Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by a trans-NIH team led by the National Cancer Institute (NCI) (http:/www.nci.nih.gov) on behalf of the NIH Common Fund Program on Extracellular RNA Communication http://commonfund.nih.gov/extracellular_RNA/.
Funding Opportunity Title	Extracellular RNA Biogenesis, Biodistribution, Uptake, and Effector Function (U19)
Activity Code	U19 Research Project Cooperative Agreement
Announcement Type	New
Related Notices	None
Funding Opportunity Announcement (FOA) Number	RFA-RM-12-012
Companion Funding Opportunity	RFA-RM-12-014, (UH2/UH3) Phase Innovation Awards Cooperative Agreement RFA-RM-12-013, (UH2/UH3) Phase Innovation Awards Cooperative Agreement RFA-RM-12-011, (U01) Research Project Cooperative Agreement RFA-RM-12-010, (U54) Specialized Center--Cooperative Agreement
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
Funding Opportunity Purpose	The NIH invites applications for projects to determine the principles that guide the selection of regulatory RNA molecules for extracellular transport and to determine the function of these extracellular RNAs (exRNAs). The main scientific areas of interest include (1) exRNA biogenesis, (2) exRNA biodistribution, (3) uptake of exRNA by target cells, and (4) the physiological impact of delivered exRNA in target cells and tissues. Enabling tools, technologies, bioreagents, and innovative analytical approaches will likely be required to achieve the research goals. Therefore, awards funded under this FOA are anticipated to involve research conducted by multidisciplinary teams of investigators and focus on the role of exRNA communication in health and disease.

Posted Date	August 3, 2012
Letter of Intent Due Date	October 12, 2012
Application Due Date(s)	November 13, 2012
AIDS Application Due Date(s)	Not Applicable.
Scientific Merit Review	February - March, 2013
Advisory Council Review	May, 2013
Earliest Start Date(s)	July, 2013
Expiration Date	November 14, 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.

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

The concept that RNA molecules are secreted in the extracellular spaces and act as endocrine signals to alter the phenotypes of target cells, both locally and at distant sites, represents a novel paradigm in intercellular signaling.  Recent advances in RNA sequencing technologies have identified a large and diverse population of extracellular RNA (exRNA) including microRNA and long non-coding RNA (lncRNAs).  Given that approximately 60% - 80% of all protein encoding genes are regulated by microRNA and certain lncRNAs have been linked to regulation of the epigenome, extracellular delivery of these RNAs could have profound implications for a wide range of physiologic and pathologic processes. 

In humans, exRNAs are found in all body fluids examined, including blood, saliva, urine, breast milk, cerebral spinal fluid (CSF), amniotic fluid, ascites, and pleural effusions.  Recent reports in the literature suggest that exRNAs have both protective and pathogenic roles in a variety of human diseases.  Further, functional plant- and microbe-derived exRNAs have been identified in human serum and cells, suggesting that trans-kingdom exRNA communication could explain some associations between environmental exposures and health or disease. 

Taken together, the above findings highlight the transformative potential that secreted RNAs may have in the regulation of health and disease. However, to realize the potential that exRNAs may have as health/disease indicators and/or as therapeutic molecules, fundamental principles of their biogenesis, distribution, uptake, and function need to be defined. While exRNAs are known to be encapsulated in extracellular vesicles (EVs), recent studies have also demonstrated their presence in nuclease-resistant complexes with RNA-binding carrier proteins, such as HDL and Argonaut, in serum.  A better understanding of exRNA sorting to different secretory pathways, regulation of secretion, mechanisms of targeting, and effector function in target cells would generate opportunities to identify novel strategies for prognosis, diagnosis, and intervention of many diseases.   

The Common Fund Extracellular RNA Communication Program has been developed to address critical issues in this nascent field.  Both fundamental scientific discovery and innovative tools and technologies will be required to advance the field.  The key components (and associated FOAs) that need attention include: (a) defining the fundamental principles of exRNA biogenesis, distribution, uptake, and function and the development of the molecular tools, technologies, and imaging modalities to enable these studies (RFA-RM-12-012), (b) generating a reference catalog of exRNAs present in the body fluids of normal healthy individuals that would facilitate disease diagnosis and therapeutic outcomes (RFA-RM-12-011), (c) demonstrating the clinical utility of exRNAs as therapeutic agents and/or biomarkers and developing the scalable technologies required for these studies (RFA-RM-12-013 and RFA-RM-12-014); and (d) developing a community resource, the exRNA Atlas, to provide access to exRNA data, standardized exRNA protocols, and other useful tools and technologies generated by the exRNA consortium (RFA-RM-12-010).  Awards funded under these FOAs are anticipated to involve activities conducted by multidisciplinary teams of investigators.  Awardees from all 5 initiatives will form a consortium, with the overarching goal of determining fundamental principles associated with exRNAs. Comparisons across studies will be essential to establish these cross-cutting principles so investigators must be willing to act as part of the consortium. 

