Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Funding Opportunity Title

Nuclear Receptor Signaling Atlas (NURSA): Hub (U24)

Activity Code

U24 Resource-Related Research Projects – Cooperative Agreements

Announcement Type

Reissue of RFA-DK-06-503

Related Notices

  • October 26, 2011 - See Notice NOT-HD-12-003. The purpose of this Notice is to revise the Funds Available and Anticipated Number of Awards section.

Funding Opportunity Announcement (FOA) Number


Companion FOA


Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)

93.847, 93.865   

FOA Purpose

The purpose of this FOA is to solicit applications for the Nuclear Receptor Signaling Atlas Hub (NURSA). The overriding goal of NURSA will be to significantly advance basic science findings to applications for human diseases and conditions for which nuclear receptors (NRs) play an integral role.  The organization of NURSA will consist of a Hub that is collaborative in nature by providing the integration and cohesion needed to aggregate, annotate, and present in a user friendly fashion state-of-the-art data from a series of collaborative research projects. The Hub will support a public web portal ( as part of a comprehensive approach to elucidating the role of NRs in normal physiology and disease. NURSA will assist in generating important new concepts and validated datasets that will provide the foundation for research leading to a more comprehensive understanding of the role of NRs in human physiology and metabolic disease. The NURSA Hub will integrate the work of investigators who will be funded through a series of NURSA Data Source Projects (NDSP). NDSPs will supply a steady stream of novel and cutting edge data derived from projects that will explore newly emerging opportunities in the NR field relevant to the missions of NIDDK and NICHD, and/or address key technological or conceptual roadblocks to progress. The Hub will foster annotation, and conversion to formats readily accessible by the broader community through the public web portal.

Key Dates
Posted Date

October 21, 2011

Letter of Intent Due Date

February 8, 2012

Application Due Date(s)

March 7, 2012

AIDS Application Due Date(s)

Not Applicable.

Scientific Merit Review

June/July, 2012

Advisory Council Review

October, 2012

Earliest Start Date(s)

December, 2012

Expiration Date

March 8, 2012

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Table of Contents

Part 1. Overview Information
Part 2. Full Text of 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 Nuclear Receptor Signaling Atlas (NURSA) is comprised of a collaborative and integrated network of investigators designed to advance our understanding of the role of Nuclear Receptors (NR) in health and disease. Moving forward NURSA will now center around a Hub consisting of an informatics resource and a community web portal to support a scientific agenda. Although NURSA has built a considerable amount of cohesion leading to significant advances, it is imperative that NURSA reach out to the broader community. Accordingly, the Hub will integrate the work of independent and experienced investigators through a series of peer reviewed NURSA Data Source Projects (NDSP). Together the Hub and NDSP investigators will constitute a consortium (NURSA). The Hub will provide the capability for data aggregation, annotation, and delivery in user friendly format for the wider community through a public web portal ( The NDSPs, and other affiliated projects, will serve as the development and research arm of NURSA, acting as the source groups for new and unique concepts and data. The Hub will seek to standardize descriptors across these groups, aggregating and annotating the data for public availability through the web portal. The Hub will provide the administrative support to facilitate the collaborative nature of NURSA. The Hub will: 1) develop and manage the informatics resource and a web portal (, 2) serve as the focal point for a program of research through a series of NURSA Data Source Projects (NDSP), 3) facilitate outreach by extending NURSA to the broader research community including assuring a steady flow of new data to the web portal from other investigators working on NRs, 4) work with NIH Staff through the cooperative agreement mechanism to establish effective governance, including integration of NDSPs, 5) manage, integrate and communicate data to the community, and finally, 6) organize and implement regular steering committee meetings and investigators’ retreats.

