Part I Overview Information


Department of Health and Human Services

Participating Organizations
National Institutes of Health (NIH) (http://www.nih.gov)

Components of Participating Organizations
This FOA is developed as part of the NIH Roadmap Molecular Libraries and Imaging Initiative (http://nihroadmap.nih.gov/molecularlibraries/), in which all NIH Institutes and Centers participate.  The FOA will be administered by the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute of Mental Health (NIMH) on behalf of the NIH.   

Title:  Assay Development for High Throughput Molecular Screening (R21)

Announcement Type

This is a reissue of RFA-RM-07-001 , which was previously released July 13, 2006.

Update: The following update relating to this announcement has been issued:

NOTICE: Applications submitted in response to this Funding Opportunity Announcement (FOA) for Federal assistance must be submitted electronically through Grants.gov (http://www.grants.gov) using the SF424 Research and Related (R&R) forms and the SF424 (R&R) Application Guide. 

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the application guidelines included with this announcement in Grants.gov/Apply for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission and applicants are highly encouraged to start the process at least four weeks prior to the grant submission date. See Section IV.

Request For Applications (RFA) Number: RFA-RM-07-008   

Catalog of Federal Domestic Assistance Number(s)
93.310  

Key Dates
Release/Posted Date: March 16, 2007
Opening Date: April 16, 2007(Earliest date an application may be submitted to Grants.gov)     
Letters of Intent Receipt Date(s): May 2, 2007
NOTE: On time submission requires that applications be successfully submitted to Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization). 
Application Submission/Receipt Date(s):  May 16, 2007
Peer Review Date(s): July, 2007 
Council Review Date(s): August, 2007  
Earliest Anticipated Start Date(s): September 30, 2007
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: May 17, 2007

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
1. Research Objectives

Section II. Award Information
1. Mechanism of Support
2. Funds Available

Section III. Eligibility Information
1. Eligible Applicants

    A. Eligible Institutions
    B. Eligible Individuals
2. Cost Sharing or Matching
3. Other - Special Eligibility Criteria

Section IV. Application and Submission Information
1. Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Submission, Review, and Anticipated Start Dates
          1. Letter of Intent
    B. Submitting an Application Electronically to the NIH
    C. Application Processing
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
    A. Additional Review Criteria
    B. Additional Review Considerations
    C. Sharing Research Data
    D. Sharing Research Resources
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirement
3. Reporting

Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)

2. Peer Review Contact(s)
3. Financial/Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

This FOA is one component of the NIH Molecular Libraries and Imaging Roadmap Initiative (http://nihroadmap.nih.gov/molecularlibraries/index.asp), a major NIH effort to broaden access to rapid assay technologies.  The Assay Development for HTS Program will fund the development and adaptation of biological assays for use in molecular probe development projects employing automated high throughput molecular screening (HTS).  It is expected that screening projects developed within this FOA will, upon completion, be submitted to the Molecular Libraries Screening Centers Network (MLSCN;  http://mli.nih.gov/mlscn/index.php) for implementation.  This network has assembled a broad array of HTS capabilities which it employs to test small molecule chemical structures for interactions with biological targets.  The MLSCN has exclusive access to a library of compounds assembled for this purpose, the Molecular Libraries Small Molecule Repository. (http://mli.nih.gov/mlsmr/index.php). The overall goals of the Molecular Libraries and Imaging Roadmap Initiative are to facilitate expansion of the PubChem public database of biological information about small molecule chemical structures (http://pubchem.ncbi.nlm.nih.gov/), and the development of small molecule pharmacological tools for biological research.  Other efforts within the Initiative also supporting these objectives include the development of HTS-related technologies, Informatic applications and PreClinical tools.  A further component of this Roadmap Initiative, PAR-06-545 (http://grants.nih.gov/grants/guide/pa-files/PAR-06-545.html) solicits HTS-ready biological assay projects not requiring assay development for screening within the MLSCN.