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

Purpose

This Funding Opportunity Announcement (FOA) seeks to stimulate innovative multi-component research projects to determine the regulatory principles that guide the selection of specific RNA and/or classes of RNA molecules for extracellular transport and the role of exRNA (including exRNAs from food and the environment) in human health and disease. Enabling tools, technologies, bioreagents, and innovative analytical approaches will likely be required to achieve the research goals. Thus, this FOA specifically solicits applications proposing collaborative and transdisciplinary research projects addressing four overarching scientific areas of interest including:

• exRNA Biogenesis: Elucidating the biosynthetic processes that sort RNAs destined for extracellular transport to specific secretory pathways,
• exRNA Biodistribution: Understanding how exRNAs travel through various body compartments,
• exRNA Uptake: Defining the mechanisms by which exRNA target specific tissues and/or cells and are taken up, and
• exRNA Effector Function: The impact of exRNA on target cell biology.

Applicants proposing multi-component U19 projects are strongly encouraged to consider the following key elements in writing their applications:

• Involve multi-disciplinary, collaborative teams of investigators.
• Propose transformative, high-impact studies connected by a unifying research theme that addresses the overarching goals of the FOA.
• Develop enabling tools, technologies, and bioreagents required to increase the knowledge of how RNAs are secreted and to track RNAs once secreted and/or taken up by recipient cells.

Specific Research Objectives

The four scientific areas of interest (exRNA biogenesis, biodistribution, uptake, and function) are further outlined below to highlight specific research areas where high quality multi-disciplinary research proposals could have a profound effect on the field.

exRNA Biogenesis:

Three principal regulatory RNA species, including protein encoding mRNA, long non-coding RNA, and microRNA have been identified in the extracellular space and reported to mediate intercellular communication. Both vesicles and RNA-binding carriers are reported to transport exRNA molecules in the extracellular space. Vesicle classes include endosomal-derived exosomes, membrane-derived microvesicles, and apoptotic bodies collectively referred to as extracellular vesicles. Non-vesicle, RNA-binding carriers include complexes containing lipoproteins (HDL) and RNA-binding proteins, Argonaut2 (AGO2) and Nucleophosmin 1 (NPM1). However, the subcellular processing pathways by which exRNAs are directed to specific secretory pathways and taken-up by specific target cells need to be elucidated. Examples of areas of emphasis include, but are not limited to, those listed below:

• Determine the biosynthetic pathways by which exRNAs are sorted to vesicles or RNA-binding carriers and secreted.
• Determine the molecular mechanisms that regulate secretion of exRNAs.
• Define inhibitors or proteins (that can be targeted) that control sorting and/or release of exRNA.

exRNA Biodistribution:

exRNAs are found at high concentrations in serum and other bodily fluids despite high extracellular RNase activity, indicating that exRNAs are protected from degradation. Mechanisms that regulate exRNA stability and distribution in the extracellular environment need to be identified. For example, whether exRNA from food or breast milk can survive the gastrointestinal tract and be taken up by the host needs to be clarified. Whether exRNA have limited/unlimited access to all bodily compartments or have targeted distribution patterns also needs to be elucidated. Examples of areas of emphasis include, but are not limited to, those listed below:

• Determine whether co-factors affect exRNA biodistribution.
• Generate novel systems and tools to track exRNA distribution in vivo.
• Assess stability and distribution of exRNAs from food and/or the environment.

exRNA Uptake:

Reports in the literature suggest that specific cell surface-targeting motifs on EVs mediate contact with target cells and mediate fusion events or uptake/endocytosis. Thus, receptor-ligand interactions may be involved. In the case of HDLs, the scavenger receptor class B, type I (SR-BI) binds HDL and mediates the uptake of cholesteryl ester from HDL. However, other mechanisms are likely to mediate uptake of different classes of exRNAs. Examples of areas of emphasis include, but are not limited to, those listed below:

• Determine how vesicles and RNA-binding proteins differ in their abilities to deliver exRNAs to target tissues or cells, both locally and systemically.
• Identify specific factors and their receptors on target cells which mediate binding and uptake.
• Determine how target cell uptake of vesicle or RNA-binding complexes is regulated and exRNA effector functions are enabled.
• Determine how exRNAs access specific subcellular compartments, such as the nucleus.

exRNA Effector Function:

exRNAs are thought to regulate target cell phenotype or function. Dynamic exRNA-mediated crosstalk between cells, both locally and systemically, are thought to be important in normal development and contribute to the onset, regulation, and resolution of various diseases. Examples of areas of emphasis include, but are not limited to, those listed below:

• Determine the functional outcomes on target cell phenotypes when exRNAs access the target cell.
• Identify and validate potential molecular targets for exRNA.
• Determine whether co-factors contribute to exRNA effector function in the target cell.

