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 Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (https://dpcpsi.nih.gov/). All NIH Institutes and Centers participate in Common Fund initiatives. The FOA will be administered by the National Institute on Aging (NIA) (https://www.nia.nih.gov) on behalf of the NIH.

Funding Opportunity Title

Cellular Senescence Network: Tissue Mapping Centers (U54 - Clinical Trial Not Allowed

 

Activity Code

U54 Specialized Center- Cooperative Agreements

Announcement Type

New

Related Notices

  • January 25, 2021 - Notice of Change to Key Dates for Cellular Senescence Network (SenNet) RFA-RM-21-008. See Notice NOT-RM-21-011.
  • January 12, 2021 - Notice of Pre-Application Webinar for Cellular Senescence Network (SenNet). See Notice NOT-RM-21-010.

Funding Opportunity Announcement (FOA) Number

RFA-RM-21-008

Companion Funding Opportunity

RFA-RM-21-009 - UG3/UH3 Exploratory/Developmental Phased Award – Cooperative Agreement
RFA-RM-21-010 - U24 Resource-Related Research Projects – Cooperative Agreements

Assistance Listing Number(s)

93.310

Funding Opportunity Purpose

The purpose of this Funding Opportunity Announcement (FOA) is to establish state-of-the-art Tissue Mapping Centers (TMCs) to work within the Cellular Senescence Network (SenNet). The goal of the SenNet consortium is to identify and functionally characterize the heterogeneity of senescent cells across multiple tissues in human health, disease, and lifespan at single-cell resolution. Through collaborative efforts, the consortium will generate a multimodal, multidimensional Atlas of senescent cells in various human tissues; develop innovative tools and technologies to identify and characterize senescent cells; and aggregate data across the Network into a searchable Atlas of Cellular Senescence, ensure the utility of the database, and promote collaboration through Network engagement with the research community. The TMCs solicited through this RFA will generate the high-resolution, high-content, multiscale biomarkers and maps of cellular senescence across the lifespan and physiological states necessary to generate the Senescence Atlas. The SenNet is focused on healthy human tissues, and work in diseased tissue or animal models is acceptable only as long as it is used to support this overall goal. TMCs will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through analyses at organ, tissue and single cell level using omics, imaging and other approaches, to data integration, analysis and interpretation.

Key Dates
Posted Date

January 8, 2021

Open Date (Earliest Submission Date)

New Date February 22, 2021

Letter of Intent Due Date(s)

New Date February 22, 2021

Application Due Date(s)

New Date March 22, 2021  

All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s). 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.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

July 2021

Advisory Council Review

August 2021

Earliest Start Date

December 2021

Expiration Date

New Date March 23, 2021 per issuance of NOT-RM-21-011. (Original Expiration Date: March 9, 2021)

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.


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

  1. Use the NIH ASSIST system to prepare, submit and track your application online.
  2. Use an institutional system-to-system (S2S) solution to prepare and submit your application to Grants.gov and eRA Commons to track your application. Check with your institutional officials regarding availability.



  3. Table of Contents

    Part 1. Overview Information
    Part 2. Full Text of the Announcement

    Section I. 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. Funding Opportunity Description

     The Cellular Senescence Network (SenNet)

    The purpose for the Cellular Senescence Network (SenNet) is to catalyze the development of a framework for mapping cellular senescence and its associated secretory phenotype at high resolution, to provide atlases of cellular senescence in multiple tissues and under diverse conditions, including early development, and across the lifespan. In addition, it is expected that the SenNet will provide comprehensive sets of biomarkers describing heterogenous senescent cell states.

    The proposed Cellular Senescence Network will be funded by the NIH Common Fund as a goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. The deliverables will provide a sound platform to develop approaches for the betterment of human health. This will be achieved by:

    • generating multimodal atlases that characterize the heterogeneity and spatial distribution of senescent cells in health and across the lifespan, at single cell resolution;
    • determining reliable biomarker panels to identify senescent cells as well as their secretory properties in vivo and/or ex vivo;
    • establishing the next generation of tools, and experimental and computational model systems amenable to perturbations, necessary to construct high resolution maps and atlases of cellular senescence;
    • establishing parameters for regulating senescence, both at the level of inducers and their removal through senolytics, immune therapy, or other means;
    • dramatically improving imaging tools to identify and validate senescence at the cellular, tissue and whole-body levels.

    There are three research initiatives that comprise the program:

    • Tissue Mapping Centers (TMC) - These Centers, announced through this RFA, will generate extensive data from high-content, high-throughput imaging, omics, and other technologies as appropriate, to build, benchmark, standardize, and validate senescent cell maps at high resolution. Tissue Mapping Centers will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through data generation, integration, analysis, and interpretation.
    • Technology Development Projects – These projects will establish proof of principle and validation of the next generation of tools, techniques and methods that can be implemented by the consortium for studying cellular senescence and their Senescence Associated Secretory Phenotype (SASP). The goal is to promote the development of novel, innovative technologies to study cellular senescence in model systems and/or human tissues. Requests will be issued in FY21 and FY22. 
    • Consortium Organization and Data Coordination Center (CODCC) - The CODCC will serve as an organizational hub for the consortium. It will collect, store, curate, and disseminate all data, metadata, analyses and visualization tools, computational models, and completed tissue maps generated by the SenNet consortium. It will develop controlled access workspaces for consortium working groups, and an outfacing portal, the Senescence Atlas, to the scientific community for access to the tools, technologies, and tissue-level maps and atlases developed by the TMC and Technology Hubs.