High throughput molecular screening (HTS) is the automated, simultaneous testing of thousands of distinct chemical compounds in models of biological mechanisms.  Active compounds identified through HTS can provide the starting point in the design of powerful research tools that allow pharmacological probing of basic biological mechanisms, and which can be used to establish the role of a molecular target in a disease process, or, its ability to alter the metabolism or toxicity of a therapeutic agent.  The immense potential of HTS to impact our understanding of biological mechanisms is largely untapped because access to automated screening facilities and large compound libraries is limited in academic, government and non-profit research sectors. The NIH Molecular Libraries Roadmap Initiative now provides unprecedented access to these resources and will allow the broad application of HTS in NIH-supported research.

The goal of this FOA is to initiate a continuously evolving stream of scientifically and technologically outstanding assays that can be miniaturized, automated and further used for screening small molecules within the Molecular Libraries Screening Centers Network.  It is open to all areas of biological and biomedical research, with the goals of disseminating information about small molecule-target interactions via PubChem, and of catalyzing the development of pharmacological tools that can be used to probe biological processes.   Funding will be provided to allow investigators to develop promising assay protocols for novel molecular targets or phenotypes and transform them into automated screening projects by demonstrating the responsiveness and robustness required for their use in HTS.  An emphasis will be placed on the screening of targets for which an inadequate array of selective and potent small molecule modulators are available to the public

Screening projects prepared under this FOA are aimed at enabling the design of pharmacological tools to explore cellular and physiological function. Investigators are asked to state a question from their ongoing research that would be appropriately addressed through the use of a pharmacological probe.  Further, to identify the requisite attributes of this probe, and propose a screening plan of assays that would help them to find chemical small molecule structures possessing these attributes in a HTS of chemical small molecule libraries.  

Many in vitro biological models are currently used to study biological targets and pathways, the effects of genetic perturbations on their function, and to establish a possible disease association.  These models can be adapted to high throughput formats for the purpose of screening large collections of compounds with potential biological activity.  There are a number of characteristics that make an assay suitable for its adaptation to a high throughput approach. The assay must be robust, reproducible and have a readout that is amenable to automated analysis. In addition, the work proposed must lead to miniaturization of the assay to a 96-well plate (or higher density) format or translation to a flow-cytometric approach.  Further, the assay protocol should be simple enough for automated handling.  A broad range of models share many of these features, including; biochemical assays, cellular models and certain model organisms.  This FOA will support the adaptation of innovative assays that can be used to isolate small molecule chemical structures with biological activity, and support the development of  pharmacological probes.  The molecular probes that result will aid research that is aimed at understanding basic biological processes, and promoting an understanding of disease mechanisms.  An emphasis will be placed on novelty of assay approach and/or novel targets and mechanisms.  Appropriate assays might include but are not limited to:

The FOA is divided into two aims: A) Assay Development.  B) Configuration of Assays for HTS.  Proposals for funding under the R21 mechanism would be expected to span both aims, although more advanced proposals that are limited in scope to Aim B will also be considered. 

Plans for Assay Development must include the following information:

Plans to Configure Assays for HTS must include the following information:

The applicant must anticipate the use of the assay in a high throughput screening project by providing a clear plan for evaluating the significance of active compounds obtained. The plan must include plans to develop (as needed) and use secondary screens to confirm compounds active in the primary screen as reproducible hits, and rule out artifacts (to include dose-ranging experiments, and assays which measure a different activity than employed in the primary assay).  Plans to develop (as needed) and use counter-screening assays should also be described that allow prioritization of these hits for further testing (for example, on the basis of selectivity or potential toxicity).  It is likely that a few hundred active compounds may be identified in a primary HTS effort; therefore the screening plan should show that an evaluation of these hits is feasible.

