, funding for foreign consultants, or procurement of unique equipment or supplies from foreign vendors.

Required Registrations

Applicant Organizations 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. Foreign organizations must obtain a NATO Commercial and Government Entity (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.

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. Obtaining an eRA Commons account can take up to 2 weeks.

All PD(s)/PI(s) must be registered with ORCID. The personal profile associated with the PD(s)/PI(s) eRA Commons account must be linked to a valid ORCID ID. For more information on linking an ORCID ID to an eRA Commons personal profile see the ORCID topic in our eRA Commons online help.

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.

2. Cost Sharing 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 Number of Applications

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 (in this NOFO, in a policy notice, or other notice from NIH Guide for Grants and Contracts). 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.

Page Limitations 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.

SF424(R&R) Cover 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

Other Attachments:

1. Applications must include an Intellectual Property (IP) Strategy. Applicants are encouraged to prepare this attachment section in consultation with their institution's technology transfer officials. The section should be labeled "Intellectual Property Strategy.pdf" and may not exceed 3 pages. Include the Attachment even if IP issues are not a consideration for the project. Indicate: IP issues are not applicable and explain why.

This section should describe a dissemination plan that involves patent protection and commercialization:

Describe the IP landscape surrounding their model system. Applicants should describe any known constraints that could impede sharing of their technology (e.g., certain restrictions under transfer or sharing agreements, applicants' previous or present IP filings and publications, similar model systems that are under patent protection and/or on the market, etc.) and how these issues could be addressed with achieving the goals of this program.

Include a letter from any entity who has ownership of the IP indicating whether they will provide the technology, if there are any limitations on the studies that can be performed with that technology, agreement about public disclosure of results (including negative results), and whether there is an agreement already in place.

If patents pertinent to the technology being developed under this application have been filed, the applicant should indicate the details of filing dates, what type of patents are filed, and application status, and associated US Patent and Trademark Office links, if applicable.

Describe future IP filing plans. For a multiple-PD/PI, multiple-institution application, applicants should describe the infrastructure of each institution for bringing the technologies to practical application and for coordinating these efforts (e.g., licensing, managing IP) among the institutions.

State how IP will be shared or otherwise managed if multiple PD/PIs and institutions are involved, consistent with achieving the goals of the SenNet Research Program.

SF424(R&R) Senior/Key Person Profile

Applications must demonstrate strong scientific expertise in the areas that are critical to the success of the application and describe any experience in successfully leading the coordination of multi-component scientific activities such as those to be generated by SenNet.

R&R Budget

R&R Subaward Budget

PHS 398 Cover Page Supplement

PHS 398 Research Plan All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims:

Applicants should consider the complexity of senescence in the development of the SenTec application, address the rationale for developing the proposed SenTec, detail the scientific questions to be answered, provide the overall goal for the entire application and show how the technology will enhance translational capabilities in senescence research.

Importantly, applicants must include separately in the application Specific Aims for the UG3 phase and for the UH3 Phase and the Specific aims for both phases should be scientifically appropriate for the distinct research phases and the amount of time allotted for each phase of the project.

Research Strategy:

Within the single Research Strategy attachment, separate the information into the sections identified below. Applications will be assigned a single impact score. Organize the Research Strategy as described below.

1. Background and Significance Define the specific knowledge gap(s) and urgent needs in cellular senescence research to be addressed by the SenTec and provide a rationale for the decision to develop the SenTec.

Outline the main characteristics and applicability of the proposed tools, technologies, analytics and methods. Projects should be justified by their strong potential to inform the biological consequences of the extensive SnC heterogeneity in multiple tissues across human health and lifespan so that mechanistic discoveries made using the SenTec could be used to inform efforts to modulate SnCs in vivo in human aging and disease. Explain whether the proposed SenTec will significantly enhance work in the DVCs and/or other research communities.

If proposing a project involving a currently available technology that was originally approved for uses outside of senescence research, provide an explanation for how adoption of the technology would substantially inform SnC heterogeneity in normal and disease tissues in vivo.

2. Innovation SenTecs development in response to this NOFO are expected to be highly innovative and novel and must consider the extensive heterogeneity associated with SnCs in human aging and disease to facilitate translating discoveries made in senescence to the clinic. Proposed SenTecs should advance current knowledge of human cellular senescence in vivo in new and creative ways and applicants should describe why the SenTec offers clear and significant advantages over similar available technologies. If the proposed SenTec is optimized or adopted from an established technology, describe how it overcomes a significant/longstanding technical challenge.

3. Preliminary data Applicants should provide preliminary data if available, to support the technology's potential to achieve analytical and clinical sensitivity and specificity comparable to current technologies used in senescence research. Do not include links to websites.

4. Approach The Approach section should be subdivided in two sections, describing activities to be completed during the UG3 Phase and the UH3 Phase. It is recognized that applications in response to this NOFO may propose SenTecs at various stages of development. Therefore, the research plan and approaches in the application should be consistent with the technology development stage and stated program goals. All applications, regardless of stage category, should address plans for assessing potential utility and feasibility in identifying and functionally characterizing senescent cells in human health, and lifespan at single cell resolution.

The UG3 section should address the following areas, if applicable:

The UH3 section should address the following areas, if applicable:

5. Integration with the SenNet DVCs, SenNet DCIC and Future Directions Statement Applicants should discuss a plan to interface with SenNet's Discovery and Validation Centers (DVCs), and the Data Coordination and Integration Center (DCIC). Describe how the proposed SenTec can be used by the DVCs, and vision for these collaborations. Applicants should discuss a plan to interface with the DVCs. Describe how the research data generated by the SenTec project will be shared with the DVCs and the Data Coordination and Integration Center (DCIC). It is recognized that applicants will NOT know in advance with whom they will be collaborating because the SenNet DVCs will not be known before awards are issued. It is anticipated that here, applicants will make reasonable assumptions about the types of collaborations that will be available in SenNet and build flexibility into their research plans. Also, applicants should prepare a future directions statement to address the potential of the proposed SenTecs for senescence research beyond the UH3 phase.

6. Milestones and Timeline A timeline (Gantt chart) including milestones is required. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., appropriate objective performance targets, quantitative for go/no-go decision points such as an appropriate level of detection and coefficient of variation, or sensitivity and specificity; and timelines for assessing progress in both the UG3 and UH3 phases, including 6-month milestones for progression through the UG3 phase to the UH3 phase. Milestones and timelines for each stage must be provided in a separate heading at the end of the Approach section for each UG3 and UH3 subsection, and should:

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.

Other Plan(s):

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.

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

Delayed Onset Study Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).