    Successful applicants to this funding opportunity announcement will become members of the larger SenNET, composed of investigators who have been funded in response to at least one of the three SenNET FOAs. All projects within the SenNET will be funded as Cooperative Agreements, so that NIH staff will have a significant role in shaping the scientific aspects of the project. During the first year of the award, each TMC will establish an Administrative Core which will collaborate closely with its own Data Analysis Core and the SenNET Data Coordination Center (CODCC) to develop harmonious Standard Operating Practices, to generate data packages suitable for the development of the desired maps and atlases, to evaluate novel approaches (especially as developed by the Technology Development Projects) and to coordinate activities with other TMCs. More specifically, the Administrative Core will ensure that, in addition to completing the research goals outlined in their own applications, each team works collaboratively with all members of the Network to contribute to developing data and metadata standards, develop metrics for data generation, participate in cross-site studies, engage in cross-training, and guide development of data analysis and visualization tools that can be used by the broader scientific community.

    Because NIH expects to develop atlases of as many tissues and conditions as possible, applicants should be cognizant that a subset of proposed Tissue Mapping Centers may be funded based on programmatic priorities, and that multiple TMCs may be expected to work closely together around large, complex organs or systems.

    Background and Objectives of the Cellular Senescence Network (SenNET) consortium:

    Cellular senescence was initially described by Hayflick and Morehead in 1961, but remained relatively understudied for the next 3 decades, as senescence was originally thought to be an in vitro phenomenon. However, starting in 2001, work by multiple groups showed that senescent cells can negatively affect their local tissue environments through multiple pathways including the Senescence-Associated Secretory Phenotype, or SASP. The subsequent finding that these cells are found in vivo and are more abundant than previously thought led to the development of genetic and pharmacologic methods to manipulate or remove senescent cells. Importantly, removal of senescent cells in adult mice led to significant improvements in both healthspan and lifespan.

    These advancements have resulted in significant interest in the development of senolytics, drugs that can preferentially eliminate senescent cells. However, several issues need resolution before interventions to remove senescent cells are tested in humans. For example, while excessive accumulation of senescent cells is associated with deleterious late-life effects including accelerated aging and increased susceptibility to chronic diseases such as atherosclerosis, cancer, cardiac dysfunction, kidney dysfunction, neurodegeneration, pulmonary fibrosis and many others, senescent cells also serve beneficial roles during tissue remodeling in embryogenesis, as well as during parturition and wound healing. In addition, their role as a tumor protection mechanism is also well established. 

    Progress in the past few years has also indicated a large heterogeneity in senescent cells’ characteristics depending on the inducing agent or pathway, the cell type and tissue, and life stage. Similarly, the SASP appears as heterogeneous as the cells from which it is derived. Therefore, understanding the mechanisms that distinguish beneficial from deleterious senescence and the heterogeneity underlying senescent cell states are critical knowledge gaps. As the science progresses, it is clear that a “one size fits all” for the development of senolytics that only remove deleterious without touching beneficial senescent cells is not realistic, and a detailed characterization of senescent cell states and their associated SASP is an urgent need.

    To address the knowledge gaps noted above, the NIH intends to support a Cellular Senescence Network (SenNet) which will identify biomarkers and construct tissue maps and atlases that describe multidimensional parameters of senescence across diverse tissue environments at molecular, cellular, and morphological levels and over longitudinal time frames.  The SenNet effort builds upon and extends existing single cell tissue mapping efforts including the Human Tumor Atlas Network, Human Biomolecular Atlas Program, and Human Cell Atlas. Together with the SenNet program, these efforts will continue to generate important resources for the scientific community that will inform future research and, ultimately, clinical decision-making. While the current RFA is focused only on human tissues, the ultimate goal of the SenNet is to construct maps and atlases of cellular senescence across multiple tissues, in response to multiple inducers and modifiers, in both health and disease, and in both mice and humans. The SenNet will be comprised of Tissue Mapping Centers (this RFA), Technology Development Projects (solicited under RFA-RM-21-009), and a Consortium Organization and Data Coordination Center (CODCC, solicited under RFA-RM-21-010). 

    Goals of the Tissue Mapping Centers (TMC) of SenNet:

    Research Objectives

    As part of that overall effort, this FOA seeks to establish state-of-the-art Tissue Mapping Centers (TMCs) that will generate high-resolution, multi-parameter biomarkers and maps of cellular senescence in healthy human organs and tissues as a central goal. The SenNet is specifically focused on human tissues, with an emphasis on healthy tissues under a variety of conditions; as such, work on animal models or diseased tissues will be accepted only when well justified and as needed to support the primary/central goal. TMCs will use these maps, in coordination with the Consortium Organization and Data Coordination Center (CODCC), to generate a comprehensive atlas and provide new insights into the heterogeneity as well as common features of cellular senescence across tissues under various physiological conditions, including changes across the lifespan.

    Each TMC is expected to focus on at least 2 human tissues and their relevant biofluids, and it is expected that by the end of the 5 years of funding, the consortium as a whole will provide a broad set of maps across multiple tissues and under various conditions. All TMCs will be funded as Cooperative Agreements, and the NIH will exercise discretion and selective funding in order to ensure a comprehensive coverage of tissues.