Applicants to this Funding Opportunity Announcement (FOA) are expected to propose multi-component, multi-disciplinary research projects focused on the functions of exRNAs and the mechanisms that regulate them. Research on model organisms may be required to establish fundamental principles governing exRNAs, but each U19 project should also include work in mammalian systems that validates results from less complex model systems. Validation in human samples is encouraged. Applicants are expected to have well thought-out plans and appropriate leadership structures for organizing and coordinating multiple component sub-projects, incorporating diverse, multidisciplinary approaches, recruiting and training personnel, and coordinating with other research projects funded by this FOA and other initiatives funded as part of the Common Fund Extracellular RNA Communication Program (see exRNA consortium agreement section below).

A key component of this program is the formation of consortium partnerships amongst all awardees. Each Notice of Grant Award will expect the execution of an Inter-Institutional Agreement by the grantee. A template for Inter-Institutional Agreements should serve as a guidance document to provide a framework under which consortium relationships are established. This and other templates, such as for Confidential Disclosure Agreements (CDAs) and Collaborative Research Agreements (CRAs), have been developed by the NIH Office of Technology Transfer). By participating in the consortium, the awardees agree to:

• Communication Plan
  • Participate in regular (monthly) conference calls with all consortium members
  • Coordinate efforts with other awardees, in particular with the DMRR
  • Participate and present findings at annual workshops convened by the NIH through the DMRR
  • Jointly publish findings in a timely manner
• Performance Requirements
  • Meet yearly milestones as defined by investigators and NIH program at the time of award
  • Work with, cooperatively interact with, and actively seek input from NIH,
• Sharing Plan
  • Broad sharing of data and biological specimens with academic, industry and government researchers is a critical feature of this program that is consistent with applicable laws, regulations, and policies. All subjects must be properly consented to allow appropriate sample and data distribution to researchers in academics and industry.
  • The DMRR and designated NIH databases will be utilized for the banking and distribution of biological and clinical data. Project PD(s)/PI(s) will be expected to harmonize all data and resource generation with the Data Management and Resource Repository (DMRR). The DMRR is expected to curate and disseminate information regarding critical reagents, and resources as well as promote and facilitate cross-project collaborations (see RFA- RM-12-010).

Funding Instrument	Cooperative Agreement
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The total amount of funds available is $ 7.2 million total costs per year. It is anticipated that 4-6 projects will be supported.
Award Budget	Application budgets are not limited, but need to reflect actual needs of the proposed project.
Award Project Period	Scope of the proposed project should determine the project period. The maximum period is 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.

Higher Education Institutions

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

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

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

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, including the NIH intramural research 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 eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

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.

• Central Contractor Registration (CCR) must maintain an active registration, to be renewed at least annually
• eRA Commons

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.

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.

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

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.

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

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.

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 research.
• Name, address, and telephone number of the PD(s)/PI(s).
• Names of other key personnel.
• Participating institutions.
• Number and title of this funding opportunity.

The letter of intent should be sent to:

T. Kevin Howcroft, Ph.D. (on behalf of the NIH Common Fund Extracellular RNA Working Group) 
Program Director
Cancer Immunology and Hematology Branch
Division of Cancer Biology
National Cancer Institute (NCI)
6130 Executive Boulevard
EPN Room 5060 MSC 7388
Bethesda, MD 20892-7388 (for U.S. Postal service express or regular delivery)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-7815
Email: [email protected]

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:

Referral Officer
National Cancer Institute
Division of Extramural Activities
6116 Executive Boulevard, Room 8041, MSC 8329
Bethesda, MD 20892-8329 (for U.S. Postal service Express or regular mail)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: (301) 496-3428
FAX:  (301) 402-0275
Email: [email protected]

All page limitations described in the PHS398 Application Guide and the Table of Page Limits must be followed.

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

The following section supplements the instructions found in Form PHS 398 for preparing a multi-component project application. Additional instructions are required because the Form PHS 398 is designed primarily for individual, free-standing research project grant applications, and has no specific instructions for multi-component projects consisting of component sub-projects interrelated by a common theme.  The supplemental instructions are divided as follows:

This section addresses the overall project application and the collaborative efforts among individual component sub-projects and core facilities; the administrative and organizational structure; the overall facilities and environment; and the overall budget. It is expected that multi-component project applications will have 2-4 component sub-projects and 1-2 core facilities.