NURSA was initially funded by NIDDK, the NCI and the NIA ( with the goal to accrue, develop and communicate information about the Orphan Nuclear Receptor subfamily of Nuclear Hormone Receptors. Subsequent expansion included all NRs as well as relevant coregulators, ligands, and downstream targets. NURSA was re-competed in 2006 ( with co-sponsorship by NHLBI and NIEHS. NURSA has brought a collaborative approach to the generation of new research tools, reagents, technologies and concepts vital for developing an integrated understanding of the molecular regulation of nuclear receptors and associated coregulators as they impact human health and disease.  Among its accomplishments, NURSA has established comprehensive atlases of NR and coregulator expression in mouse and human tissues and cells ( NURSA has also developed an integrated multi-'omics discovery and hypothesis-testing/-validating platform that included often high throughput expression profiling and semi-quantitative proteomics and metabolomics analyses that ultimately developed a comprehensive base of knowledge of NR structure, function, and role in disease. Large datasets have been made publicly available through the web portal, in turn facilitating integration of data from many sources through the online molecule pages. NURSA has accelerated discovery in the areas of metabolism, cancer, aging, cardiovascular disease, response to the environment, and reproductive diseases and disorders. NURSA activities have allowed a more comprehensive understanding of the potential role for NRs in disease mechanisms and as targets for the development of novel approaches to therapeutics. NURSA now seeks to focus on translating the developed and accrued knowledge into deeper understanding of the roles played by NRs in human disease, including new and novel approaches to treatment.

Research Objectives

The overriding goal of NURSA will be to significantly advance translation of basic science findings to applications for human diseases and conditions for which NRs play an integral role. A multifaceted, interdisciplinary, coordinated and collaborative approach on several fronts will be required to generate the key reagents, assays, strategies and proof-of-concept studies required for the development of a more complete understanding of the role of NRs in physiology and pathophysiology of common and chronic diseases including diabetes, obesity, metabolic dysregulation, CVD, cancer, response to the environment, processes of aging, and reproductive diseases and disorders.  The basic NURSA platform has employed a high throughput integrated ‘omics approach (genomics, proteomics, bioinformatics, metabolomics) to discovery of NR and coregulator expression in specific tissues and cells, together with an understanding of the role of ligands as they impact target genes and gene networks. This has fostered a systems biology understanding of the underlying physiology and role in disease. NURSA now seeks to exploit this platform to catalyze movement toward a tissue and disease oriented understanding of the role(s) of NRs and coregulators in human disease.

The NURSA Hub will provide support for discovery and hypothesis-generating/testing research through two components: 1) an Informatics Resource/web portal, and 2) an integrated series of NURSA Data Source Projects (NDSP). The Hub will be publically available and open to collaborative interactions through the web portal ( and the NDSPs will be openly competed and peer reviewed.  The NSDPs will be integrated with the Hub to form the NURSA Consortium.  NDSP investigators will utilize the Hub resources for informatics support and will contribute to a constant flow of new data that will be integrated with the NURSA molecule pages. This new information will be made freely available through the community web portal. The Hub will provide the central support function of NURSA including data accrual, formatting and mining of the data, as well as administrative support and outreach.  The collaborative NDSPs will carry out the necessary studies to generate/translate new and accrued data into advances in understanding human health and disease. The use of the cooperative agreement mechanism will guarantee the integrated and collaborative nature of the consortium in partnership with the NIH.  The individual nature of the NDSPs through the cooperative agreement mechanism will lead to a NURSA team comprised of leaders in the field with equal stakes in the outcomes. The role of the Hub will be to perform many vitally important functions that contribute to the functional integrity and cohesive infrastructure of the consortium. The Hub will facilitate sharing of information with other consortia, databases, and scientific journals, as needed.  By providing basic administrative support for the consortium, the Hub will also facilitate management of the NURSA Consortium through a Steering Committee, interactions with an External Evaluation Committee, interactions with NIH Project Scientist(s) and Program Director(s), and outreach programs to the broader research community.