Assay development supported through the R21 mechanism will be funded in year 1 with up to $100,000 in direct costs (excluding consortium F&A costs).  Projects funded with the R21 mechanism will emphasize the development of highly innovative assays and the assembly of a viable HTS project plan. Some degree of risk is acceptable, particularly if innovation is high.  However, it is expected that preliminary data will be provided in the application demonstrating that the proposed assay(s) can be developed, configured and validated within the project period.  In addition, experimental plans aimed at providing validation data supporting a HTS strategy for molecular probe development under the award must be well defined in the application.

Support for implementation of the assay project in the MLSCN will be provided in year 2 via the R21 mechanism with up to $25,000 in direct costs (excluding consortium F&A).  The development and adaptation of screening assays facilitated by this FOA will lead to the preparation of screening projects that are ready for final assay development and HTS implementation.  It is expected that these projects will be submitted to the NIH Roadmap Molecular Libraries Screening Centers Network (MLSCN) in year 2 of the award. However, funding under this FOA does not carry a commitment by NIH to accept the assay projects for screening.  Projects accepted by the MLSCN will receive up to  $25,000 support in direct costs (excluding consortium F&A) for collaboration with the assigned Screening Center on screening project implementation and folllow-up activities.

Please Note the Following Information about MLSCN entry: Assay development projects funded under this FOA, following completion, can request direct “Fast-Track” entry into the MLSCN.  A technical review of progress reports will then be made by the NIH Roadmap Molecular Libraries Project Team prior to acceptance of the screening project. In addition to the required project report, investigators are asked to provide assay characterization data, and to address the following technical feasibility questions: 1) Are the proposed screening assays feasible in HTS format? 2) Is the screening plan complete? 3) Are key reagents required for execution of the HTS project available? 4) What is the current availability of pharmacological probes to the proposed target, mechanism or phenotype?  Collaboration activities between the Investigator and assigned Screening Center will be agreed following acceptance of the HTS project, and may include: Travel to the screening center.  Hit follow-up in the Investigators laboratory using secondary and counter-screening assays developed by the Investigator as part of the screening project.  The further preparation of reagents required for the HTS.

Additional information about the criterion for acceptance of projects to the MLSCN, and its policies for data sharing, is detailed in the separate assay solicitation announcement  PAR-06-545 (http://grants.nih.gov/grants/guide/pa-files/PAR-06-545.html)..

See Section VIII, Other Information - Required Federal Citations, for policies related to this announcement.

Section II. Award Information


1. Mechanism of Support

This Funding Opportunity Announcement (FOA) will use a modified R21 award mechanism. Direct costs for year one are limited to $100,000 (excluding consortium F&A costs).  Direct costs for year two may not exceed $25,000 (excluding consortium F&A costs), and are available only to projects entering the Molecular Libraries Screening Center Network (http://mli.nih.gov/mlscn/index.php).

The applicant will be solely responsible for planning, directing, and executing the proposed project.

This FOA uses just-in-time concepts. It also uses the modular as well as the non-modular  budget formats (see the “Modular Applications and Awards” section of the NIH Grants Policy Statement. Specifically, if you are submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities and Administrative [F&A] costs), use the PHS398 Modular Budget component provided in the SF424 (R&R) Application Package and SF424 (R&R) Application Guide (see specifically Section 5.4, “Modular Budget Component,” of the Application Guide).

All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096, August 23, 2006.

Competing renewal (formerly competing continuation) applications will not be accepted for this FOA. At this time, it is not known if this FOA will be reissued.

2. Funds Available

Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary. Although the financial plans of the Institutes and Centers (ICs) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

The total project period for an application submitted in response to this funding opportunity may not exceed two years. Although the size of award may vary with the scope of research proposed, it is expected that applications will stay within the budgetary guidelines for an exploratory/developmental project. Direct costs are limited to $100,000 over the first year of the award (excluding consortium F&A costs). Direct costs in year two are limited to $25,000 (excluding consortium F&A costs), and are available only to projects entering the Molecular Libraries Screening Center Network.   Applicants may request direct costs in $25,000 modules, up to the specified limitation, to reflect the scope of the proposed work.  

