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 Office of Strategic Coordination, Division of Program Coordination, Planning, and Strategic Initiatives, Office of the NIH Director (http://dpcpsi.nih.gov/osc/). This FOA will be administered by the National Institute of Mental Health (NIMH) on behalf of the NIH.
Funding Opportunity Title	Exceptionally Innovative Tools and Technologies for Single Cell Analysis (R21)
Activity Code	R21 Exploratory/Developmental Research Grant Award
Announcement Type	New
Related Notices	December 19, 2013 - This RFA has been reissued as RFA-RM-13-021.
Funding Opportunity Announcement (FOA) Number	RFA-RM-11-014
Companion FOA	U01 RFA-RM-11-013; R01 RFA-RM-11-015
Number of Applications	See Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestic Assistance (CFDA) Number(s)	93.310
FOA Purpose	This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health, solicits early stage, high-risk/high-impact applications to develop next-generation tools that distinguish heterogeneous states among cells in situ. Applications should define the current state of technology as a benchmark against which the new tool(s) will be measured and should propose proof-of-concept testing of the tool(s) in a complex biological tissue or living organism. The new tools should provide substantially increased sensitivity, selectivity, spatiotemporal resolution, scalability or non-destructive analysis of multiple global or functional measures of single cells. These novel technologies will aid in obtaining a fine-grained, integrative and dynamic view of heterogeneous cellular states/classes and will provide innovative platforms to transform research into the cellular basis of diseases.

Posted Date	November 23, 2011
Open Date (Earliest Submission Date)	December 23, 2011
Letter of Intent Due Date	December 23, 2011
Application Due Date(s)	January 23, 2012, by 5:00 PM local time of applicant organization.
AIDS Application Due Date(s)	Not applicable
Scientific Merit Review	March, 2012
Advisory Council Review	August, 2012
Earliest Start Date(s)	September, 2012
Expiration Date	January 24, 2012
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the SF 424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

This Funding Opportunity Announcement (FOA) issued by the National Institutes of Health, solicits early stage, high-risk/high-impact applications to develop next-generation tools that distinguish heterogeneous states among cells in situ. Applications should define the current state of technology as a benchmark against which the new tool(s) will be measured and should propose proof-of-concept testing of the tool(s) in a complex biological tissue or living organism. The new tools should provide substantially increased sensitivity, selectivity, spatiotemporal resolution, scalability or non-destructive analysis of multiple global or functional measures of single cells. These novel technologies will aid in obtaining a fine-grained, integrative and dynamic view of heterogeneous cellular states/classes and will provide innovative platforms to transform research into the cellular basis of diseases.

This initiative is part of the Single Cell Analysis Program (SCAP) and is funded through the NIH Common Fund (See http://nihroadmap.nih.gov/), which supports cross-cutting programs that are expected to have exceptionally high impact. Common Fund initiatives address key roadblocks in biomedical research that impede basic scientific discovery and its translation into improved human health. In addition, these programs capitalize on emerging opportunities to catalyze progress across multiple biomedical fields.

Single cell analysis has recently emerged as an important field of research because technologies have improved in sensitivity and throughput sufficiently to begin measuring and understanding heterogeneity in complex biological systems and correlating it with changes in biological function and disease processes. By profiling individual cells it is possible to resolve rare cells, transient cell states, and the influence of organization and environment on such cells and states, which cannot be described by ensemble measurements. The long-term goal of the SCAP is to accelerate this move towards personalizing health to the cellular level by understanding the link between cell heterogeneity, tissue function and emergence of disease through the discovery, development and translation of innovative approaches which will dramatically change the way cells are characterized.

The SCAP will focus on supporting work which will systematically measure, analyze and model cell-to-cell variation, and identify crucial differences and rare biological states, which may have important functional consequences. To robustly and systematically describe cell level heterogeneity, projects are expected to take a multiplexed approach with minimal perturbation, which can be applied reproducibly to any complex tissue. Technologies and methods must also be capable of capturing spatiotemporal information to understand the organization, evolution and response of cell states as part of a functional population. In addition, the SCAP emphasizes the application of these technologies to in situ populations of cells from multicellular organisms to link cell state measurements with complex, functional tissues which can inform our understanding of disease processes.

The SCAP has been designed as a five-year program with several components: (1) the collection, analysis and sharing of comprehensive expression datasets to understand the role of heterogeneity in tissues and systemically and to identify critical parameters and states; (2) the discovery of new, innovative tools for spatiotemporal imaging, manipulation, analysis and modeling of a biologically relevant population of cells with minimal perturbation; (3) milestone-driven validation and translation of technologies for characterizing single cells in situ meeting the needs of end-users; and (4) development and coordination of a multidisciplinary research community through workshops and other collective endeavors. Further details can be found on the Program s website (http://commonfund.nih.gov/singlecell/).

This FOA solicits applications to develop next-generation, innovative technologies to better define cell heterogeneity in situ. These techniques should provide new analytical measures and manipulations of cellular contents, structure and activity significantly beyond those currently available at the single cell level. Of particular interest are first-in-class and/or cross-cutting techniques. The goal of this FOA is to accelerate early stage development of promising concepts by focusing on overcoming technical challenges, building prototype systems and testing performance on a population of cells in situ (e.g., explant, whole organism).