The Informatics Resource will be the support arm of the Hub, including data aggregation (from the NSDPs and other affiliated sources) and integration of projects brought forward through the NDSP and other outreach efforts. The Hub will provide the administrative structure to allow for integration of both components into an interactive consortium. A major outreach role for the Hub will be to work with the broader community as they and the NIH identifies cutting edge ideas to develop solutions leading to new advances. The NDSPs will ensure a source for discovery and data flow into the Hub. For example, data accrued at the Hub may provide the basis for a crucial question to be addressed by an NDSP project. Furthermore, data resulting from an NDSP could be assimilated directly into the Hub molecule pages for rapid dissemination.  The Hub will work with the collaborating labs to format the data for subsequent integration with other such data and with the NURSA molecule pages. The resulting data will be publicly available and searchable through the web portal. Understanding that there are many other sources of data that can be aggregated with the NURSA collection, the Hub will need to leverage existing public datasets to further enrich the information available through NURSA. The Informatics arm of the Hub will provide opportunities for collaborations with investigators independently funded by other means from which additional data can be sourced. To accomplish this goal the Hub will develop an outreach plan for accruing and aggregating data from individual investigators drawn from outside the consortium as well as relevant scientific journals. These goals will be achieved through outreach to potential users and stakeholders and could include collaborators drawn from research (e.g.  R-, or P-series) grants not initially a part of NURSA. Such projects may subsequently develop collaborative alliances with NURSA.

The Hub will replace the current NURSA structure but will continue to provide support for a consortium not only by maintaining the NURSA molecule pages, databases, and datasets, and the public portal (, but also the online public e-journal Nuclear Receptor Signaling. Responsibilities will also include participation in the continuing evolution and development of the evolving NIDDK trans-consortium data network (NIDDK Consortium Interconnectivity Network;, or its successor) that was developed with participation by NURSA. Through the Hub NURSA will adapt, develop and implement any software necessary for data handling and analysis, internet connectivity, and web services associated with dkCOIN. NURSA will support: 1) search tools for gene expression studies, 2) genome-wide profiling of epigenetic marks, 3) imaging-based datasets, 4) ligand structural repositories, and 5) new web interfaces that will allow data mining and meta-analyses across multiple databases, including those already housed at NURSA such as transcriptomine and the coregulator interactome. The Hub will facilitate sharing of information with other consortia, databases, and scientific journals, as well as potential outreach programs to the broader research community. An important role will be to establish data standards, analysis protocols, and metadata requirements for the integration of consortium investigators derived from the individual NDSPs, as well as any other associated projects identified through outreach efforts. 

Scientific Scope

The overriding goal of NURSA at this point will be to enhance the translation of in vitro and model organism (e.g. mouse) models of disease to human disease. Core questions to be addressed, including for NDSPs, that help to define the central focus may include but are not restricted to:   

1.            Can mouse models involving tissue specific knock-in or knock-out of NRs give reliable and testable predictions about human disease?         

2.            Can human iPSC’s be used to model NR actions in and development of disease?

3.            How do NRs recruit different and specific coregulator complexes in response to different signals (e.g. environmental cues, or ligands) to give specific and selective physiological or pathophysiological outcomes? Does transient interactome formation in response to a particular NR signal form a tissue or cell specific epigenome leading to a specific physiological or pathophysiological outcome?

4.            For a given NR signal, are there characteristic metabolic outcomes that are predictive of human disease?

5.            Can chemical biology tools and approaches be used to identify new therapeutic targets with the necessary selectivity and specificity to be pursued as novel pre-therapeutic leads for diseases where NRs are implicated and possibly help to identify new biology?    

NIDDK, through the Division of Diabetes, Endocrinology and Metabolic Diseases, is interested in how NRs impact metabolic diseases, including obesity, diabetes, NASH, osteoporosis, and dysregulated carbohydrate/lipid metabolism contributing to the metabolic syndrome. Emphasis is on translation of in vitro and model organism studies to human tissues and diseases. Examples include how NRs contribute to pathophysiology in key metabolic tissues, including adipose, liver, skeletal muscle, and the macrophage-adipose or -liver dynamic. Specifically the genomic and/or temporal and tissue-specific expression of NRs, related transcription factors, coregulators, and chromatin remodeling factors as they impact the cellular epigenome are key questions that can be addressed in high throughput fashion where integration of multi-‘omic and informatics analyses can help to pinpoint pathways central to disease development, progression, and treatment often through discovery-based studies that can be validated through hypothesis-generation and –testing in human tissues.

