NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

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

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government - including the NIH Intramural Program.
• U.S. Territory or Possession

Non-domestic (non-U.S.) Entities (Foreign Institutions) 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.

Applicant organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) 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. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• 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.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but 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 DUNS number and 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.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH 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 SF424 (R&R) Application Guide.

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 his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support. SenNet especially encourages applications from individuals who are not already funded either as Contact PD/PI or as MPI in previously issued SenNet RFAs.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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 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 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 or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. 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 Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. 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.

Letter of Intent

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Viviana Perez
National Institute on Aging (NIA)
Telephone: 240-328-7301
Email: [email protected]

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

Instructions for the Submission of Multi-Component Applications

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required, Minimum 1, maximum 1
• Administrative Core: Minimum 1, maximum 1
• Biological Analysis Core: Minimum 1, maximum 1
• Data Analysis Core: Minimum 1, maximum 1

Overall Component

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Research & Related Other Project Information (Overall)

Follow standard instructions.

Project/Performance Site Locations (Overall)

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Research and Related Senior/Key Person Profile (Overall)

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

Demonstrate strong scientific expertise in the areas that are critical to the success of the application. Describe any experience in successfully leading the coordination of data intensive activities, and management and analysis of high-throughput analyses such as those pursued by the SenNet.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

Budget (Overall)

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

Leadership Effort Commitment: The TMC contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person-months of effort. For applications with multiple PDs/PIs, a minimum effort of 1.8 person-months is required for the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required.

mTMC Program Manager: Based on the complex roles the mTMC will play within the SenNet, the mTMC PD(s)/PI(s) are strongly encouraged to propose and budget for a mTMC Program Manager to manage day-to-day operations and work with the other SenNet PD(s)/PI(s), NIH staff, and SenNet Investigators to manage and coordinate the mTMC activities.

Travel Funds: The budget should include sufficient funds to support travel for SenNet activities, including but not limited to supporting the travel and participation of PD(s)/PI(s) and other mTMC members at twice yearly SenNet Steering Committee meetings.

Collaborations: Starting in year 2, at least 10% of the budget should be set aside for collaborative activities, including visits to other murine or human TMCs or other collaborating entities, sharing of expertise and materials, and other collaborations as deemed necessary or beneficial by the Steering Committee, or by NIH staff.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

PHS 398 Research Plan (Overall)

Specific Aims: Specific Aims should address the three subsections described below (Overall TMC Research Strategy, Management Strategy; Goals and Milestones; and Resource Sharing Plan).

Research Strategy: Provide an overview of the structure of the mTMC. Describe the vision and goals of the mTMC and how these contribute to accomplishing the overall goals of SenNet. Succinctly describe the tissue maps that will be generated. State how the maps constructed within the mTMC will expand knowledge of the relationship between cellular senescence and health, development, or responses to challenges. Briefly describe the relevance of the research products and resources to be generated by the mTMC activities for SenNet and the wider research community. Provide goals and milestones for the entire mTMC. The applicant must provide a detailed description of the mTMC's vision and organization. In lieu of the standard sub-sections listed in the SF424 (R&R) Application Guide, the Research Strategy must consist of the following modified sub-sections:

Tissue Mapping Center Research Strategy: Provide a description and rationale for the major theme and structure of the mTMC, its goals and objectives, and background information to provide feasibility of accomplishing these goals. Explain the rationale for tissue/organ selection and prioritization, innovation and synergy between the tissues and organs chosen, and the assays deployed. Describe the timeline for the mTMC, highlighting when each Core will start, the rationale for this timing and the ramping up of protocols. Outline how the range of tissues and technologies will be expanded during the project. Provide plans for activities to be performed during the setup and scale-up phases of SenNet, and how the mTMC will lay the groundwork for longer-term plans, including how the work may be expanded to include additional types of data and/or a wider range of organs and mouse strains. In addition, propose a plan for coordination and collaboration within the Consortium, with other human and murine TMCs and the CODCC. Describe synergies and possible collaborations with other initiatives or the wider research community that would enhance the productivity of the mTMC.