This section describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of each individual research component sub-project of the overall project.

This section describes modifications to PHS Form 398 instructions on selected items to address the collaborative or interactive role of shared core facilities with each individual research component sub-project and with the overall project.

All applications must be submitted on Form PHS 398. The multi-component project application should be assembled and paginated as one complete document.

1. Face Page:

(PHS 398 Form Page 1; Instructions for PHS 398, Part 1.Section 4.1).

Items 1 - 14: complete these items as instructed. This should be the first page of the entire application and all succeeding pages should be numbered consecutively.

If multiple PD(s)/PI(s) are proposed, use the Face Page-Continued page to provide Items 3a 3h for all PD(s)/PI(s). NIH requires one PD/PI be designated as the contact PD/PI for all communications between the PD(s)/PI(s) and the agency. The contact PD/PI should be listed in

block 3 of Form Page 1 (the Face Page), with all additional PD(s)/PI(s) listed on Form Page 1-

Continued. When inserting the name of the PD/PI in the header of each application page, use

the name of the Contact PD/PI, et.al. The contact PD/PI must be from the applicant

organization if the PD(s)/PI(s) are from more than one institution.

2. Description (PHS 398 Form Page 2):

(PHS 398 Form Pages 2 and Form Page 2-continued; Instructions for PHS 398, Part 1. Section 4.2).

Description: Overall Project Summary and Relevance

The Project Summary/Description serves as a succinct and accurate description of the overall

multi-component project. State the project’s broad, long-term objectives and specific aims. State the contribution of each component sub-project and shared resource core to the overall theme and goals of the project. The second element of the Description is Relevance. Using no more than two or three sentences, describe the relevance of the work proposed in the overall project to public health. Use plain language that can be understood by a general, lay audience.

Project/Performance Sites

List the performance sites where the research will be conducted.

Key Personnel

Under "Key Personnel", list the PD(s)/PI(s) of the overall project application, followed by the Project Leaders of the component sub-projects, other key personnel, and other significant contributors.

3. Table of Contents (PHS 398 Form Page 3):

(PHS 398 Form Page 3; Instructions for PHS 398, Part 1. Section 4.3).

A more comprehensive table of contents is needed for a multi-component application. Modify the standard PHS 398 Table of Contents to account for the modified sections of the Research Plan (see below) to account for a multi-component application.

Bearing in mind that the application will be reviewed scientifically component by component, prepare a detailed Table of Contents that will enable reviewers to readily locate specific information pertinent to the overall project as well as to each component sub-project in the application. A page reference should be included for the budget for each component sub-project. Further, each component sub-project should be identified by number (e.g. Sub-Project 1), title, and responsible Project Leader. The page location of a COMPOSITE BUDGET should be indicated in the "Table of Contents."

4. Budget (PHS 398 Form Pages 4 and 5):

(PHS 398 Form Page 4; Instructions for PHS 398, Part 1. Section 4.4 - 4.5).

Follow the current PHS 398 instructions to provide a detailed budget (direct costs) for the entire application for the first 12-month period (Form page 4) and the entire proposed project period (Form page 5).

Use additional Form Pages 4 and 5 to provide separate budget information for each component sub-project (first year and cumulative budgets for the entire project period).

6. Biographical Sketch

(Instructions for PHS 398, Part 1. Section 4.6).

Place all the Biographical Sketches together in one section following the overall budget for the project. Place the biographical sketch of the PD/PI first, followed by the biographical sketches of all other personnel in alphabetical order. It is helpful if each person is identified by listing the component sub-project or shared support core in the upper left corner of the biographical sketch. If Multiple-PD(s)/PI(s) are proposed, place the Biographical Sketch of the Contact PD/PI first, followed by the biographical sketches of the other PD(s)/PI(s) in alphabetical order, followed by the biographical sketches of all other personnel in alphabetical order.

7. Resources

Do not complete.  Essential information is to be presented in the individual research component and core sections of the application.

8. Multi-Component Project Overview (Research Objectives and Strategic Plan)

This narrative section summarizes the overall research plan for the multi-component project and is limited to twelve (12) pages and should contain the following sections:

Specific Aims

List the broad, long-range objectives and goals of the proposed multi-component project. Concisely and realistically describe the hypothesis or hypotheses to be tested.