NICHD has recognized that it is now increasingly evident that several diseases and disorders of reproduction such as polycystic ovary syndrome (PCOS), endometriosis and leiomyoma may be due, at least in part, to alterations in sex steroid signaling pathways necessary for normal responsiveness of various components of the hypothalamo-pituitary-gonadal-reproductive axis.  Moreover, variants of NRs important for sexual development such as Steroidogenic Factor-1 (SF-1, NR5A1) may be associated not only with disorders of sex development such as primary adrenal failure, gonadal dysgenesis and hypospadias, but with primary ovarian insufficiency, male factor infertility and endometriosis as well.  Therefore, this FOA may provide the NICHD with an opportunity to pursue the underlying etiologies of the aforementioned conditions as they relate to the NR interactome with the ultimate goal of identifying novel strategies for prevention, diagnosis and treatment of these conditions.

Functions of the Hub:

In order to carry out this scope the successful applicant will present a strategy and plan to fulfill all responsibilities, functions and activities required of the NURSA Hub, including:

Informatics Resource:

To maintain currency and relevancy NURSA requires an influx of data that can be integrated with the molecule pages and serve to inform new ideas and concepts. The NDSP projects will serve as one arm of that task. These new projects from established investigators will serve as the research arm of the Hub. The Hub Resource must have a state-of-the-art capacity to handle new and emerging forms of high throughput (HT) data for NRs. The Informatics arm of the Hub will need to establish a strong presence through expertise in analysis, annotation, and web design. This will include adapting, developing, and deploying the necessary tools for the aggregation, annotation, and presentation of data such as that obtained from (e.g.) qPCR, next generation sequencing, epigenomic, metabolomic studies, image analysis and others, as needed.  The Hub will ultimately need to develop or adapt tools for (e.g.) the analysis of genome-wide profiling of epigenetic marks as they apply to NR signaling and function so that comparisons can be made across different cells and tissues. The Hub will seek to standardize approaches for data validation and presentation. Tools to analyze such data may include cistrome and proteome pipeline analysis suites, cytoscape, and others. The Hub will develop and provide the capability for users to mine the data displayed, as raw or filtered data sets or as components of the NURSA molecule pages. The aim will be to provide a valuable service to help catalyze the formation and testing of new hypotheses about NRs and their roles in disease. The NURSA Steering Committee will determine final policies regarding access to these Hub resources.  It is not the intention of NURSA to have the informatics resources reserved for the exclusive use of any one individual or project.

Management of the data will likely require database tools including relational databases. Public access may require an expanded user-interface to allow for various types of queries. NURSA will need to provide solutions proposed for database schemas and user-interfaces and be flexible and adaptable enough to build new and required features following the initial deployment. Any proposed solution must clearly demonstrate that such flexibility exists or can easily be added after the initial deployment.

Maintain and update the NURSA webportal:

Key functions of the NURSA webportal include access to and sharing of databases, information about reagents and ideas between NURSA members as well as the scientific community at large. The NURSA molecule pages represent the results of significant annotation and curation efforts for studies conducted by NURSA, and other, investigators. The development of search tools for genes, their transcripts, and their profiles in expression studies, including the transcriptomine module, have been made freely available through the web portal. Similar efforts have resulted in accrual of information about the coregulators that contribute to the NR interactome. Complex cellular imaging datasets reflecting gene expression patterns or transient signaling events are also likely to be generated. New tools and annotation protocols will have to be expanded, developed or adapted so that information can be retrieved and analyzed across datasets that are different by nature and accessible through the web portal. Likewise, NURSA will have to develop appropriate search and analysis tools that can lead to analyses between NURSA-generated data collections and other relevant databases available through the linked sources, as well as new interfaces that can allow the seamless sharing of data with other NIH-sponsored consortia particularly through dkCOIN, or its successor. NURSA has also developed and maintained a strategic alliance with The Endocrine Society, a professional scientific society and its signature journal, Molecular Endocrinology. These activities will continue and include reciprocal curation of relevant published papers, and archiving of datasets.  Strategic alliances with other relevant scientific journals will be considered and implemented if mutually beneficial. The Hub should provide a maximally efficient means for data collection, storage, and availability, from a variety of sources, and ensure that designs are adaptable, extensible and portable. Consideration should be given to development within a cloud computing environment to enhance long-term support for the data. A mix of existing and newly developed tools should be considered, including the development, acquisition, and implementation of any needed software, middleware, network interface, web services, and data storage. The Hub must demonstrate flexibility in the design principles of the user-interface as well as the underlying software infrastructure and thereby support the simplest to the most sophisticated tasks. Most queries will be simple, single query searches, followed up with finding the most interesting related molecules, pathways or datasets, and including data mining of related databases such as those presented by NCBI of the National Library of Medicine ( These requirements may imply that the proposed user-interface solution incorporate plug-ins or other similar approaches. The database schema should be available to the community and should be supported by a clearly documented API.