Tissue Mapping Center Management Strategy: Without duplicating information present in the biosketches, applicants should provide evidence of successful management of large, multi-component programs and prior experience with generating significant, high quality imaging and omics data as part of a Consortium. In addition, the overall strategy should describe how the skills of individual team members will translate into the collective capability of the mTMC, how the team brings complementary multidisciplinary scientific expertise required for the integration of multidimensional, multiparametric data and how the diverse expertise of the team members increases the capability for innovation, the ability to anticipate new directions, and the flexibility to redirect research when needed.

Goals and Milestones: Applicants are required to define a clear set of annual milestones for the proposed project that are consistent with the goal of developing widely useable, high-quality tissue maps. Explain the overall strategy for achieving the goals and objectives of the mTMC and how the different components of the mTMC will interact to achieve these goals. Specifically, applicants must provide a timeline with milestones and details of how the mTMC will ramp-up data generation and analysis during the funding period. The applicant should also describe metrics associated with evaluating achievement of milestones and what action will be taken, and when, if a milestone is not met or is significantly delayed. Applicants should describe how they will prioritize their activities to ensure that the goals of SenNet will be achieved. Milestones may be revised at the time of the award and yearly as described in the terms and conditions of a Cooperative Agreement below.

Letters of Support: Provide all letters of support that are appropriate, including any letters of support from institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the mTMC and its goals. The parent institution is expected to provide documented evidence of space dedicated to the needs of the mTMC, protected time to devote to mTMC activities, staff recruitment, dedicated equipment, or other financial support for the proposed mTMC. Both the parent institution and pertinent departments should provide assurance of their commitment to the mTMC.

If collaborative linkages are being developed between the mTMC and other centers in related areas, a letter of agreement from the collaborating Center PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be directly involved in the Center's research activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

The following modifications also apply:

• All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan. The Center must establish appropriate data sharing policies and data access procedures consistent with the provision of data to the public with a minimal embargo period. Applicants need to indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the SenNet and approved by NIH staff. A primary goal of the SenNet is to lay the foundation for a widely accessible atlas of cellular senescence and this will require data and resources to be shared quickly and openly once validated. Restrictive licensing and sharing practices for SenNet-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees need to manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of SenNet data, tools, and resources for research purposes will be considered as hindering the goals of the SenNet and will be considered non-responsive. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, as members of the Steering Committee, and in collaboration with the CODCC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.
  
  Leveraging the Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) Initiative - A key component of the Common Fund Data Ecosystem is enabling computing in a cloud environment. Applicants who anticipate requiring >$10,000 direct costs in commercial cloud services from either Google or AWS in any one year of the anticipated award are expected to request in-kind support via the Common Fund STRIDES partnerships rather than requesting direct cost support for these services. To request in-kind support for cloud services via STRIDES, applicants must outline the anticipated costs of commercial cloud services in the Budget Justification section, including, but not limited to, data storage, analysis, data movement/egress, professional services, training, and related activities. Please review NOT-RM-20-009 for important details about how to provide this information in your application. NIH staff will work with award recipients and their institutions to establish STRIDES accounts as needed.

PHS Assignment Request Form (Overall)

All instructions in the SF424 (R&R) Application Guide must be followed.

Administrative Core

Budget (Administrative Core)

Core Leader: The Core Leader of this core must devote a minimum of 1.8 person months of effort to the Administrative Core of the SenNet. For applications with multiple Core Leaders, a minimum effort of 0.8 person-month is required for the Contact Core Leader and 0.6 person-month of effort per additional Core Leader is required.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Pilot projects: The mTMC may allocate a minimum of $20,000 and up to $50,000 direct costs each year to the Pilot and Feasibility Program (up to two pilots), which will be administered through the Administrative Core.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

SF424 (R&R) Cover (Administrative Core)

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

PHS 398 Cover Page Supplement (Administrative Core)

Specific Aims: State the specific aims for the Administrative Core and provide a rationale and description of how each aim enhances the operation of the Center and its value to the SenNET.