Overall Research Strategy

The multi-component project should be viewed as a confederation of interrelated research sub-projects, each capable of standing on its own scientific merit, but complementary to one another. This is an important section for it provides the group of investigators an opportunity to give conceptual wholeness to the overall project by defining the major research questions and opportunities and laying out a broad strategy for attacking the problems. As the strategy develops, each component sub-project should be cited briefly as to its place in the overall scheme. Summarize the special features in the environment and/or resources that make this application strong or unique. In particular, highlight, (1) the multidisciplinay approaches and innovative capabilities of the research team, (2) what new research directions are likely to emerge from the proposed studies, and (3) general plans to ensure flexibility in redirecting research when scientific progress in the field warrants it. The Research Strategy section should also include overall milestones, timeline, and future plans.

Milestones and Timelines

A timeline (Gantt chart) including milestones is expected for all studies. Yearly quantitative milestones are expected in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline for each stage must be provided in a separate heading at the end of the Approach section.

• Provide detailed quantitative criteria by which milestone achievement will be assessed.
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
• Identify any impediments to the research plan, milestones, or timeline with a discussion of alternative approaches.

Leadership and Applicant Group

Use this portion to summarize the expertise and experience of the leadership and key investigators of the multi-component research team that are relevant to the proposed research theme and specific components. Specify the anticipated collaborative interactions of the investigators in the group. Outline the leadership structure of the proposed program and the roles of key personnel, collaborators, and consultants who are associated with the application.

Provide a detailed plan that includes a discussion of the administrative structure and roles of administrative staff, including the training and experience of proposed staff and the functions to be performed; how fiscal and other resources will be prioritized, allocated and managed; how communications will be facilitated; and how research related travel and training will be budgeted. Funding for the overall administrative efforts, including administrative services, expenses for publications demonstrating collaborative efforts, communication expenses, and travel should be requested in the PD(s)/PI(s) project. Note that applicants should include in their budgets sufficient travel-related funds to attend bi-annual workshops to be held in conjunction with investigators funded under this Common Fund initiative on Extracellular RNA Communication. The yearly budget for the bi-annual workshops to be held in the greater Washington, D.C. metro area is not to exceed $6,000.

9. Checklist

(PHS 398 Checklist Form Page; Instructions for PHS 398, Part 1. Section 5.6).

One checklist, placed at the end of the application, is to be submitted for the entire application.

10. Appendix Materials

(Instructions for PHS 398, Part 1. Section 5.7).

Except for the requirements below, follow the PHS 398 Specific Instructions found at http://grants1.nih.gov/grants/funding/phs398/phs398.doc#_Toc130797900 in preparing each research component sub-project.

For each individual Research Component Sub-Project, include:

• Face page (see special instructions, below)
• Description & Key personnel (PHS 398 Form Page 2)
• Table of Contents (PHS 398 Form Page 3)
• Budget Pages (PHS 398 Form Pages 4 and 5); with budget justifications
• Research Plan
• Resources

1. Cover Page

The Face Page of the 398 Form should not be used as a cover page for the individual research component sub-projects.  Instead, use the PHS 398 continuation page to create a "Cover Page" containing selected data about each individual research component sub-project.  This Cover Page will demarcate each individual research component sub-project and should contain the following information items (these are a subset of the information provided on a PHS 398 Face Page):

• Project Number and Title
• Name of Sub-Project Leader
• Human Subjects
• If Yes
  • Exemption number, -or-
• IRB Approval Date and Federalwide Assurance (FWA) number
• Vertebrate Animals
• If Yes
  • IACUC Approval Date and Animal welfare assurance number:
• Proposed Period of Support
  • From: (mmddyyyy)
  • To: (mmddyyyy)
• Costs Requested for Initial Budget Period
  • Direct Costs
  • Total Costs
  • Costs Requested for the Entire Budget Period
• Applicant Organization (full address)

2. Description

Description: Project Summary and Relevance

Provide a description (abstract) of the research proposed in the research component sub-project according to the instructions on Form Page 2 of PHS Form 398. In addition, the abstract should contain a brief description of how the individual research component sub-project will contribute towards attainment of the overall project objectives. The second element of the Description is Relevance. Using no more than two or three sentences, describe the relevance of the work proposed in the individual component sub-project to public health. Use plain language that can be understood by a general, lay audience.

Project/Performance Sites

List the performance sites where the research will be conducted.

Key Personnel

Under "Key Personnel", list the Sub-Project Leader, followed by other key component personnel, and then other significant contributors.

3. Table of Contents

Prepare a Table of Contents for the component sub-project using Form Page 3 of the PHS 398.

4. Detailed Budget for Initial Budget Period

Prepare a detailed budget and justification for the component sub-project using Form Pages 4 and 5 of the PHS 398. Note that applicants should include in their budgets sufficient travel-related funds to attend bi-annual workshops to be held in conjunction with investigators funded under this Common Fund initiative on Extracellular RNA. The yearly budget for the bi-annual workshops to be held in the greater Washington, D.C. metro area is not to exceed $6,000.