Facilitate interactions with other investigators, centers and consortia as part of an outreach effort:

Outreach has been a hallmark of NURSA and has included Pilot & Feasibility studies, Collaborative Bridging Projects, as well as recruitment of affiliated members as part of a broader Consortium. To ensure continued influx of new ideas, data, and investigators, NURSA will utilize a competitive and peer reviewed mechanism to recruit NURSA Data Source Projects (NDSP). These projects, funded for 2-5 years as subcontracts from the Hub will address difficult issues, roadblocks, unique opportunities or emerging questions in the NR field and solicit novel and innovative ideas for which the NURSA mulit-'omics discovery platform may be well suited. NDSP topics will seek to explore the cutting edge, including high risk/high gain ideas-all relevant to NRs and the mission of NIDDK ( and the interests of NICHD. Outreach to the broader community will seek to include leading investigators in the field willing to share expertise, data, and resources in return for affiliated membership in a new NURSA Consortium.  The web portal, including the e-journal Nuclear Receptor Signaling, will serve as the vehicle for dissemination of information, including datasets, and new/novel concepts.  The Hub will also contribute to collaborations between NURSA and other relevant NIDDK or NIH sponsored projects to facilitate broader sharing of data and resources, including through the NIDDK Consortium Interconnectivity Network (, or its successor. Such interactions may include both joint scientific events and integration of research databases. A continuing outreach effort by NURSA will also require developing a means for identifying and querying key stakeholders and users of its content as it seeks to accrue and communicate information and concepts to the broader research community, including other useful publically available datasets. The Hub will be responsible for defining and displaying online definitive policies regarding inclusion as a member of the consortium, PI roles and responsibilities, and the NURSA data sharing policy. 

Management of the consortium:

To facilitate new discovery essential to continued progress, the Hub will manage competitions for the NDSPs, integrating these into the consortium. The Hub will be responsible for broadcasting availability as well as for administrative handling of NDSPs.  However, the NIH, in consultation with a wide range of experts, will play an important role in defining the topics to be considered in the open competitions. NDSP investigators must agree to comply with NURSA policies regarding data sharing and availability. PD(s)/PI(s)s for the NDSPs will be funded for 2-5 years at up to $150,000 (T/C) per year and must provide milestones to be evaluated yearly. The NIH will identify a panel of External Experts not associated with NURSA to assist in topic identification and peer review. The Hub will be responsible for instituting a Scientific Project Online Tracker (SPOT) program, such as has been used by the NIDDK Beta Cell Biology Consortium (see BCBC; to assist in receipt and administration of NDSPs. The Hub will serve as the portal through which the solicitations for NDSPs will be conducted. A timeline should be provided for the solicitation, review, and funding of NDSPs. The Hub will need to initiate the first competition for NDSPs coincident with onset of NURSA funding. The Hub will also be responsible for the annual investigator retreat and EEC meeting.

Governance and Leadership Plan

Applications to this FOA should include a plan that defines the overall governance and organizational structure of the NURSA consortium. Included should be plans for formation of a steering committee, to be comprised of the PD(s)/PI(s) of the Hub, the NIH Project Scientist and the PIs of NDSPs. In addition consideration of a projected affiliated membership, regular meetings, SC actions, and roles in governance of the cooperative agreement should be described. More than one PD(s)/PI(s), or multiple PD(s)/PI(s), may be designated on the application for projects that require a team science approach that clearly does not fit the single-PD(s)/PI(s) model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD(s)/PI(s) on individual research projects is available at: for instruction).

Applications designating multiple PD(s)/PI(s) should include a section of the research plan, entitled Multiple PD(s)/PI(s) Leadership Plan (Section 12 of the Research Plan in the PHS 398). A rationale for choosing a multiple PD(s)/PI(s) approach should be described. The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PD(s)/PI(s) and other collaborators.