Research Strategy: In lieu of the standard Research Strategy sub-sections (Significance, Innovation, Approach), use the sub-sections defined below to explain how the Administrative Core will effectively administer and coordinate the Center's activities:

Leadership Plan: Describe the leadership team and how components of the mTMC, including key personnel, will interact within the mTMC itself and with the broader SenNet and NIH program staff. Describe prior experience in working as part of a research network or other large-scale collaborative activities to meet individual and group goals, including examples of such prior work. Describe how decisions will be made by the leadership team and carried out. Describe mechanisms to ensure effective internal management of ongoing research activities across the mTMC and participation in Network activities such as teleconferences, development of SOPs etc. Describe plans for soliciting, selecting, reviewing, and administering the pilot projects. Describe how synergy and integration within the mTMC and with the other murine and human TMCs will be fostered. The parent institution should provide assurance of its commitment to continuing support of the mTMC in the event of a change in directorship and a well-defined succession plan should be in place.

Tissue Mapping Center Coordination Plan: Provide an overview of the mTMC organization including coordination and interactions between the different mTMC Cores. Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions. Describe how the Administrative Core will manage and coordinate communication, day-to-day activities, collaborations, and resource and data sharing within the mTMC. Describe plans for assessing progress of the mTMC to meet its goals and milestones. Describe and, preferably, demonstrate through presentation of preliminary data strategies for how the components of the mTMC will work together to minimize confounding variables in data generation.

Network Coordination Plan: Describe plans for collaborating with other SenNet sites and NIH program officials to design or improve Network operations and implement protocols. Describe plans to work with the CODCC to optimize strategies for data collection and analysis, and to facilitate public access to SenNet data through the CODCC including who will be accountable for data submission to the CODCC. Describe plans for collaborating with other murine and human TMCs on topics including but not limited to SOPs, assay protocols and data analysis. State willingness to adhere to Network-wide policies and procedures established by the NIH and the SenNet Steering Committee, including data access, publication, and intellectual property policies. Applicants should also describe plans for, and willingness to abide by, Memoranda of Understanding and other sharing agreements potentially needed for data and biospecimen sharing within the Network and other related programs.

Letters of Support:

Provide all letters of support that are appropriate for this core, including any letters of support from institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the mTMC and its goals. If collaborative linkages are being developed between the mTMC and other centers in related areas, a letter of agreement from the collaborating Center PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be directly involved in the Center's research activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan. Applicants need to indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the SenNet and approved by NIH staff.

A primary goal of the SenNet is to lay the foundation for a widely accessible atlas of cellular senescence and this will require data and resources to be shared quickly and openly once validated. Restrictive licensing and sharing practices for SenNet-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees need to manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of SenNet data, tools, and resources for research purposes will be considered as hindering the goals of the SenNet and will be considered non-responsive. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, as members of the Steering Committee, and in collaboration with the CODCC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Biological Analysis Core

Budget (Biological Analysis Core)

Budget forms appropriate for the specific component will be included in the application package.
Core Leaders: The Core Leader of this core must devote a minimum of 1.8 person months of effort to the Biological Assays Core of the SenNet. For applications with multiple Core Leaders, a minimum effort of 1.5 person-month is required for the Contact Core Leader and 1 person-month of effort per additional Core Leader is required.
Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Biological Analysis Core)

Specific Aims: The Biological Analysis Core is at the core of the activities of the mTMC, and it should effectively and efficiently contribute to the overall objectives of the mTMC and SenNet. State the specific aims for the Biological Analysis Core and provide a rationale and description of how each aim addresses a specific aspect of generating a map of cellular senescence of the chosen tissues or organs.

Research Strategy: Applicants should highlight aspects of their proposed activities that speak to the significance and innovation of the approach. In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Biological Analysis Core using the sub-sections listed below.

Biospecimen Management: Describe the rationale for choosing strains and tissues to be analyzed, Applicants must propose use of C57/BL6 (any sub-strain) and at least one additional strain such as Balb/C or models such as the Collaborative Cross, Diversity Outbred or HET-3. This list is not exhaustive, and an appropriate justification of the models chosen will be expected. Importantly, while murine models genetically engineered to facilitate detection of senescent cells are allowed, genetically engineered mice used to model disease are not eligible. The ultimate selection of strains and organs/tissues to be analyzed within the Biological Analysis Cores of the consortium will be prioritized by the mSenNet steering committee, and applicants should state in their application whether they have flexibility to focus on strains and/or tissues different from the ones they are proposing as primary targets. The Biological Analysis Core must specify that analysis of both sexes will be performed, and ages of animals to be analyzed should be specified. Tissues to be analyzed also need to be specified, with preference given to those tissues already approved for analysis in the human portion of SenNet (brain (cortex and hippocampus), spinal cord, heart, lung, pancreas, kidney, skeletal muscle, bone marrow, lymphoid nodes, skin, colon, fat, breast, placenta and ovary). A minimum of 5 tissues will need to be analyzed in depth (i.e., in 3D at the single cell level), while additional tissues can be analyzed at less depth (2D, but still at the single cell level) as a way of increasing tissue coverage. Provide an overview of how tissues will be collected and handled so as to preserve tissue integrity and biological properties. Indicate quality control measures that will be applied to ensure the harvested tissues are of the best possible quality, consistent with the goal of the TMC.