NIH grants policies as described in the NOT-OD-05-004, November 2, 2004.

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

You may submit an application(s) if your organization has any of the following characteristics:

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach that clearly does not fit the single-PD/PI model. Additional information on the implementation plans and policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to apply for a single PD/PI or multiple PD/PI grant is the responsibility of the investigators and applicant organizations and should be determined by the scientific goals of the project. Applications for multiple PD/PI grants will require additional information, as outlined in the instructions below. The NIH review criteria for approach, investigators, and environment have been modified to accommodate applications involving either a single PD/PI or multiple PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PD/PIs will be factored into the assessment of the overall scientific merit of the application.  Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.

2. Cost Sharing or Matching

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

3. Other-Special Eligibility Criteria

Relevance to the goals of the FOA described under Section I, Research Objectives, will be considered in accepting applications for review.  Applications that do not meet the goals and defined scope of developing and validating assays for use in a high throughput small molecule screening project will not be reviewed.  

Applicants may submit more than one application, provided each application is scientifically distinct.

Section IV. Application and Submission Information


To download a SF424 (R&R) Application Package and SF424 (R&R) Application Guide for completing the SF424 (R&R) forms for this FOA, link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

A one-time registration is required for institutions/organizations at both:

PD/PIs should work with their institutions/organizations to make sure they are registered in the eRA Commons.

Several additional separate actions are required before an applicant institution/organization can submit an electronic application, as follows:

1) Organizational/Institutional Registration in Grants.gov/Get Started

2) Organizational/Institutional Registration in the eRA Commons

3) Project Director/Principal Investigator (PD/PI) Registration in the NIH eRA Commons: Refer to the NIH eRA Commons System (COM) Users Guide.

Both the PD/PI(s) and AOR/SO need separate accounts in the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with an Individual DUNS and CCR registration, that particular DUNS number and CCR registration are for the individual reviewer only. These are different than any DUNS number and CCR registration used by an applicant organization. Individual DUNS and CCR registration should be used only for the purposes of personal reimbursement and should not be used on any grant applications submitted to the Federal Government.

Several of the steps of the registration process could take four weeks or more. Therefore, applicants should immediately check with their business official to determine whether their organization/institution is already registered in both Grants.gov and the Commons. The NIH will accept electronic applications only from organizations that have completed all necessary registrations.

1. Request Application Information

Applicants must download the SF424 (R&R) application forms and SF424 (R&R) Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package directly attached to a specific FOA can be used. You will not be able to use any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA), although some of the "Attachment" files may be useable for more than one FOA.

For further assistance, contact GrantsInfo: Telephone 301-435-0714, Email: GrantsInfo@nih.gov.

Telecommunications for the hearing impaired: TTY 301-451-5936.

2. Content and Form of Application Submission

Prepare all applications using the SF424 (R&R) application forms and in accordance with the SF424 (R&R) Application Guide for this FOA through Grants.gov/APPLY.

The SF424 (R&R) Application Guide is critical to submitting a complete and accurate application to NIH. There are fields within the SF424 (R&R) application components that, although not marked as mandatory, are required by NIH (e.g., the “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component must contain the PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for such fields are clearly identified in the Application Guide. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

The SF424 (R&R) application is comprised of data arranged in separate components. Some components are required, others are optional. The forms package associated with this FOA in Grants.gov/APPLY will include all applicable components, required and optional. A completed application in response to this FOA will include the following components:

Required Components:
SF424 (R&R) (Cover component)
Research & Related Project/Performance Site Locations
Research & Related Other Project Information
Research & Related Senior/Key Person
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist
PHS398 Modular Budget or Research & Related Budget, as appropriate (See Section IV.6., “Special Instructions,” regarding appropriate required budget component.) 
Research & Related Budget (required for foreign applications)

Optional Components:
PHS398 Cover Letter File
Research & Related Subaward Budget Attachment(s) Form

Foreign Organizations (Non-domestic (non-U.S.) Entity)

NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600260.