Applications should propose early-stage, high-risk/high-impact technologies; examples can include but are not limited to:

• Devices to perform novel global (i.e., "-omic") and/or functional analyses of a wide variety of cell types in situ without destruction or prior perturbation of cells.
• Combinations of tools for multiplex analysis and/or manipulation of single cells in situ to maximize data content over many parameters (e.g., gene expression, electrochemical dynamics, signal secretion/reception/transduction, cell adhesive properties, cytoarchitectonic or migratory changes).
• Tools that provide significant advances in sensitivity, selectivity or spatiotemporal resolution of molecules/structures/activities within single cells and between ostensibly similar cells in situ.
• Automated and scalable assays for high-throughput analysis of single cells in situ, including scalability of measured parameters in parallel, cell numbers and/or speed of processing.
• Systems-level single cell dataset analysis or modeling, including computational approaches, in the context of tissues or whole organisms.

Research designs should focus on tool development, but tools may be tested in the context of heterogeneous biological systems, such as: identifying spatiotemporal transitions in cellular states (e.g., progenitor lineage determination, cellular aging); detection of rare cells in a population (e.g., stem cells, tumor-initiating or metastatic cells, drug resistant cells); elucidating the molecular signatures or functional consequences of stochastic variation in cellular states (e.g., genomic stability, clonal selection and evolution, asymmetric division, cell specification); or characterizing heterogeneous cell responses to environmental changes (e.g. homeostatic perturbation, modulation of niche/microenvironment, morphogens or cell-to-cell signaling, toxicological exposure, experience-dependent plasticity, host cell responses to infectious, immunological or allergic challenges). Applicants are expected to explain the significance of the specific technical approach with respect to characterizing cell heterogeneity in situ. However, any proposed biological assay(s) should be chosen strictly for utility (rather than biological novelty) in proof-of-concept testing of the innovative technique.

NIH understands and accepts that early stage, high-risk/high-impact applications that are responsive to this solicitation will be much riskier than for most other solicitations. Applications will be considered based on the expected technological impact relative to risk. All applications must explicitly address considerations detailed in Section IV below (Application and Submission Information).

Funding Instrument	Grant
Application Types Allowed	New The OER Glossary and the SF 424 (R&R) Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	The number of awards is contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications. NIH intends to fund an estimate of 8-12 awards, corresponding to a total of $4,000,000, for fiscal year 2012. Future year amounts will depend on annual appropriations..
Award Budget	Direct costs are limited to $275,000 over a 2-year project period, with no more than $200,000 in direct costs allowed in any single year.
Award Project Period	The maximum project period is 2 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 - NIH Intramural Program
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

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 SF 424 (R&R) 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
• Grants.gov
• eRA Commons

All Program Directors/Principal Investigators (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 least 4-6 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 SF 424 (R&R) 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. NIH will not accept any application that is essentially the same as one already reviewed.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) 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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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. Applicants are encouraged to submit a letter of intent in order to get feedback on responsiveness prior to preparing a full application.

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

• Descriptive title and outline 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:

David M. Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7186, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-5288
FAX: (301) 451-5615
Email: [email protected]

The forms package associated with this FOA includes all applicable components, mandatory and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate optional components.

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

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

Research Strategy

All applications should include the following: (1) Investigators should specifically define the current state of technology as a benchmark against which their proposed technology will be measured. (2) At least one proof-of-concept test, involving analysis of individual cells among a heterogeneous population using an in situ (e.g., explant, whole organism) biological system, should be proposed during the project period. (3) There should be a particular focus throughout the application on risk management, including alternative strategies if the original plan fails to reach expected performance. (4) Applicant should budget for attendance at the annual SCAP workshop, which will be used to build synergy between the supported grants.

Applicants are expected to explain the significance of the specific technical approach with respect to characterizing cell heterogeneity in situ. However, research designs should focus on innovative tool development for in situ analysis of single cell heterogeneity, rather than innovative biological concepts about cellular states or heterogeneity. Any proposed biological assay(s) should be chosen strictly for utility (rather than biological novelty) in proof-of-concept testing of the innovative technique.

Preliminary/feasibility data are not required or expected for early-stage, high-risk projects. However, a sound rationale should be provided as to why the approach proposed is the most appropriate and likely to generate an exceptionally high impact if successful. In these cases, more emphasis should also be placed in details of the approach, particularly feasibility-testing.

Milestones

In lieu of a timeline, the Research Strategy should include a distinct final section, entitled Milestones , that briefly proposes indicators of progress at critical junctures. These should be tailored to the unique scope of each project and written concretely enough to evaluate what exactly will have been achieved (e.g., crucial steps in tool making) during the course of the project. Given that projects are likely to be early stage and high-risk in nature, this should include the specific proof-of-concept test(s) that will indicate whether/how a proposed tool actually works , along with alternative strategies should that effort fail to perform as expected. Tests should include a comparison against existing benchmark technologies; if a tool is truly first-in-class, comparisons may be done against a nearest neighbor technology. Investigators should briefly note how results will be used to inform future phases of tool development, validation or implementation beyond this R21 project. This section should be included within the page limit of the Research Strategy. If funded, investigators should describe progress toward milestones in the final report of the grant.