If budget allocation is proposed, the distribution of resources to specific components of the project or the individual PD(s)/PI(s) should be delineated in the Leadership Plan. In the event of an award, the requested allocations will be identified in the Notice of Award (NoA).

Section II. Award Information
Funding Instrument

Cooperative Agreement

Application Types Allowed


The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NIDDK intends to commit $1,500,000 in FY 2012. NICHD intends to commit $300,000 in FY 2012.

Award Budget

Application budgets are not limited, but need to reflect actual needs of the proposed project  A total budget of $1,800,000 is projected. Approximately $1,200,000 Direct Costs.

Award Project Period

 The maximum period  of funding is up to 5 years.  

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

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit 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 not allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least4-6 weeks prior to the application due date.

Eligible Individuals (Program Director(s)/Principal Investigator(s))

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 PD(s)/PI(s), visit the Multiple Program Director(s)/Principal Investigator(s) Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

It is anticipated that the PD(s)/PI(s) have requisite experience in the devleopment and implementation of a public web portal. The PD(s)/PI(s) should devote at least 3 calendar months to the Hub. Key personnel should have expertise in web programming, database design and management, and bioinformatics. Expert biological curation and annotation will also be required. NIDDK and NICHD would like to encourage all qualified applicants regardless of prior association with NURSA to apply to this FOA. The information systems, consulting, and database archiving tasks required to design and execute NURSA are highly technical, and require extensive experience, expertise, and long-term commitment. It is expected that applicants will have the technical capability and management skills to independently carry out this ambitious agenda.  PD(s)/PI(s) for NURSA Data Source Projects (NDSP) should be established, independently funded investigators. The projects should represent new directions or ideas. Instructions for application along with topic areas will be posted on the Hub web portal coincident with initiation of funding. NDSPs may request support for post-doctoral/graduate student effort, supplies and travel. No equipment may be requested. All NDSP recipients must agree to follow NURSA policies on data sharing.  

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.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

The letter of intent should be sent to:

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
Bethesda, Maryland 20817 (for courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the Appendix files must be sent to:

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
Bethesda, Maryland 20817 (for courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505

Page Limitations

All page limitations described in the PHS398 Application Guide and must be followed, with the following requirement:

Consortium Plan

Applicants should provide a plan for how the Hub will serve to integrate NDSPs, and other projects, to constitute the NURSA Consortium. Policy and procedures regarding consortia are defined by the NIH Grants Policy Statement ( Applicants should address this policy in defining how NURSA will constitute a consortium. The NURSA consortium will include investigators from the Hub, the NDSPs, and may also include collaborations with other NIH funded investigators. Since the NDSPs will be charged with advancing the scientific and technical agenda of NURSA funds should be set aside for as many as 6-8 such projects at up to $150,000 TC per year for 2-5 years beginning in the first year of funding. The Consortium Hub budget for Resources and the web portal will be limited to $600,000 TC for each of 5 years. The NDSPs will be funded as subcontracts from the Hub. Investigators may apply for only 1 NDSP at a time. NDSP investigators will be members of the SC for the period of time they are supported by NURSA, though affiliated membership may be offered subsequent to the end of the project period. The Hub should also budget accordingly for the annual investigator's retreat including EEC participation.

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies; GWAS) as provided in the PHS398 Application Guide, with the following modification:


Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide, with the following modification:

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates. 

Information on the process of receipt and determining if your application is considered “on-time” is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. 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.

6. Other Submission Requirements and Information

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

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

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115.

Section V. Application Review Information

1. Criteria

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

The NURSA Hub combines a discovery-based and hypothesis-generating/testing approach to data accrual and analysis together with a service role. The research role is therefore different from what might be expected in a standard R01 application and overall impact may involve consideration of the role that the Hub plays in integration of emerging and archived information and its presentation to the broader community. Although the NDSP program should be discussed, the topics for these projects will await consultation with leading experts in the field as well as with NIH staff.

Overall Impact - Overall

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

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


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


Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or 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(s)/PI(S), do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?  


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?   


Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? 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? 

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?   


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?       

Additional Review Criteria - Overall

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

Have the applicants provided a plan for solicitation and review of NDSPs and the integration of successful applicants into the NURSA consortium?      