    Tissue Mapping Center Organization

    This FOA uses the multicomponent U54 mechanism. Each TMC will be composed of 4 Cores: Administrative, Biospecimens, Biological Analysis and Data Analysis. A minimum of two tissues and their relevant biofluids need to be proposed, but applicants may propose additional tissue-specific projects. Applicants are encouraged to consider staggering the introduction of these projects based on prior experience, preliminary results, resources and personnel, and synergy with other projects. Each Core should have a well-defined and distinct function as described below and be synergistic without being highly inter-dependent. The different Cores may vary in size, start date and composition depending on the needs of the project, but should be integrated to achieve the overall goal of the TMC. The proposed budget should reflect the needs within each funding year. A scale-up model after the setup phase might be proposed, based on the number of organ specific projects, and as consortium activities begin.

    Administrative Core

    Successful applicants to this funding opportunity announcement will become members of the larger SenNet, composed of investigators who have been funded in response to at least one of the three SenNet FOAs. All projects within the SenNet will be funded as Cooperative Agreements, so that NIH staff will have a significant role in shaping the scientific aspects of the project. Each TMC will establish, during the first year of the award, an Administrative Core which will collaborate closely with its own Data Analysis Core and the SenNet Data Coordination Center (CODCC) to develop harmonious Standard Operating Practices, to generate data packages suitable for the development of the desired atlases, to evaluate novel approaches (especially as developed by the Technology Development Projects) and to coordinate activities with other TMCs. More specifically, the Administrative Core will see that, in addition to completing the research goals outlined in their own applications, each team works collaboratively with all members of the Network to contribute to developing metrics for data generation and metadata standards, participate in cross-site studies, engage in cross-training, and guide development of data analysis and visualization tools that can be used by the broader scientific community.

    The Administrative Core as led by the contact PD/PI of the TMC must demonstrate experience in managing large multi-disciplinary teams involved in tissue mapping and atlas construction, or related expertise. The primary responsibilities of the Administrative Core include coordinating various components of the TMC, coordination with other TMCs, and facilitating communication and coordination with the SenNet CODCC to ensure timely submission of data collected in accordance with the agreed Standard Operating Procedures (SOPs) and Common Data Elements (CDEs) as approved by the SenNet Steering Committee.

    Data generation, quality assessment and submission of data and metadata by each TMC will be assessed by the Executive Committee of the Sen Net for meeting goals and milestones at two-time points: 1) the point at which data passes internal and agreed-upon Quality Control (QC) metrics and is accepted for ingestion by the CODCC; and 2) At the time of release of the data to the community by the CODCC.

    Biospecimen Core

    The primary objective of the Biospecimen Core is the collection and processing of tissue samples to be used in constructing the proposed maps and atlases according to the standards established by the Steering Committee of the CODCC. Applicants must have access to high-quality, well-annotated human samples from non-chronically diseased individuals with appropriate diversity in gender, race, socio-economic status and other relevant diversity parameters. Preference will be given to applicants having access to longitudinal data. While the NIH recognizes that a statistically significant analysis of variability among multiple samples with the stated criteria might not be achieved within the timeframe of the award, it strongly encourages the inclusion of as much diversity as possible, so that the maps and atlases capture this heterogeneity, as well as commonalities among groups.

    The types of biospecimens collected, including clinical pathology when relevant, the frequency and the methodology used will depend on the specific types of analyses to be performed, but at least will conform with Standard Operating Procedures established for the network as a whole during the first year of the project. In order to maximize the utility of data generated by the Consortium, TMCs are strongly encouraged to establish consents during the setup phase that (a) explicitly allow open (non-restricted) data sharing and (b) allow sharing samples with other SenNet-funded groups, as well as other NIH-funded projects of related scope.

    The leadership of the Biospecimen Core is responsible for ensuring relevant expertise and the Core should develop specific, quantitative, annual milestones for collecting, processing, annotating, and classifying biospecimens. As for the Administrative Core, biospecimen collection, preservation and quality management will be assessed for meeting goals and milestones established by the Steering Committee of the CODCC.

    During the setup phase, TMCs are encouraged to start by optimizing their pipeline by focusing on one tissue or component of an organ system, while actively planning for expanding to more than one tissue during the scale-up phase. Applicants must be able to perform comprehensive characterizations of the quality of human biospecimens at high resolution and describe plans for biospecimen management and minimization of tissue degradation. With the introduction of each new tissue and organ, the TMCs should take the lead for establishing best practices for collection and preservation of that tissue. The Biospecimen Core of each TMC will work closely with similar Cores from other TMCs, as well as other groups working on similar challenges, such as the Human Tumor Atlas Network (HTAN), Human Biomolecular Atlas Program (HuBMAP) and Human Cell Atlas (HCA). The Biospecimen Cores of the SenNet will establish best operating practices for biospecimen management throughout the Network. Tissue Mapping Centers are strongly encouraged to plan a prospective collection strategy, including collection of appropriate epidemiological, socioeconomic and anatomical data alongside data on specimen collection. Tissue Mapping Centers are strongly encouraged to identify robust biological and statistical rationales for sampling decisions from human donors, for example whether to focus on intra-individual sampling, inter-individual sampling or temporal sampling across the lifespan. The TMCs will implement accepted best practices for collection and preservation of tissues, adapting them as needed for Network-wide use. Tissue Mapping Centers are strongly encouraged to develop enrollment criteria that will minimize the risk of abnormal or degraded tissue and pursue broad donor consent for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data. Limitations in donor consent will be considered a hindrance to the entire project and might disqualify applicants from funding. Teams are encouraged to present a strong scientific justification for their choice of tissues and to consider availability of high-quality tissue and matching technical expertise on specific tissues. Applicants are also encouraged to consider Ethical, Legal and Social Issues (ELSI) of tissue collection and to consider return of results to donors or their families.