Characterization Pipeline: Provide a general overview of the assays that will be deployed and the various data types that will be collected to characterize cellular senescence in the selected tissues. Provide a biological justification for data type, analytical approach, and data volume to be acquired that is motivated by the maps to be constructed. Describe the reproducible, quantitative, and sensitive nature of the assays to be deployed and any strategies used to calibrate and optimize them. State if technologies proposed within the application can be considered analytically validated. If not, provide plans and timelines for analytical validation. Provide a workflow for data collection that describes how high-content, high-throughput data at high resolution will be collected for comprehensive characterization of each biospecimen. If assays are in different geographical areas, provide a plan for how biospecimens will be divided or transported for analysis. Describe a strategy to monitor and ensure the quality of instrument performance and data generated across the mTMC. Applications should describe typical error rates for the proposed assays and steps for data quality management.

Scaling and Standardizing the Pipeline: Describe plans for how the data generation pipeline will be scaled up during the project, including expectations for different datasets to be generated such as preliminary data, calibration data, validation data, and production data. Provide a plan to work collaboratively with other murine and human TMCs when/if harmonization is needed. Describe plans for scaling the pipeline including how emerging technologies may be incorporated into the pipeline, optimization of existing assays to enhance throughput or building additional analytical capacity.

Biomarkers: Describe plans for developing comprehensive, dynamic, and searchable sets of biomarkers of cellular senescence, including both cellular and secretome aspects, in the tissues under investigation. Provide strategies aimed at verifying the accuracy and reliability of the detection method and formulating a hypothesis for testing the association between the biomarker or biomarker signature and the senescent state of cells/tissues.

Models: Describe plans for developing innovative models to study cellular senescence and the SASP, including the development of ex vivo approaches such as explants, artificial organoids, 3-D cultures, or other models as applicable.

Perturbations: Describe in detail how the mTMC will employ perturbations as confirmation tools related to findings in the unperturbed animals, to gain insights into cellular senescence phenotypes and biomarkers. Perturbations of cellular senescence include different inducers, as well as interventions such as senolytics, senomorphs, immune therapies and others.

Imaging: Discuss technologies and analytical tools to permit spatio-temporal visualization, tracking and tracing of senescence cells and their environment in vivo and ex vivo, including whole body imaging if appropriate. Discuss plans for building additional analytical capacity to accommodate new or updated imaging, single cell, or other technologies developed through the Technology Development Projects component of the SenNet.

Letters of Support:
Provide all letters of support that are appropriate for this core, including any letters of support from institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the mTMC and its goals. If collaborative linkages are being developed between the mTMC and other centers in related areas, a letter of agreement from the collaborating Center PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be directly involved in the Center's research activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan. Applicants need indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the SenNet and approved by NIH staff. A primary goal of the SenNet is to lay the foundation for a widely accessible atlas of cellular senescence and this will require data and resources to be shared quickly and openly once validated. Restrictive licensing and sharing practices for SenNet-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees need manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of SenNet data, tools, and resources for research purposes will be considered as hindering the goals of the SenNet and will be considered non-responsive. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, as members of the Steering Committee, and in collaboration with the CODCC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

Data Analysis Core

Budget (Data Analysis Core)