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 SF424 (R&R) Application Guide. While it is understood that many tools will be at an early proof-of-concept stage, a central goal of this FOA is to generate transformative tools that will be widely used throughout the research community to advance research in the field. Consistent with achieving the goals of this program, applications that propose to generate such tools are expected to include a detailed plan for sharing these resources and include the following key elements:

• Project management of resource sharing;
• Description of what specific resources would be shared (e.g., model organisms, reagents, completed tools or repurposable components thereof);
• Schedule/timeline for availability of resources to other users;
• Persons who would have access to the resources (written as broadly as possible to the extent consistent with applicable laws, regulations, rules, and policies);
• Plan for post-award disposition of resources.

Appendix

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

Foreign (non-US) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit in advance of the deadline to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications via Grants.gov, the online portal to find and apply for grants across all Federal agencies. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

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

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

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.

Applications must be submitted electronically following the instructions described in the SF 424 (R&R) Application Guide. Paper applications will not be accepted.

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

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF 424(R&R) Application Package. Failure to register in the Commons and to include a valid PD(s)/PI(s) Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

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

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness 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. Applications considered nonresponsive to this FOA include: generating tools that are duplicative or an incremental improvement of existing technologies; addressing a biological question as a main focus rather than as a proof-of-concept test of a new technology; studying single cell organisms (e.g., bacteria, yeast). While the main goal of this FOA is in situ application of technologies, in vitro approaches may be appropriate as a step in support of some studies. Applications to validate and translate technologies already demonstrated in practice should respond instead to the companion announcement RFA-RM-11-015.

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(s)/PI(s) 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.

For this particular announcement, note the following:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

NIH understands and accepts that early stage, high-risk/high-impact applications that are responsive to this solicitation will be much riskier than for most other R21 solicitations. Any scarcity in preliminary/feasibility data should be balanced by greater emphasis on rationale and approach. Reviewers should balance the risk with the likelihood of the new tools having an exceptionally high impact on the field, if successful. Reviewers should note that research designs are expected to focus on innovative tool development for in situ analysis of single cell heterogeneity, rather than innovative biological concepts about cellular states or heterogeneity. Therefore, any proposed biological assay(s) should have been chosen strictly for utility (rather than biological novelty) in proof-of-concept testing of the innovative technique.

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.

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? How will the project address barriers to single cell analysis in situ (e.g., explant, whole organism) that are due to the lack of tools to identify and target cells rigorously? How do the technical barriers relate to currently intractable scientific questions about cell heterogeneity, such that the application will transform the field by generating foundational resources (e.g., tools, methods) that will be widely used throughout the basic and translational research community?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If 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 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? How does developing the tool(s) provide a major change in practice from current methods for single cell analysis? To what extent do the tool(s) provide first-in-class, cross-cutting or significantly advanced capacity for single cell analysis of heterogeneity in situ (e.g., explant, whole organism)?

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?

How will the tools be made sufficiently sensitive, selective or appropriate for the intended use in single cell analysis in situ? How will the methodologies lead to a more rigorous distinction between potentially subtle cell subtypes, developmental stages and/or functional states (i.e., cell heterogeneity)? If using multiplex analysis, how effectively will multiple or cross-cutting approaches be utilized to characterize heterogeneous cellular states in a more integrative manner? If using computational approaches, how will they yield a more comprehensive systems-level view of cell heterogeneity by modeling or dataset analysis? In all applications, how well has a current benchmark technology been used to assess the relative utility of the new tool(s)? How rigorous is the proof-of-concept test of the tool(s) in a complex biological tissue or living organism? How useful are the proposed milestones (e.g., a crucial step in tool making, a specific proof-of-concept test) for definitively assessing the scientific accomplishments of the project and the functionality of the tool(s)?

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 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.

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 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

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). Since a central goal of this FOA is to generate transformative tools that will be widely used throughout the research community, applications that propose to generate such resources (e.g., new tools, reagents, methods) must include a detailed plan for sharing these resources. Reviewers will comment on whether relevant sharing plans adequately address key elements described in the Section IV instructions of this FOA..

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

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

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.

Cooperative Agreement Terms and Conditions of Award

Not Applicable.

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.

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading or navigating forms)
Contact Center Phone: 800-518-4726
Email: [email protected]

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]

David M. Panchision, Ph.D.
Division of Neuroscience and Basic Behavioral Science
National Institute of Mental Health
6001 Executive Boulevard, Room 7186, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-5288
Fax: (301) 451-5615
Email: [email protected]

David Balasundaram, Ph.D.
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 5136, MSC 7840
Bethesda, MD 20892-7840
Telephone: (301) 435-1022
Fax: (301) 480-1988
Email: [email protected]

James Huff
Grants Management Specialist
National Institute of Biomedical Imaging and Bioengineering, NIH
6707 Democracy Blvd. Suite 900
Bethesda, MD 20892-5469
Phone: 301-451-4786
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.