    Some of the challenges that the core will need to address include:

    • Developing a clear and common protocol on how to collect tissues, or if it is a repository, collect all metadata and information on how the tissue was collected;
    • Identifying availability of tissues from healthy donors, especially tissues not readily collected in routine schedules. Fresh tissue is preferable for single cell analysis, but the possible use of rapid autopsy, donors and biobanks should be explored;
    • Capturing and preserving senescent cells in tissues and under conditions where these cells are rare, such as in young healthy donors;
    • Optimizing among all TMCs the best operating practices for pre-analytical processing of tissues;
    • Characterizing and minimizing degradation of tissue during collection, pre-analytical processing, storage and shipping;
    • Collecting biospecimens and experimental metadata in a consistent and interoperable format using existing, established ontologies and standards where appropriate;
    Biological Analysis Core

    The primary objective of the Biological Analysis Core is to provide high resolution state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of identifying robust biomarkers of senescence, and constructing the maps that will contribute to building the atlases from the tissues under study at the cellular, microenvironment and secretome levels. The Biological Analysis core will generate high resolution, high content, high-throughput biomolecular data to generate maps of cellular senescence in non-diseased human tissues, organs and organ systems. For this purpose, a high-resolution assay is defined as one that can reliably and reproducibly assign detected biomolecules to individual cells or extracellular compartments of a tissue. A high content approach is one that maximizes identification of senescent cells, their environment and/or their secretions through a combination of biomolecular depth, spatial resolution and multiplexing of complementary, multi-parameter assays. A high throughput pipeline is one that maximizes the bandwidth of data production to result in any or all of the following: 1) accelerated speed of analysis, so that hundreds or thousands of samples can be analyzed at once, 2) greater depth of analysis, so that hundreds or thousands of molecules can be analyzed in a single sample, or 3) enhanced capacity for volume, so that a given set of molecules can be analyzed in all the senescent cells within a larger tissue sample. Approaches that maximize the volume of tissue that will be analyzed while maintaining cellular resolution and high biomolecular content are strongly encouraged.  

    The Core will be responsible for generating high quality biomarkers and maps using multiple assays for at least two organs and their relevant biofluids, but a TMC can propose additional tissues. The responsibilities of the Biological Analysis Core include establishing and optimizing SOPs for the collection of relevant metadata including validation and benchmarking of assays; and generating high quality, high-content data using multiple assays with metrics for data quality control, reproducibility, and normal variation. Assays should be capable of high-resolution, state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of constructing multi-scale, multi-dimensional maps. These Cores are expected to work with the Biospecimen Cores to set up a framework for collecting high quality biospecimens in a consistent manner from human subjects, possibly including biobanks, as well as surgery and early autopsy materials, and should provide a strong rationale for the sampling approach and collection of appropriate metadata that will enhance the utility of data.

    The Biological Analysis Core will also work closely with the Data Analysis Core on topics such as providing data in consistent formats, with sufficient metadata describing the origin and nature of the biospecimen, details of collection and pre-analytical processing, details of the assays performed, and any filtering of the data performed prior to submission to the central CODCC. The Biological Analysis Core needs to be flexible in their data collection strategies such that new technologies introduced through technology development projects, or related atlas-building projects might be quickly tested, validated and adopted over the course of the award lifetime.

    Each team will characterize senescent cells, their environment and corresponding Senescence Associated Secretory Phenotype (SASP) at the organ, tissue and single cell levels in at least 2 human tissues/organs, as well as relevant biofluids, with respect to:

    • Developmental stage of the donor
    • Physiological status
    • Aging
    • Sex and gender
    • Nature of the cellular senescence inducer, if appropriate
    • In response to cellular senescence-targeted interventions

    The Biological Analysis Core will have several components, including but not limited to:

    • Biomarkers. The primary objective will be to develop comprehensive, dynamic, and searchable sets of biomarkers of cellular senescence, including both cellular and secretome aspects, in the tissues under investigation.
    • Models. The goal is to develop innovative models to study cellular senescence and the SASP, including the development of human ex vivo approaches such as explants, artificial organoids and 3-D cultures, as well as non-human animal models.
    • Perturbations. The TMC will explore how perturbations of cellular senescence affect different populations of senescent cells. Perturbations include different inducers, as well as senolytics, senomorphs, immune therapies and others. In some cases, these studies are likely to require experimentation in mice or other non-human models.
    • Imaging. The goal will be to develop 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.
    • Computation. Deep analytical capabilities in computation and Artificial Intelligence are expected to facilitate data analysis as well as the development of predictive mathematical models. A strong computational capability is expected to be part of both the Biological Analysis Core and the Data Analysis Core.

    In addition to single cell analysis using dissociative techniques, Biological Analysis cores are expected to be able to characterize the spatial distribution of a significant number and variety of biomolecules using established techniques such as FISH, immunofluorescence and RNAseq, and are strongly encouraged to incorporate, optimize and validate emerging in situ assays that will generate complementary quantitative, high-content, high-throughput biomolecular data.