Budget forms appropriate for the specific component will be included in the application package. Core Leaders: The Core Leader of this core must devote a minimum of 1.8 person months of effort to the Data Analysis Core of the SenNet. For applications with multiple Core Leaders, a minimum effort of 0.8 person-month is required for the Contact Core Leader and 0.6 person-month of effort per additional PD/PI is required.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Leveraging STRIDES for Cloud Computing Activities: The NIH Science and Technology Research Infrastructure for Discovery, Experimentation, and Sustainability (STRIDES) initiative has established partnerships with commercial cloud service providers (CSPs) Google and Amazon Web Services (AWS) to provide favorable pricing for cloud-based costs. The NIH Common Fund, managed by the Office of Strategic Coordination, is using the STRIDES partnerships to provide in-kind support for CSP costs. For more details, please see NOT-RM-20-009.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

PHS 398 Research Plan (Data Analysis Core)

Specific Aims: State the specific aims of the Data Analysis Core, describing how it will assemble cellular senescence maps from the selected tissues and upload data to the CODCC.

Research Strategy: Applicants should highlight aspects of the proposed activities of the Data Analysis Core that speak to the significance and innovation of their approaches. In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Data Analysis Core using the sub-sections listed below. Describe the outputs from the mTMC that will be submitted to the CODCC and the process for doing this.

Data Processing: Describe and demonstrate any existing or proposed data processing pipelines to be employed within the mTMC. State how these pipelines might be scaled to meet the demands of increased throughput within the mTMC. State the degree to which the resulting processed data is interoperable and meets the qualifications for FAIR data sharing standards. If pipelines that are standard in the field are not being employed within the mTMC, provide justification for the use of in-house pipelines and provide examples of downstream analyses utilizing the output of the pipeline (to demonstrate interoperability). Describe a plan for assessing and managing data quality including identification of missing or out of range data, calibration drift, or user variability. Describe how the core will harmonize data processing with other murine and human TMCs and within the SenNet as a whole. Collaborate with the CODCC to build QA/QC management tools that can determine missing, incomplete and erroneous data, sources of technical noise, as well as developing statistical and other approaches to annotate or correct the data to ensure that only high-quality data is released and displayed to the public. Quality measures should accompany all data generated by SenNET and available through the SenNET portal.

Data Analysis: Describe and demonstrate the computational approaches that will be employed within the Data Analysis Core that will result in the generation of multiscale, multiparameter maps from high-content imaging and omics data from the Biological Analysis Core. As appropriate, describe strategies that will be used to integrate multiscale data from different assays; integrate disparate omics and imaging data types; automate image analysis to extract and annotate features; and systems biology approaches to connect disparate data. Describe how the core will harmonize data analysis with other murine and human TMCs and within the SenNet as a whole.

Map Construction: Describe and demonstrate plans to aggregate and integrate data and metadata from the broad range of experimental and computational approaches outlined throughout the application to build high quality maps of cellular senescence in tissues under investigation in the mTMC. As appropriate, describe how samples from the same strain or multiple strains can be analyzed to understand variability, how ontologies, visualization and image analysis tools will be used to interpret that data and build different maps. Describe plans to develop or adapt computational tools for searching, cross-validation, and data visualization. Describe plans for how data analysis and map generation can optimize the data generation pipeline of the Biological Analysis Core.

Consortium Coordination: Describe plans to work with the CODCC and other TMCs to develop common data formats and interoperable tools and procedures allowing seamless integration and presentation of the maps generated by the Network. Describe how proposed analysis workflows or pipelines can be shared and harmonized across the Network. Demonstrate through evidence of collaboration and/or open-source algorithm and computational tool development the flexibility of the Data Analysis Core to incorporate disparate data types from emerging technologies incorporated after award. Analytical flexibility is an important aspect because the breadth of data types across the Consortium and technologies that may be employed in the future is currently unknown.

Letters of Support:

Provide all letters of support that are appropriate for this core, including any letters of support from institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the mTMC and its goals. If collaborative linkages are being developed between the mTMC and other centers in related areas, a letter of agreement from the collaborating Center PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be directly involved in the Center's research activities.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, must address a Data Sharing Plan. Applicants need indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the SenNet and approved by NIH staff. A primary goal of the SenNet is to lay the foundation for a widely accessible atlas of cellular senescence and this will require data and resources to be shared quickly and openly once validated. Restrictive licensing and sharing practices for SenNet-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees need manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of SenNet data, tools, and resources for research purposes will be considered as hindering the goals of the SenNet and will be considered non-responsive. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, as members of the Steering Committee, and in collaboration with the CODCC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Prior to funding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 1. 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. Overview Information 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) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential fieldof the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applications Involving the NIH Intramural Research Program

Should intramural scientists submit an application through this FOA, or should an extramural application include a collaboration with NIH intramural scientists, the requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above and as described in the NIH Intramural Source Book.