Applications from foreign organizations must:

Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.

SPECIAL INSTRUCTIONS  

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the "Contact” PI, who will be responsible for all communication between the PDs/PIs and the NIH, for assembling the application materials outlined below, and for coordinating progress reports for the project. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs, but has no other special roles or responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in item 15 of the SF424(R&R) Cover component. All other PDs/PIs should be listed in the Research & Related Senior/Key Person component and assigned the project role of “PD/PI.” Please remember that all PDs/PIs must be registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research & Related Senior/Key Person component. Failure to include this data field will cause the application to be rejected.

All projects proposing Multiple PDs/PIs will be required to include a new section describing the leadership of the project.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new section of the research plan, entitled “Multiple PD/PI Leadership Plan” (Section 14 of the Research Plan Component in the SF424 (R&R)), must be included. A rationale for choosing a multiple PD/PI approach should be described.  The governance and organizational structure of the leadership team and the research project should be described, including communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators. 

If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan.  In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution, follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions 

When multiple institutions are involved, one institution must be designated as the prime institution and funding for the other institution(s) must be requested via a subcontract to be administered by the prime institution. When submitting a detailed budget, the prime institution should submit its budget using the Research & Related Budget component. All other institutions should have their individual budgets attached separately to the Research & Related Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R) Application Guide for further instruction regarding the use of the subaward budget form. 

When submitting a modular budget, the prime institution completes the PHS398 Modular Budget component only. Information concerning the consortium/subcontract budget is provided in the budget justification. Separate budgets for each consortium/subcontract grantee are not required when using the Modular budget format. See Section 5.4 of the Application Guide for further instruction regarding the use of the PHS398 Modular Budget component.

3. Submission Dates and Times

See Section IV.3.A for details.

3.A. Submission, Review, and Anticipated Start Dates

Opening Date: April 16, 2007  (Earliest date an application may be submitted to Grants.gov)     
Letters of Intent Receipt Date: May 2, 2007
Application Submission Date(s): May 16, 2007  
Peer Review Date(s): July, 2007 
Council Review Date(s): August, 2007
Earliest Anticipated Start Date: September 30, 2007

3.A.1. Letter of Intent

Prospective applicants are asked to submit a letter of intent that includes the following information:

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.

The letter of intent is to be sent by the date listed in Section IV.3.A.

The letter of intent should be sent to:

Mark Scheideler, Ph.D. 
Program Director, Molecular Libraries
Technology Development, NINDS
National Institutes of Health
6001 Executive Blvd., Room 2107
Rockville, MD 20852 (Express Mail )  
Bethesda, MD 20892-9527
Telephone: (301) 496-1779
Fax: (301) 402-1501
Email:  scheidelerm@ninds.nih.gov   

3.B. Submitting an Application Electronically to the NIH

To submit an application in response to this FOA, applicants should access this FOA via http://www.grants.gov/Apply and follow steps 1-4. Note:  Applications must only be submitted electronically.  PAPER APPLICATIONS WILL NOT BE ACCEPTED. 

In order to expedite the review, applicants are requested to notify the NIMH Referral Office by email nimhreferral@mail.nih.gov when the application has been submitted.  Please include the FOA number and title, PD/PI name, and title of the application.

3.C. Application Processing

Applications may be submitted on or after the opening date and must be successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt date(s) and time, the application may be delayed in the review process or not reviewed.

Once an application package has been successfully submitted through Grants.gov, any errors have been addressed, and the assembled application has been created in the eRA Commons, the PD/PI and the Authorized Organization Representative/Signing Official (AOR/SO) have two business days to view the application image.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review, NIH. Incomplete applications will not be reviewed.