    Some of the key challenges that the Biological Analysis Core is expected to address include but are not limited to:

    • Adapting single cell technologies to cells that are large and fragile;
    • Integration, automation, benchmarking and validation of imaging and omics assays;
    • Characterizing and reducing technical variation of common assays between TMCs;
    • Adapting appropriate quality control practices, such as identifying and analyzing missing, incorrect or sparse data;
    • Identifying and analyzing neighborhoods and microenvironments in tissues;
    • Annotating and interpreting data with common ontologies by identifying cell type, state and spatial interactions between cells, and with their extracellular environments;
    • Using molecular characteristics to infer time-dependent and space-dependent phenotypes and functional states, to establish the diversity of quiescence and senescence states;
    • Collecting and analyzing tissue to understand the degree of organizational variability in the same tissue from different individuals or multiple tissues from the same individual;
    • Establishment of collaborative arrangements to ensure the data produced are compatible, harmonized, and interoperable with other NIH-funded efforts focused on single cell analysis or other relevant technologies and assays.
    Data Analysis Core

    The primary objective of the Data Analysis Core is the construction of the biomarker and map datasets produced by the individual TMC and delivering the data to the SenNET Consortium Organization and Data Coordinating Center (CODCC.) The Data Analysis Core will be responsible for data annotation, curation, and analysis. It will be responsible for building maps from the data generated by the Biological Analysis Core, including the registration of the data with respect to biological characteristics of the subject, sample preparation, analyses, identification and annotation of cell types and states and extracellular compartment, and preparing different datasets for sharing with the CODCC, to enable it to build final atlases in the context of the entire SenNet.

    The Data Analysis Core should include a robust computational capability and is strongly encouraged to use existing software packages and analysis methods that would enhance rigor, reproducibility, and usability. The Data Analysis Core will also work closely with the other TMCs and the CODCC to develop and implement Network-wide open data and metadata standards; data quality metrics, ontologies and data elements; integration of imaging and omics data; and analytical tools for visualization, segmentation and annotation.

    Roles of the Data Analysis Core include ensuring that data is collected and submitted to the CODCC conforming with the agreed practices and principles of the Network, including Standard Operating Procedures (SOPs), Common Data Elements (CDEs) and the Network's data sharing policy. In addition, each individual Data Analysis Core will be responsible for cross-validation of assays within and across TMCs and interpretation of data generated by that TMC. Importantly, the Data Analysis Core will design and conduct at least one preliminary study illustrating how the resulting tissue dataset could be utilized to build an atlas and establish a set of biomarkers (the deliverables).

    Other TMC Application Considerations

    There are a number of additional issues that applicants should consider when crafting their applications.  These include: 

    TMC applicants are encouraged to read the Technology Development Projects (RFA-RM-21-009) and the Consortium Organization and Data Coordination (RFA-RM-21-010) RFAs for more information regarding other aspects of the SenNet consortium.

    Governance of the SenNet: The awards funded under this FOA will be cooperative agreements (see Section VI. 2. Cooperative Agreement Terms and Conditions of Award). Close interactions among the awardees and NIH will be required to maintain this complex program. All components will be governed by the SenNet Steering Committee (see Section VI: Terms and Conditions of Cooperative Agreement).

    Performance Requirements: Meet yearly milestones as defined by investigators and NIH Program Official at the time of award. Work with, cooperatively interact with, and actively seek input from NIH.

    Evaluation of the Program: As the efficiency of the funded research is an important priority for NIH, representatives from all award projects will be expected to participate in an external evaluation process of the SenNet coordinated by NIH Program Staff (see Section VI: Terms and Conditions of Cooperative Agreement.)

    Incomplete Applications

    The following types of applications are incomplete and will not be reviewed.

    Applications that do not address all sub-sections described in the Research Strategy instructions (see Section IV.2: Content and Form of Application Submission - PHS 398 Research Plan).

    Non-responsive Applications

    Applications addressing the following topics will be deemed non-responsive and will not be considered for review:

    • Projects primarily focused on mechanistic studies aimed at understanding biological processes, but that will not result in the generation of a comprehensive map and atlas;
    • Projects proposing maps and atlases constructed using solely non-human samples or human biospecimens with diseased or dysfunctional characteristics;
    • Projects proposing maps and atlases based upon a single experimental assay (i.e. a map or atlas constructed from a single data type);
    • Projects that do not propose all the required components of the TMC organization described below;
    • Projects that fail to focus on cellular senescence as currently defined in the field, and characterized by at least some of the accepted parameters such as SA-bGal or p16 expression, SASP production, or proliferation arrest.

    Projects with restrictive patient/donor consent forms that will hinder broad sharing of data and specimens.

    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.

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

    Section II. Award Information
    Funding Instrument

    Cooperative Agreement: A support 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 FOA.

    Application Types Allowed

    New

    The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.

    Clinical Trial?

    Not Allowed: Only accepting applications that do not propose clinical trials

    Need help determining whether you are doing a clinical trial?

    Funds Available and Anticipated Number of Awards

    The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

    The NIH Common Fund (Office of Strategic Coordination) intends to commit $18M Total Costs per year to fund up to 6 awards. The awards are contingent upon NIH appropriations and the submission of sufficiently meritorious applications.

    Award Budget

    Application budgets are not limited but need to reflect the actual needs of the proposed project.

    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 FOA.

    Section III. Eligibility Information
    1. Eligible Applicants
    Eligible Organizations

    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:

    o   Hispanic-serving Institutions

    o   Historically Black Colleges and Universities (HBCUs)

    o   Tribally Controlled Colleges and Universities (TCCUs)

    o   Alaska Native and Native Hawaiian Serving Institutions

    o   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)

    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)
    • Eligible Agencies of the Federal Government - NIH Intramural Program
    • 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 Institutions

    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  allowed.