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Significance

Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA:

Are the murine models proposed commonly used and of particular value in pre-clinical research? Are the assays proposed essential to the mission of the mTMC and the SenNet? Will the data and knowledge generated by this mTMC provide sufficient metadata to create reliable high content maps of the tissues chosen? Do the Cores contribute substantially to the overall objectives of the mTMC?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA:

Do the mTMC PD(s)/PI(s) and their team demonstrate evidence of working productively in collaborative environments and in large, distributed scientific projects?

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA:

If novel approaches are proposed, are they well-justified and likely to contribute to the overall mTMC and SenNet? Do the mTMC PD(s)/PI(s) propose innovative solutions to meet and manage consortium coordination?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

Specific to this FOA:

Overall: Have issues of rigor and reproducibility been adequately addressed? Is the data sharing plan adequate to the needs of SenNet? Do the applicants have a robust plan for sharing and dissemination of data produced by the mTMC?For the Administrative Core: Are the plans for communicating and collaborating with the CODCC and NIH staff appropriate and likely to facilitate overall program objectives?

Are the plans for submitting data, protocols, and making resources available to the SenNet Consortium acceptable? Will there be coordination, communication, cohesiveness, and synergy among the components of the mTMC as they relate to achieving the overall objectives of the Network?

For the Biological Analysis Core: Is there a solid plan for interaction with the other components of the mTMC, including the Administrative and Data Analysis Cores? Do the preliminary data demonstrate the capabilities of the Biological Analysis Core to rapidly deploy the proposed molecular, cellular, and tissue-level characterization assays proposed? If the investigators propose technologies for biospecimen analysis that have not been analytically validated, will the technologies be fully validated and capable of contributing data generated by the mTMC within the proposed timeframe? Will the Biological Analysis Core likely achieve the throughput and content necessary to build maps that are FAIR (Findable, Accessible, Interoperable, Reusable) compliant?

For the Data Analysis Core: Are statistical analyses, procedures, and policies adequate, appropriate, and consistent with accepted standards? Is there a strong scientific foundation for the range of data processing, analysis, and computational modeling proposed? How well do the preliminary data demonstrate the validity of approaches that are not field standards? This includes data processing, analysis, computational modeling, visualization, and other algorithms. How well do the plans of the Data Analysis Core ensure that data and algorithms are interoperable and meet the qualifications for FAIR data-sharing standards?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA:

Does the institutional support indicate a dedicated and stable commitment for the duration of the project? Are these resources adequate to support the project? Are administrative structures in place for the day-to-day management of the mTMC, including mechanisms for internal quality control of ongoing research? Are the staffing, equipment, and other resources that are available to the mTMC sufficient and relevant to meeting the goals?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Protections for Human Subjects

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1); (1) Sharing Model Organisms; and (2) Genomic Data Sharing Plan (GDS).

Authentication of Key Biological and/or Chemical Resources:

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Budget and Period of Support

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

3. Anticipated Announcement and Award Dates

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

Section VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in theNIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Grantee institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) 2 CFR Part 200 Administrative Regulations, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, NIH's Grants Policy Statement (which implements the aforementioned HHS Regulations (45 CFR Part 75), 2 CFR Part 200 and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the recipients is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or play a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility reside with the recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below:

The PD(s)/PI(s) will have the primary responsibility for:

• Planning and conducting the operations defined by the terms and conditions of the cooperative agreement award.
• Overseeing the scientific development of the mTMC, reporting results to the scientific community, and disseminating approaches, methods, models, software, tools, and tissue maps and the atlas broadly.
• Committing and maintaining throughout the life of the SenNet mTMC a minimum of 1.8 person-months of effort per year for the investigator designated as the contact PD/PI.
• Committing and maintaining throughout the life of the SenNet mTMC a minimum of 1.2 person-months of effort per year for any investigator designated as an MPD/MPI of the mTMC.
• Serving on the SenNet Steering Committee. The SenNet mTMC PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) is required to serve as a member of the Steering Committee.
• Agreeing to be an active participant in the SenNet, including attending the semi-annual Steering Committee Meetings, participating in other network-sponsored meetings and workshops, and participating in collaborative activities.
• Abiding by the governance of the SenNet and all program policies agreed upon by the SenNet Steering Committee and approved by NIH Program Officials to the extent consistent with applicable rules and regulations.
• Maintaining the confidentiality of the information developed or handled by the SenNet mTMC, including, but not limited to: unpublished data, informatics tools, protocols, data analysis, confidential exchanges between members of the SenNet, etc. Refer to the Confidentiality Disclosure Agreement section below.
• Working closely with SenNet data generators to ensure that data, metadata, models, software, and completed atlases developed by the SenNet are deposited in the SenNet Data Portal in a timely manner that is consistent with SenNet policies.
• Leveraging technology and informatics, algorithms, tools and resources developed by other components of the SenNet consortium.
• Leveraging, where feasible, technology from related NIH-sponsored informatics initiatives, such as, for example, the Human Tumor Atlas Network, Human Biomolecular Atlas Program (HuBMAP) and Human Cell Atlas (HCA), which supports the development of informatics algorithms, tools, and resources across the continuum of tissue atlas mapping research at single-cell resolution.
• Coordinating with and leveraging, where feasible, the technology of the Common Fund Data Ecosystem (CFDE), a program that provides an infrastructure to make diverse research data broadly available and to maximize their reuse and impact.
• Facilitating the public release and dissemination of results, data, reagents, technologies, completed tissue maps and atlases, and other products generated by the SenNet mTMC in a timely manner, consistent with achieving the goals of this program. The release and dissemination will be consistent with sharing policies and recommendations developed and approved by the SenNet Steering Committee and NIH sharing policies.
• Prior to completion or termination of the SenNet mTMC project, the Recipient, in consultation with the NIH program staff, is responsible for ensuring all data, metadata, models, software, and completed tissue maps and atlases developed by the mTMC remain accessible to the research community.
• Organizing scientific working groups to facilitate collaborative projects and cross-testing of experimental and analytical concepts.
• Reporting progress to the NIH Program Officials on all SenNet mTMC activities biannually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff members as requested.
• Being prepared for in-person or virtual annual site visits of NIH Program staff members and participation in the NIH-coordinated evaluation of the SenNet program.
• Meeting annually with other murine and human Tissue Mapping Centers, as requested by NIH Program staff, to help coordinate the sharing of data, research resources, tools/platforms, and access to newly established biorepositories.

Recipients will retain ownership of the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies and must be prepared to deliver them to an NIH-designated recipient at the conclusion of the program. Participating SenNet Research Center members are also encouraged to organize and participate in other SenNet meetings and workshops, organize collaborative activities, and promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups.

NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• One or more designated NIH Program staff members will have substantial involvement as Project Scientist(s) for the SenNet. Additionally, an NIH Program Director (serving as the NIH Program Official) will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.
• The specific roles of the substantially involved NIH staff members include the following activities:
  • Serving as non-voting members of the SenNet Steering Committee.
  • Assisting the Steering Committee, the SenNet CODCC, and individual recipients in avoiding unwarranted duplications of effort across the SenNet.
  • Assisting the recipients as a resource in facilitating their broader interactions with other NIH programs to disseminate results, tools, and models from the mTMC and take advantage of existing NIH resources and infrastructures. This will specifically include acting as a liaison between the mTMC, the SenNet hTMCs and other atlas-building programs.
  • Ensuring that the mTMC data and tools are shared in a reasonable and expeditious way.
  • Evaluating the effectiveness and facilitating consortium-wide adoption of data- and tool-sharing and interoperability practices.
  • Reviewing the progress of the SenNet recipients (including SenNet TMCs), conducting periodic site visits, and taking other actions as needed.
  • Participating in organizing semi-annual SenNet meetings, specialized workshops, and webinars of the network.

Progress Reviews. The annual evaluation by the Program Officer will be based on the non-competing application and progress report, mTMC records, and assessments by the Project Scientist(s). The NIH staff will review the management, performance, and utilization of the project. If concerns are identified by the Program Officer, the Project Scientist(s) will work with the PD(s)/PI(s) to develop plans to address them in the next year of support. In addition, NIH staff may conduct interim reviews of scientific progress beyond the normal yearly non-competing progress review to determine progress and may use information from progress reviews to inform future funding for the project.