5. Individual Research Component Sub-Project Research Plan

Specific Aims (Limited to 1 page.)

Organize the Specific Aims in the specified order as stated in the PHS 398 Instructions, Section 5.5.2. List the broad long-range objectives and goals of the application. Concisely and realistically describe the hypothesis or hypotheses to be tested. In addition, state the component sub-project's relationship to the overall project goals and how it relates to other components.

Research Strategy (Limited to 12 pages.)

Use this section to describe how the proposed research will contribute to meeting the goals and objectives and explain the rationale for selecting the methods to accomplish the specific aims. In addition to stating the biological significance of the research, indicate the component sub-project's relevance to the primary theme of the application.

Organize the Research Strategy in the specified order as stated in the PHS 398 Instructions, Section 5.5.3. Make sure to start each section with the appropriate section heading in order, Significance, Innovation, Approach, and include the appropriate information. Experimental details should be cited using the Bibliography and Reference Cited section and need not be detailed in the Research Strategy. Preliminary Studies to support the research aims must be included as part of the approach section, and must be contained within the page limits of the Research Strategy section. The Research Strategy section should also include overall milestones, timeline, and future plans.

Milestones and Timelines

A timeline (Gantt chart) including milestones is expected for all studies. Yearly quantitative milestones are expected in order to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Milestones and the timeline for each stage must be provided in a separate heading at the end of the Approach section.

• Provide detailed quantitative criteria by which milestone achievement will be assessed.
• Provide a detailed timeline for the anticipated attainment of each milestone and the overall goal.
• Identify any impediments to the research plan, milestones, or timeline with a discussion of alternative approaches.

6. Resources

Organize the Resource section as stated in the PHS 398 Instructions, Section 4.7. Provide information on resources available for the component sub-project. Describe how the scientific environment in which the research will be done contributes to the probability of success (e.g., institutional support, physical resources, and intellectual rapport.) For Early Stage Investigators, describe institutional investment in the success of the investigator. If there are multiple performance sites, describe the resources available at each site. Describe any special facilities used for working with biohazards or other potentially dangerous substances.

7. Biographical Sketch

Do not repeat the biographical sketches of participating investigators since this information will be included in the overall project application (and therefore will be referenced in the Overall Table of Contents).

A multi-component project application may include shared resource cores that provide administrative,

laboratory facilities, equipment, and/or services to be shared by two or more component sub-projects. A core is a shared central laboratory, research facility, service, or resource whose function is essential to the scientific purpose of the overall project. Each core is directed by an investigator with substantial expertise related to the core. Facilities may be proposed that will enhance productivity or in other ways benefit a group of investigators to accomplish stated goals. 

For each shared resource core component, follow instructions for the Individual Research Component, as described above and in the Instructions to the PHS 398, Part 1, Sections 4.2 through 5.5. The general format for a shared resource core follows that of a component sub-project except for the Research Plan.

1. Title Page

Do not use the PHS 398 Face Page for shared resource cores. Use PHS 398 Continuation Pages. Clearly denote the shared resource core letter, the title of the core, and the core director’s name and professional degrees.

2. Description/List of Key Personnel (PHS 398 Form Page 2a and b).

Provide a summary of the services, facilities, equipment, etc., that the shared resource core will provide, and which component sub-projects of the overall program the shared resource core will serve.

3. Omit the PHS 398 Table of Contents form.

4. Detailed Budget and Budget for Entire Proposed Period of Support (PHS 398 Form Pages 4 and 5) Follow instructions in the PHS 398 form (Part 1, Section 4), and the instructions for component budgets above.

5. Biographical Sketch (Do not include Biographical Sketches in the shared resource cores, since they are grouped following the Overall Budget.

6. Resources (PHS 398 Resources Format Page) Follow the instructions on the PHS 398 Resources Format Page. List only those resources specific to the shared resource core.

7. Shared Resource Core Services Plan. Do not exceed the specified page limits. All tables, graphs, figures, diagrams, and charts must be included within the page limit.

• Specific Aims (Do not exceed one page.)
• Core Services Strategy (Do not exceed 6 pages for the Core Services Strategy). Clearly describe the facilities, equipment, methods, services, etc., that will be provided by the shared resource core and how they meet the needs of two or more of the proposed research component sub-projects and how provision of the proposed services will facilitate accomplishment of the proposed goals and objectives of the overall project as a whole. Provide the rationale for centralizing the proposed services in the core, rather than including them in individual component sub-projects. Address plans for prioritization of services (if necessary).
• Include Items in the PHS 398 instructions Part 1 Section 5 as appropriate. The multiple PI option is not available for individual shared resource cores.