    Required Registrations

    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.
    • o   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.

    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 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.

    An investigator designated as the Contact PD/PI or MPI of an application under this FOA must not be the designated Contact PD/PI of another application under the companion SenNet FOAs RFA-RM-21-009 and RFA-RM-21-010.

    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.  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 NOT-OD-11-101).

     

    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:

    Felipe Sierra
    National Institute on Aging (NIA)
    Telephone: 240-338-9544
    Email: sierraf@nia.nih.gov

    Page Limitations

    Available Component Types

    Research Strategy/Program Plan Page Limits

    Overall

    12

    Admin Core

    6

    Biospecimen Core

    6

    Biological Analysis Core

    12

    Data Analysis Core

    6

    Additional page limits 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, Minimum1, maximum 1
    • Administrative Core: Minimum 1, maximum 1
    • Biospecimen 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 Location(s) (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 & 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.  The budget must include at least the following elements:

    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.

    TMC Program Manager: Based on the complex roles the TMC will play within the SenNet, the TMC PD(s)/PI(s) are strongly encouraged to propose and budget for a TMC 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 TMC 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 TMC 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 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)

    Introduction to Application: N/A

    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 TMC. Describe the vision and goals of the TMC 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 TMC 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 TMC activities for SenNet and the wider research community. Provide goals and milestones for the entire TMC. The applicant must provide a detailed description of the TMC'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 TMC, its goals and objectives, and background information to provide feasibility of accomplishing these goals.  Explain the rationale for tissue/organ selection, innovation and synergy between the tissues and organs chosen, and the assays deployed. Describe the timeline for the TMC, 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 TMC 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 donors. In addition, propose a plan for coordination and collaboration within the Consortium, with other TMCs and CODCC. Describe synergies and possible collaborations with other initiatives or the wider research community that would enhance the productivity of the TMC.

    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 TMC, 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 should 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 TMC and how the different components of the TMC will interact to achieve these goals. Specifically, applicants must provide a timeline with milestones and details of how the TMC 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 TMC and its goals. The parent institution is expected to provide documented evidence of space dedicated to the needs of the TMC, protected time to devote to TMC activities, staff recruitment, dedicated equipment, or other financial support for the proposed TMC. Both the parent institution and pertinent departments should provide assurance of their commitment to the TMC.

    If collaborative linkages are being developed between the TMC 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, should 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, taking all steps needed to protect the information, and take other steps to protect the information of research participants. Applicants should 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 should 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.

    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.   

    PHS Human Subjects and Clinical Trials Information (Overall)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

    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).

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

    PHS Assignment Request Form (Overall)

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

    Administrative Core

    When preparing your application, use Component Type ‘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)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Administrative Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Administrative Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Administrative Core)
    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.   
    Budget (Administrative Core)

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

    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 TMC 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.

    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 (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 administrate and coordinate the Center's activities:

    Leadership Plan: Describe the leadership team and how components of the TMC, including key personnel, will interact within the TMC 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 TMC and participation in Network activities such as teleconferences, development of SOPs etc. Describe plans for soliciting, selecting, reviewing, and administering pilot projects. Describe how synergy and integration within the TMC and with the other TMCs will be fostered. The parent institution should provide assurance of its commitment to continuing support of the TMC 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 TMC organization including coordination and interactions between the different TMC 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 TMC. Describe plans for assessing progress of the TMC to meet its goals and milestones. Describe and, preferably, demonstrate through presentation of preliminary data strategies for how the components of the TMC 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 TMCs on topics including but not limited to SOPs, assay protocols, consent materials 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 TMC and its goals. If collaborative linkages are being developed between the TMC 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, should address a Data Sharing Plan. Applicants should 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 should 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 willbe 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.

    PHS Human Subjects and Clinical Trials Information (Administrative Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

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

    Biospecimen Core

    When preparing your application, use Component Type ‘Core.’

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

    SF424 (R&R) Cover (Biospecimen 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 (Biospecimen Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Biospecimen Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Biospecimen Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Biospecimen Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    Budget (Biospecimen 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 Biospecimen Core of the SenNet. For applications with multiple Core Leaders, a minimum effort of 0.8 person-month is required for the Contact PD/PI 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.

    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 (Biospecimen Core)

    Specific Aims: State the specific aims for the Biospecimen Core and the general approach to tissue collection, handling, storage, and distribution. A minimum of 2 tissues should be chosen, with rationale for choices and a plan for ramping up efforts.

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

    Tissue and subject selection: Provide a strong scientific justification for the choice of tissues, including availability as well as synergies with other initiatives, if applicable. Describe the level of access to a source of relevant human samples (i.e., ongoing clinical or observational trial, post-mortem samples, or other approved sources) immediately upon award. Describe the use of retrospective human samples, non-human tissues and/or alternative in vivo or ex vivo platforms such as organoids, patient-derived xenograft models, and other systems that maintain native architecture. Include a rationale for the selection of epidemiological and health characteristics. With a goal of defining commonalities within a collection of heterogeneous tissues, describe how the selection of subjects will favor diversity, through the inclusion of individuals of both sexes, and multiple ethnicities, races and socioeconomic status. Tissue Mapping Centers are strongly encouraged to develop enrollment criteria that will minimize the risk of abnormal or degraded tissue. Applicants are also encouraged to consider Ethical, Legal and Social Issues (ELSI) of tissue collection and, if appropriate, to consider return of results to donors or their families.