Special Reviews. Funds may be restricted pending completion of key award or consortium milestones independently of prior performance concerns. However, if concerns are identified about the performance or the management of the project, the Program Officer may conduct special reviews of the project as he/she deems necessary. NIH may engage outside experts to assist in these reviews. If concerns about the project arise and are not resolved, NIH may reduce or restrict the budget or reduce the term of support to phase out the project. In the event of long-term incapacitation of resource facilities, NIH may reduce the budget or term of support to phase out the project. Before any modifications are made, NIH staff will engage with the recipients in a positive manner and as allowed by the Cooperative Agreement mechanism to resolve performance issues in a timely manner where possible.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee is the main governing body for the SenNet. The Steering Committee is composed of one representative (contact PD/PI or other senior-level investigator) from each SenNet initiative (both murine and human Tissue Mapping Centers (TMCs), Technology Development Projects, and the SenNet CODCC) for the duration of the respective project who will have one vote each.

NIH program staff members will participate in SenNet Steering Committee meetings as non-voting members, but Steering Committee decisions will be subject to final review and approval by the NIH.

If needed, other government staff members may also participate in SenNet Steering Committee meetings as non-voting members.

Chairpersons for the Steering Committee will be selected at the first meeting of the Steering Committee following award issuance and will serve on a rotating basis as and when needed. All SenNet Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The SenNet Steering Committee meets monthly by videoconference and in-person at the SenNet semi-annual Steering Committee Meeting, or as needed.

The SenNet Steering Committee:

• Identifies scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH Program Officials for addressing such issues.
• Reviews progress of the SenNet toward meeting the overall Network goals.
• Ensures that all SenNet members utilize the resources developed by the SenNet CODCC, TMCs and Technology Development Projects.
• Coordinates dissemination of Network output to the broader senescence research community.
• Ensures that the Network takes advantage of existing NIH resources and programs.
• Establishes, as necessary, subcommittees to ensure progress of the individual Centers and the Network.

In order for recipients to fully comply with NIH and consortium data sharing policies as detailed above, all recipients will be expected to agree to a Confidentiality Disclosure Agreement (CDA) containing the following Statement of Confidentiality: The parties fully understand the potential confidential nature of discussions and presentations and acknowledge that materials provided, and discussions held prior to and during meetings may reveal confidential information. The Parties agree to respect and maintain the confidentiality of any non-public information that is received or become aware of through participation in workshops, meetings, and teleconferences associated with the NIH Common Fund sponsored grants in this program: Cellular Senescence Network Program. Public information is classified as (a) is within the public domain prior to the time of the disclosure by the Disclosing Party/Parties to the Receiving Party/Parties or thereafter becomes within the public domain other than as a result of disclosure by the Receiving Party/Parties or any of its representatives in violation of this Agreement; (b) was, on or before the date of disclosure in the possession of the Receiving Party/Parties; (c) is acquired by the Receiving Party/Parties from a third party not under an obligation of confidentially; or (d) is hereafter independently developed by the Receiving Party/Parties, without reference to the information received from the Disclosing Party/Parties. The Parties will maintain this confidentiality for a period of 7 years from the disclosure date or until the Confidential Information is classified as public information based on a-d listed herein, whichever is earlier. The parties will not use such information for their personal benefit or for the benefit of their family or associates of organizations to which they are connected or with which they have a financial involvement. Any breach of this agreement may be referred to the HHS Office of General Counsel. As to the party’s participation in the development and conduct of these programs, the party’s opinions and decisions will be based on their scientific judgment and medical or specialty expertise and will not knowingly be related to any other interest in organizations that may provide equipment, products or services to the studies.

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM)about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Viviana Perez, Ph.D.
National Institute on Aging (NIA)
Telephone: 240-328-7301
Email: [email protected]

Center for Scientific Review (CSR)
Email: FOA_[email protected]

Jessi Perez
National Institute on Aging (NIA)
Telephone: 301-402-7739
Email: [email protected]

Section VIII. Other Information

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 and 2 CFR Part 200.