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.

Appendix

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.

Foreign (non-US) Institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the PHS398 Application Guide.

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.

This initiative is not subject to intergovernmental review.

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.

Applicants should include in their budgets sufficient travel-related funds to attend bi-annual workshops to be held in conjunction with investigators funded under this Common Fund initiative on Extracellular RNA. The yearly budget for the bi-annual workshops to be held in the greater Washington, D.C. metro area is not to exceed $6,000.

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.

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

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

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

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.

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).

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

Significance

Does the project address an important problem or a critical barrier to progress in the field? 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?

In addition, specific to this FOA:

If the aims of the application are achieved, will the findings significantly increase our understanding of the biosynthetic pathways by which RNAs are directed for extracellular transport and of the mechanisms that regulate their secretion, biodistribution, uptake, and of their biological functions?

Are the exRNAs to be studied (if model systems are utilized) likely to be relevant to human biology?

Investigator(s)

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?

In addition, specific to this FOA:

How appropriate are the expertise and experience of the PD/PI(s) in the context of exRNA?

Does the investigative team bring complementary multidisciplinary scientific expertise required for integrated and comprehensive approaches to key research problems proposed?

A key NIH Common Fund requirement is the formation of a highly collaborative network consisting of all Extracellular RNA Communication Program awardees. Considering this critical element, do the project PD(s)/PI(s) have the necessary skills and experience to contribute to the success of this consortium?

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?

In addition, specific to this FOA:

Will the complementary perspectives of the research team enable innovative approaches that would not be likely without a coordinated team effort?

Approach

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?

In addition, specific to this FOA:

• Are the component sub-projects sufficiently trans-disciplinary and scientifically well integrated?
• Are the plans sufficiently flexible to exploit emerging research opportunities?
• Are appropriate and quantifiable milestones and timelines clearly defined?

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?

As applicable for the overall 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.

Review Criteria for Individual Research Projects:

Significance: Does the component sub-project address an important problem or a critical barrier to progress in the field? If the aims of the sub-project are achieved, will scientific knowledge and technical capabilities be greatly enhanced? Will the knowledge gained provide significant insights into human health and disease? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

In addition, specific to this FOA:

If the aims of the application are achieved, will the findings significantly increase our understanding of the biosynthetic pathways by which RNAs are directed for extracellular transport and of the mechanisms that regulate their secretion, biodistribution, uptake, and of their biological functions?

Investigator(s): Are the sub-project Leaders, 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?

Innovation: Does the sub-project challenge and seek to shift current research 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?

Approach: Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the sub-project? Are potential problems, alternative strategies, and benchmarks for success presented? If the sub-project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Is the approach well aligned with the overall goals for the project?

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 proposed work? Will the sub-project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Review Criteria for Cores:

Significance

Does the Core meet the needs of the overall project?  If the aims of the Core are achieved, will concepts, methods, or technologies result that may advance exRNA research?  Is the Core well integrated with the other component sub-projects? 

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the overall project?  Do they have appropriate experience and training to accomplish the aims of the Core?  Have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the Core is collaborative or multi-PD(s)/PI(s), do the investigators have complementary and integrated expertise; are their leadership approaches, governance and organizational structure appropriate for the project?  

Approach

Are milestones adequately developed and quantitative, to serve as effective guidance for assessment of progress? Are key scientific or technological challenges addressed early in the project?  

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?

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.

Biohazards

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

Resubmissions

Not Applicable.

Renewals

Not Applicable.

Revisions

Not Applicable

As applicable for the proposed project, 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

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) 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.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review,, 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:

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/priority 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 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:

• 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.

After the peer review of the application is completed, the PD(s)/PI(s) 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.

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.

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.

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS 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 may be shared among the awardees and the NIH as defined below.

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

• Determining experimental approaches, designing protocols, setting project milestones and conducting experiments;
• Adhere to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity;
• Submit biannual progress reports in a format as agreed upon by the NIH Common Fund Extracellular RNA Steering Committee;
• Accept and implement any other common guidelines and procedures developed for the NIH Common Fund Extracellular RNA Program and approved by the NIH Common Fund Extracellular RNA Steering Committee;
• Accept and participate in the cooperative nature of the NIH Common Fund Extracellular RNA Consortium;
• Attend bi-annual workshops organized by the NIH and the DMRR.