    Sample acquisition pipeline: Describe the type, volume, source, frequency, and sampling approach for human biospecimen collection, including biological, technical, and statistical power justification. Provide details of the number of samples, including tissue types and physiological status that can be acquired and processed each year. Tissue Mapping Centers are strongly encouraged to identify robust biological and statistical rationales for sampling decisions, for example whether to focus on intra-individual sampling, inter-individual sampling across the lifespan or temporal sampling. Describe how the Biospecimen Core will interact with other arms of the Network to establish Network-wide best-practices for collection and preservation of tissues, quality control practices, and assembly of specimen metadata for downstream interrogation and analysis. Describe quality assurance and quality control metrics that will be developed and/or employed to protect biospecimens from factors that could influence specimen integrity (i.e., temperature, humidity, light, structural quality) and to ensure high sample quality upon shipping.

    Pathological Characterization: While SenNet is focused on healthy tissue, correct ascertainment of tissue identity, pathological/healthy status and quality control require the establishment of appropriate pathological assessment. Describe the plans for establishing or utilizing a pathology unit, and how the unit will interact with the rest of the Biospecimen Core and the Biological Analysis Core.

    Informed Consent: Provide details about the breadth of informed consent to be obtained from donors; biospecimens will potentially be analyzed or re-analyzed later in the Network using new and cutting-edge assays and data tools that will be introduced after award so careful attention must be paid to the design of donor consent forms at the time of specimen collection, to allow for unrestricted sharing of data for research purposes. Consent forms that allow for the broadest possible data sharing are strongly encouraged, to maximize the utility of biospecimens and data. The strongest applications will have a broad data sharing consent, and conversely, restrictive data sharing plans will be considered as a negative feature of the application.

    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 TMC and its goals. If collaborative linkages are being developed between the TMC 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, should address a Data Sharing Plan. Applicants should 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 should 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.

    PHS Human Subjects and Clinical Trials Information (Biospecimen Core )

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

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

    Biological Analysis Core

    When preparing your application, use Component Type ‘Core.’

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

    SF424 (R&R) Cover (Biological Analysis 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 (Biological Analysis Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Biological Analysis Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Biological Analysis Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Biological Analysis Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    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 TMC, and it should effectively and efficiently contribute to the overall objectives of the TMC 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 tissues or organs chosen. A minimum of 2 and maximum of 4 tissues should be chosen, with rationale for choices and a plan for ramping up efforts.  

    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: Provide an overview of how the Biological Analysis Core will interact with the Biospecimen Core to collect and analyze biospecimens in a manner that reflects the expected tissue diversity, 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 TMC. 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 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 human ex vivo approaches such as explants, artificial organoids, 3-D cultures, or non-human animal models as applicable.

    Perturbations: Describe in detail how the TMC will employ perturbations 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. Discuss and justify perturbation experimentations to be conducted in mice or other non-human models.

    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 TMC and its goals. If collaborative linkages are being developed between the TMC 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, should address a Data Sharing Plan. Applicants should 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 should 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.

    PHS Human Subjects and Clinical Trials Information (Biological Analysis Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

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

    Data Analysis Core

    When preparing your application, use Component Type ‘Core.’

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

    SF424 (R&R) Cover (Data Analysis 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 (Data Analysis Core)

    Enter Human Embryonic Stem Cells in each relevant component.

    Research & Related Other Project Information (Data Analysis Core)

    Human Subjects: Answer only the ‘Are Human Subjects Involved?’ and 'Is the Project Exempt from Federal regulations?’ questions.

    Vertebrate Animals: Answer only the ‘Are Vertebrate Animals Used?’ question.

    Project Narrative:  Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

    Project /Performance Site Location(s) (Data Analysis Core)

    List all performance sites that apply to the specific component.

    Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

    Research & Related Senior/Key Person Profile (Data Analysis Core)

    ASSIST will default to “Project Lead”. If you would like to use a different category, then replace “Project Lead” below with a different Category (e.g., Core Lead).

    • ·    In the Project Director/Principal Investigator section of the form, use Project Role of ‘Other’ with Category of ‘Project Lead’ and provide a valid eRA Commons ID in the Credential field.
    • ·    In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
    • ·    Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
    • ·    If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
    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 atlases 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 TMC 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 TMC. State how these pipelines might be scaled to meet the demands of increased throughput within the TMC. 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 TMC, 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 TMCs and within the SenNet as a whole.

    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 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 TMC. As appropriate, describe how samples from the same individual or multiple individuals 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 TMC and its goals. If collaborative linkages are being developed between the TMC 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, should address a Data Sharing Plan. Applicants should 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 should 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.

    PHS Human Subjects and Clinical Trials Information (Data Analysis Core)

    When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) 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 a Delayed Onset Study record.

    Study Record: PHS Human Subjects and Clinical Trials Information

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

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

    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 field of 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 Core Leaders 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
    1. Criteria

    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.

    Overall Impact - Overall

    Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Center 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 Center proposed).

    Scored Review Criteria - Overall

    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 Center that by its nature is not innovative may be essential to advance a field.

    Significance

    Does the Center 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 Center 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 assays proposed essential to the mission of the TMC and the SenNet? Will the data and knowledge generated by this TMC provide sufficient metadata to create reliable high content maps of the tissues chosen? Do the applicants have a robust plan for sharing and dissemination of data produced by the TMC? Do the Cores contribute substantially to the overall objectives of the TMC?