Protections for Human Subjects

For research that involves human subjects but does not involve one of the six 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 six 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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.


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.


Not Applicable.


Not Applicable.


Not Applicable.

Additional Review Considerations - Overall

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

Applications from Foreign Organizations

Not Applicable.

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

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 NIDDK, in accordance with NIH peer review policy and procedures, using the stated review criteria. Review assignments will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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:

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

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 grantee’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 the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

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, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

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) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), 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 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 will be shared among the awardees and the NIH as defined below

Awardee Rights and Responsibilities

Awardees have primary responsibilities for the project as a whole, including research design, final data analysis and interpretation and preparation of publications, facilitating outreach to the broader nuclear receptor research community, and collaboration with other awardees (including those of the NDSPs); and affiliated members; with assistance from the NIDDK and NICHD Project Scientists. 

The tasks or activities in which awardees have primary substantial responsibilities include the further development of NURSA and the web portal (, management of the NURSA consortium, and scheduling of regular Steering Committee meetings, including agendas and logistics. 

Awardees retain custody and have primary rights to the data developed under these awards, subject to Government rights of access consistent with current HHS, PHS and NIH policies.  It will be the primary responsibility of the awardees to rapidly transfer data to the Hub upon verification of the data. 

Since the collection and storage of publicly available data is expected to be persistent beyond the project period for this announcement, the development and management of this data repository is a stewardship that shall be subject to transfer at the end of the project period.  Therefore, it is imperative that the database and core functions of the data repository be independent of physical location and that the software used is publicly available. 

The Hub must include technology transfer and sharing plans for both data and unique research resources that are generated by the projects in concordance with NIH policies on the sharing of data and resources.  The policies should be prominently displayed on the web portal.  Is is expected that resources developed by NURSA members will be made available to the broader scientific community, after a short propriety period, at no charge other than the cost of reproduction and distribution.  The grant application must also include a statement indicating the applicant’s willingness to abide by the Cooperative Agreement Terms and Conditions of the Award.  

NIH Staff Responsibilities:

The NIDDK Project Scientist will serve as the contact point for all facets of the scientific interaction with the awardee (s). As required for the coordination of activities and to expedite progress, NIDDK may designate additional NIDDK staff to provide advice to the awardee on specific scientific and/or analytic issues. Such staff may include another Project Scientist(s) or Analyst, who will provide direct technical assistance to the awardees to optimize the conduct and/or analysis of the study; or who may assist in the coordination of activities across multiple sites.

The NIDDK Project Scientist will participate in the Steering Committee that oversees consortium activities and represent the interests of other co-sponsoring NIH Institutes. The NIDDK Project Scientist or designee will be a full participant and voting member of the Steering Committee and, if applicable, subcommittees. NICHD may appoint an additional Project Scientist, and together with the NIDDK Project Scientist will serve as resources to NURSA investigators with respect to other ongoing NIH activities that may be relevant to NURSA activities.

The NIDDK and NICHD Project Scientists will have substantial involvement in assisting in the design and coordination of research activities for awardees as elaborated below:

The NIDDK and NICHD Project Scientists or designees may coordinate activities among awardees by assisting in the design, development, and coordination of a common research or clinical protocol and statistical evaluations of data; in the preparation of questionnaires and other data recording forms; and in the publication of results and in reviewing procedures for assessing data quality and study performance monitoring.

The NIDDK and NICHD Project Scientists or designees may be co-authors on study publications. In general, to warrant co-authorship, Project Scientists must have contributed to the following areas: (a) design of the concepts or experiments being tested; (b) performance of significant portions of the activity; (c) participate in analysis and interpretation of study results and (d) preparation and authorship of pertinent manuscripts.  