There will be an acknowledgement of receipt of applications from Grants.gov and the Commons. Information related to the assignment of an application to a Scientific Review Group is also in the Commons. 

The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted in response to a previous FOA for this program, is to be submitted in response to this funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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

Pre-award costs are allowable. A grantee may, at its own risk and without NIH prior approval, incur obligations and expenditures to cover costs up to 90 days before the beginning date of the initial budget period of a new award if such costs: are necessary to conduct the project, and would be allowable under the grant, if awarded, without NIH prior approval. If specific expenditures would otherwise require prior approval, the grantee must obtain NIH approval before incurring the cost. NIH prior approval is required for any costs to be incurred more than 90 days before the beginning date of the initial budget period of a new award.

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See the NIH Grants Policy Statement.

6. Other Submission Requirements

PD/PI Credential (e.g., Agency Login)

The NIH requires the PD/PI to fill in his/her Commons User ID in the “PROFILE – Project Director/Principal Investigator” section, “Credential” log-in field of the “Research & Related Senior/Key Person Profile” component. The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Registration FAQs – Important Tips -- Electronic Submission of Grant Applications.”

Organizational DUNS

The applicant organization must include its DUNS number in its Organization Profile in the eRA Commons. This DUNS number must match the DUNS number provided at CCR registration with Grants.gov. For additional information, see “Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

PHS398 Research Plan Component Sections

While each section of the Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to better monitor formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.   

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, incorporating "Just-in-Time" information concepts.

Appendix Materials

Applicants must follow the specific instructions on Appendix materials as described in the SF424 (R&R) Application Guide See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Do not use the Appendix to circumvent the 10 page limitation of the Research Plan component. The Research Plan should include all information of relevance to the proposed science, including preliminary data, references and publications. An application that does not observe the relevant policies and procedures may be delayed in the review process.

Note: While each section of the PHS398 Research Plan component needs to be uploaded separately as a PDF attachment, applicants are encouraged to construct the Research Plan component as a single document, separating sections into distinct PDF attachments just before uploading the files. This approach will enable applicants to monitor better formatting requirements such as page limits. All attachments must be provided to NIH in PDF format, filenames must be included with no spaces or special characters, and a .pdf extension must be used.

SUPPLEMENTARY INSTRUCTIONS:

The following exceptions to the general R21 instructions will apply for this FOA:

Foreign Applications (Non-domestic (non-U.S.) Entity)

Plan for Sharing Research Data

The precise content of the data-sharing plan will vary, depending on the data being collected and how the investigator is planning to share the data. Applicants who are planning to share data may wish to describe briefly the expected schedule for data sharing, the format of the final dataset, the documentation to be provided, whether or not any analytic tools also will be provided, whether or not a data-sharing agreement will be required and, if so, a brief description of such an agreement (including the criteria for deciding who can receive the data and whether or not any conditions will be placed on their use), and the mode of data sharing (e.g., under their own auspices by mailing a disk or posting data on their institutional or personal website, through a data archive or enclave). Investigators choosing to share under their own auspices may wish to enter into a data-sharing agreement. References to data sharing may also be appropriate in other sections of the application.

All applicants must include a plan for sharing research data in their application. The data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible.

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score.

Submission of the results of the pilot compound screening funded by this FOA to the NIH PubChem database (http://pubchem.ncbi.nlm.nih.gov/) is a requirement of the award.  

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement  http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590). See Section VI.3., “Reporting.”

Applicants should specify how research methodologies developed in the context of the funded research will be made available.  Applicants submitting screening projects to the MLSCN in year two of the award should refer to the MLSCN solicitation announcement PAR-06-545 for guidance on MLSCN policy for sharing research resources (http://grants.nih.gov/grants/guide/pa-files/PAR-06-545.html).

Section V. Application Review Information


1. Criteria 

Only the review criteria described below will be considered in the review process.