    Investigator(s)

    Are the PD(s)/PI(s), collaborators, and other researchers well suited to the Center? 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 TMC 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 TMC and SenNet? Do the TMC 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 Center? Have 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?

    If the Center 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?  

    Specific to this FOA:

    Overall: If proposed for validation or perturbation studies, is the use of non-human models or diseased tissue well justified? Have issues of rigor and reproducibility been adequately addressed? Is the data sharing plan adequate to the needs of SenNet?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 TMC as they relate to achieving the overall objectives of the Network? 

    For the Biospecimen Core: Is there a plan for prioritizing and coordinating the dissemination of specimens within the TMC and with other TMCs? Is there a sound plan for procuring and storing high quality prospective biospecimen clinical and epidemiological information? Is there a strong scientific foundation for the multidimensional, multiparameter data collection proposed? Does the accrual of biospecimens match plans for data analysis? Will the proposed quality assurance and quality control plans facilitate successful molecular, cellular, and tissue level characterization of biospecimens?

    For the Biological Analysis Core: Is there a solid plan for interaction with the other components of the TMC, including the Biospecimen 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 TMC 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?  

    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 TMC, including mechanisms for internal quality control of ongoing research? Are the staffing, equipment, and other resources that are available to the TMC sufficient and relevant to meeting the goals?

    Additional Review Criteria - Overall

    As applicable for the Center 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 Center  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

    Additional Review Considerations - Overall

    As applicable for the Center 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

    Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

    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) Sharing Model Organisms; and 2) Genomic Data Sharing Plan .


    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 the Center for Scientific Review (CSR) 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:

    • 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.
    • Will receive a written critique.

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

    Applications will be assignedto the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

    • 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.
    • Compliance with NIH data sharing policy.
    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 the NIH 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.

    Awardees must comply with any funding restrictions described in Section IV.5. 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: Recipient 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 awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

    Prior Approval of Pilot Projects

    Awardee-selected projects that involve clinical trials or studies involving greater than minimal risk to human subjects require prior approval by NIH prior to initiation. 

    2. Administrative and National Policy Requirements

    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: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

    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.

    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 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

    Cooperative Agreement Terms and Conditions of Award

    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 Grants Policy Statement (which implements the aforementioned HHS Regulations (45 CFR Part 75),  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 awardees 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 resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees 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 TMC, 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 TMC 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 TMC a minimum of 1.2 person-months of effort per year for any investigator designated as an MPD/MPI of the TMC.
    • Serving on the SenNet Steering Committee. The SenNet TMC 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 TMC, 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, 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 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 TMC 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 TMC project, the Awardee, 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 TMC 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 TMC 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 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.

    Awardees will retain ownership of the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, 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 awardees in avoiding unwarranted duplications of effort across the SenNet.
    • Assisting the awardees as a resource in facilitating their broader interactions with other NIH programs to disseminate results, tools, and models from the TMC and take advantage of existing NIH resources and infrastructures. This will specifically include acting as a liaison between the TMC and other atlas-building programs.
    • Ensuring that the TMC 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 awardees (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, TMC 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 awardees 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 will be the main governing body for the SenNet. The Steering Committee will be composed of one representative (contact PD/PI or other senior level investigator) from each SenNet initiatives (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.

    Two PD(s)/PI(s), representing two different SenNet awards, will be selected to serve as chairpersons of the Steering Committee starting at the first meeting of the Steering Committee following award issuance. All SenNet Steering Committee decisions and recommendations that require voting will be based on a majority vote.

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

    The SenNet Steering Committee will:

    • Identify 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.
    • Review progress of the SenNet toward meeting the overall Network goals.
    • Ensure that all SenNet members utilize the resources developed by the SenNet CODCC, TMCs and Technology Development Projects.
    • Coordinate dissemination of Network output to the broader senescence research community.
    • Ensure that the Network takes advantage of existing NIH resources and programs.
    • Establish, as necessary, subcommittees to ensure progress of the individual Centers and the Network.

    In order for awardees to fully comply with NIH and consortium data sharing policies as detailed above, all awardees 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 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/ies to the Receiving Party/ies or thereafter becomes within the public domain other than as a result of disclosure by the Receiving Party/ies 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/ies; (c) is acquired by the Receiving Party/ies from a third party not under an obligation of confidentially; or (d) is hereafter independently developed by the Receiving Party/ies, without reference to the information received from the Disclosing Party/ies.  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 parties participation in the development and conduct of these programs, the parties 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.

    3. Reporting

    When multiple years are involved, awardees 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.

    The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later.  All awardees 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 $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement.  

    In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, 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 75 – Award Term and Conditions 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.

    Application Submission Contacts

    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: GrantsInfo@nih.gov (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: support@grants.gov

    Scientific/Research Contact(s)

    Felipe Sierra, Ph.D.
    National Institute on Aging (NIA)
    Telephone: 240-338-9544
    Email: sierraf@nia.nih.gov

    Peer Review Contact(s)

    Maqsood Wani, Ph.D.
    Center for Scientific Review
    Telephone: 301-435-2270
    Email: wanimaqs@csr.nih.gov

    Financial/Grants Management Contact(s)

    Jessi Perez
    National Institute on Aging (NIA)
    Telephone: 301-402-7739
    Email: jessi.perez@nih.gov

    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.

     

    Authority and Regulations

    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.

NIH Office of Extramural Research Logo
Department of Health and Human Services (HHS) - Home Page
Department of Health
and Human Services (HHS)
USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®


Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.