Intellectual Property

The NIH recognizes that intellectual property rights may play a role in achieving the goals of this program. To this end, all awardees shall understand and acknowledge the following:

• The awardee is solely responsible for the timely acquisition of all appropriate proprietary rights, including intellectual property rights, and all materials needed for the applicant to perform the project.
• Before, during, and subsequent to the award, the U.S. Government is not required to obtain for the awardee any proprietary rights, including intellectual property rights, or any materials needed by the awardee to perform the project.
• The awardee is required to report to the U.S. Government all inventions made in the performance of the project, as specified by 35 U.S.C. Sect. 202 (Bayh-Dole Act).

Awardees are expected to make new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH Common Fund Extracellular RNA Steering Committee, and other mechanisms.

Data

Awardees will retain custody of and have primary rights to the data and resources developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

Publications

The Program Director(s)/Principal Investigator(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The Program Director(s)/Principal Investigator(s) and Project Leaders are requested to submit manuscripts to the NIH Project Scientist within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the Program Director(s)/Principal Investigator(s) and appropriate Project Leaders and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.

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

NIH Common Fund Extracellular RNA Communication Project Scientists will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of NIH Common Fund Extracellular RNA Project Scientists will be to facilitate and not to direct the activities.

Each NIH Common Fund Extracellular RNA Project Scientist shall participate as a member of the NIH Common Fund Extracellular RNA Steering Committee

The Project Scientists will:

• Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted. The Project Scientists will assist and facilitate the group process and not direct it;
• Serve as a liaison between the awardees, the Advisory Councils for those Institutes that plan to administer elements of the NIH Common Fund Extracellular RNA Program and the larger scientific community;
• Coordinate the efforts of the awardee with others engaged in exRNA research, including other awardees under this FOA and those awardees involved in related NIH programs;
• Attend all Steering Committee meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Periodically report progress to the Directors, NIH institutes involved in the NIH Common Fund Extracellular RNA Initiative and the Directors of the Division of Program Coordination, Planning, and Strategic Initiatives and Office of Strategic Coordination;
• Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve as External Scientific Consultants.
• Serve as liaison between the Steering Committee and the External Scientific Consultants;
• Serve on subcommittees of the Steering Committee as appropriate;
• Provide advice in the management and technical performance of the investigation;
• Assist in promoting the availability of data and resources developed in the course of this project to the scientific community at large;
• Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through this initiative
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend the withholding or reduction of support from any cooperative agreement that either substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

A Steering Committee will serve as the main governing board of the Extracellular RNA

Communications Network.  The Steering Committee membership will include NIH Project Scientists and the PI of each awarded cooperative agreement. The PI of each award (or designee) will have one vote on the Steering Committee. The Project Scientists may vote, but the total votes will count as a maximum of one-third of the total number of votes.  The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. The Steering Committee will:

• Discuss progress in meeting the goals of various exRNA projects;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for data quality measures and assessment, conventions for data deposition, or measuring costs and throughput.
• The Steering Committee will also serve as a venue for coordination on the improvement of exRNA scientific methods, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies.
• The Steering Committee will consider collective goals for the Consortium, will determine how joint publication of results will contribute toward the goals of the exRNA Program, and will coordinate joint publication as needed to demonstrate overarching principles of exRNAs. It will schedule the time for, and prepare concise (3 to 4 pages) summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting.
• Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

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 Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have 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.

External Scientic Consultants:

The External Scientific Consultants (ESC) will be responsible for reviewing and evaluating the progress of the exRNA Communications Network toward meeting their individual and collective goals. The ESC will be appointed by and provide recommendations to the NIH about continued support of the components of the Network. The Consultant Panel is composed of four to six senior scientists with relevant expertise who are not PIs of a cooperative agreement involved in the Network. The membership of the ESC may be enlarged permanently, or on an ad hoc basis, as needed. 

The ESC will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESC to interact directly with the awardees. Annually, the ESC will provide comments regarding progress of the Consortium and on any changes that may be necessary to the NIH.

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 www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: [email protected]

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
Email: [email protected]

T. Kevin Howcroft, Ph.D. (on behalf of the NIH Common Fund Extracellular RNA Working Group) 
Program Director
Cancer Immunology and Hematology Branch
Division of Cancer Biology
National Cancer Institute (NCI)
6130 Executive Boulevard
EPN Room 5060 MSC 7388
Bethesda, MD 20892-7388 (for U.S. Postal service express or regular delivery)
Rockville, MD 20852 (for non-USPS delivery)
Telephone: 301 496-7815
Email: [email protected]

Richard Panniers, Ph.D.
Chief
Genes, Genomes and Genetics
Center for Scientific Review (CSR)
Telephone: 301 435-1741
Email: [email protected]

Crystal Wolfrey
Deputy Director
Office of Grants Administration
National Cancer Institute
Phone: 301 496-8634
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Parts 74 and 92.