In addition, a separate NIDDK Program Official identified in the Notice of Award will be responsible for the normal stewardship and monitoring of the award including review and approval of all progress reports and all budgetary decisions.  Additional responsibilities include interacting with the principal investigator(s) on a regular basis to monitor study progress. Monitoring may include: regular communications with the principal investigator and staff, periodic site visits, observation of field data collection and management techniques, quality control, fiscal review, and other relevant matters; as well as attendance at Steering Committee and related meetings. The NIDDK Program Official will review and approve protocols prior to implementation to insure they are within the scope of peer review. The NIDDK will not permit further expenditures of NIDDK funds for a study after requesting closure except as specifically approved by the NIDDK. The NIDDK Program Official will make recommendations for continued funding based on: a) overall study progress, including sufficient patient and/or data accrual; b) cooperation in carrying out the research (e.g., attendance at Steering Committee meetings, implementation of group decisions, compliance with the terms of award and reporting requirements); and/or c) maintenance of a high quality of research, which will allow pooling of data and comparisons across multiple cooperative agreement awards for common data elements. 

NIDDK Program and Project Staff, as well as External Evaluation Committee (EEC) members will be responsible for generating the topics for NURSA Data Source Projects (NDSP) solicitations and for assuring appropriate peer review. NIH staff will employ external experts as part of this process through the External Evaluation Committee (EEC) which will assist in yearly assessment of progress in meeting milestones. The EEC will also assist with identification of topics for the NDSPs and in their review. The EEC will be advisory to both NIH staff and the NURSA Consortium. The NURSA EEC will meet annually to review interim progress and provide an annual report and recommendations to NIH and to the Steering Committee on NURSA activities.

Collaborative Responsibilities:   

After an award has been made the awardee will constitute an investigator's meeting at which a series of milestones will be developed along with timelines for their completion. A chair of the Steering Committee will be identified by NIH Staff in consultation with the awardees. In addition, an External Evaluation Committee will be constituted to meet periodically with the Awardees and NIH Staff to help evaluate progress against agreed upon milestones. The Principal Investigators of NURSA must indicate a commitment to be responsive to recommendations provided by the EEC. The NURSA Steering Committee will be responsible for organizing and providing minutes of these meetings. Members of the EEC will be nominated by the NURSA Steering Committee, selected and invited by the NIH. A chairman will be chosen from among the EEC membership, who will be accomplished senior scientists from academia and industry with backgrounds in the mission of NIDDK and the other co-sponsoring ICs, and technologies associated with web portal development and function, software use and development, and concepts of large scale data handling and analysis. If voting is necessary for an action item, members of the EEC and the EEC chair hold one vote each. The Steering Committee will discuss implementation of EEC recommendations, and provide a timeline and action plan for making changes. The action plan will be reported to the EEC.

At the outset at least two Steering Committee meetings will be held as in person meetings, jointly organized by the Awardees and the NIH staff. Other Steering Committee meetings will be held as teleconferences on a schedule defined by common agreement. The EEC will be in attendance at one such meeting. One of these meetings will be a broad investigator's retreat with all PIs and designees present at which scientific progress and opportunities will be presented and discussed. At other Steering Committee meetings. PIs will focus on strategic issues including development and review of annual milestones and timelines. The Steering Committee will be responsible for setting policy for the consortium, including final policies regarding access to the resources of the Hub. This will be done in consultation with NIH staff. The awardees in conjunction with NIH staff will also hold or participate in pertinent workshops designed to further the outreach and relevance of NURSA.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to arbitration. A dispute resolution panel will be composed of three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, 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 on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

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

Application Submission Contacts

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939

Scientific/Research Contact(s)

Corinne M. Silva, Ph.D.
Program Director
Intracellular and Intrauterine Signaling
Democracy 2, Room 794
6707 Democracy Blvd.
Bethesda, MD 20892-5460
Ph: 301-451-7335
Fax: 301-480-0475

Louis V. DePaolo, PhD
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Blvd, Room 8B01
Bethesda, MD 20892
Telephone: 301-435-6970

Peer Review Contact(s)

Dr. Francisco Calvo
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Room 752
Bethesda, MD 20892-5452
Bethesda, Maryland 20817 (for courier service)
Telephone: (301) 594-8897
FAX: (301) 480-3505

Financial/Grants Management Contact(s)

Todd Le
Senior Grants Management Specialist
National Institute of Diabetes and Digestive and Kidney Diseases(NIDDK)
Telephone: 301-594-7794

Ted Williams
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
6100 Executive Blvd, Room 8A17L
Bethesda, MD 20892
Telephone: 301-435-6996

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 Parts 74 and 92.

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