2. Review and Selection Process

Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NIMH in accordance with the review criteria stated below.

As part of the initial merit review, all applications will:

Applications submitted in response to this funding opportunity will compete for available funds with all other recommended applications. The following will be considered in making funding decisions:

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application.

Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge or clinical practice be advanced? What will be the effect of these studies on the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?  Are there important and well-defined goals for the use of active compounds identified with the proposed assay as research tools?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics?  Is it feasible to adapt the proposed assay to a HTS format?  Is it likely that the assay will produce reliable results in a high throughput screen?  Is there an adequate plan for evaluating the activities of the compounds identified in a high throughput screen, e.g., in secondary assays and counter-screening assays? For applications designating multiple PDs/PIs, does the Leadership Plan ensure that there will be sufficient coordination and communication among the PDs/PIs?  Are the administrative plans for the management of the research project appropriate, including plans for resolving conflicts?    

Innovation: Is the project original and innovative? For example: Does the project challenge existing paradigms or clinical practice; address an innovative hypothesis or critical barrier to progress in the field? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area? Is the molecular target or mechanism proposed for study highly novel?

Investigators: Are the PD/PI(s) and other key personnel appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the PD/PI and other researchers? Does the PD/PI(s) and investigative team bring complementary and integrated expertise to the project (if applicable)? Is the submitting PI a new investigator?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment, or subject populations, or employ useful collaborative arrangements? Is there evidence of institutional support?

2.A. Additional Review Criteria:

In addition to the above criteria, the following items will continue to be considered in the determination of scientific merit and the priority score:

Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed. See the “Human Subjects Sections” of the PHS398 Research Plan component of the SF424 (R&R).

Care and Use of Vertebrate Animals in Research:
If vertebrate animals are to be used in the project, the adequacy of the plans for their care and use will be assessed. See the “Other Research Plan Sections” of the PHS398 Research Plan component of the SF424 (R&R). 

Biohazards: If materials or procedures are proposed that are potentially hazardous to research personnel and/or the environment, determine if the proposed protection is adequate.

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the appropriateness of the requested period of support in relation to the proposed research may be assessed by the reviewers. The priority score should not be affected by the evaluation of the budget. Is the percent effort listed for the PD/PI appropriate for the work proposed? Is each budget category realistic and justified in terms of the aims and methods?

Applications from Foreign Organizations: Whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources will be assessed. 

2.C. Sharing Research Data

The reasonableness of the data sharing plan or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor the proposed data sharing plan into the determination of scientific merit or the priority score. The presence of a data sharing plan will be part of the terms and conditions of the award. The funding organization will be responsible for monitoring the data sharing policy. Submission of the results of the pilot compound screening funded by this FOA to the NIH PubChem database (http://pubchem.ncbi.nlm.nih.gov/) is a requirement of the award.  

2.D. Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement  http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

Program staff will be responsible for the administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each Non-Competing Grant Progress Report (PHS 2590), See Section VI.3., “Reporting.”

Model Organism Sharing Plan:  Reviewers are asked to assess the sharing plan in an administrative note. The sharing plan itself should be discussed after the application is scored. Whether a sharing plan is reasonable can be determined by the reviewers on a case-by-case basis, taking into consideration the organism, the timeline, the applicant's decision to distribute the resource or deposit it in a repository, and other relevant considerations.

3. Anticipated Announcement and Award Dates

Not Applicable

Section VI. Award Administration Information


1. Award Notices

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the NIH eRA Commons

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official.

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. See Section IV.5., “Funding Restrictions.”       

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General  and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities.

3. Reporting

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

Assay development projects funded under this FOA, following completion, can request direct “Fast-Track” entry into the MLSCN.  A technical review of year one progress reports will then be made by the NIH Roadmap Molecular Libraries Project Team prior to acceptance of the screening project. In addition to the required project report, investigators are asked to provide assay characterization data, and to address the following technical feasibility questions: 1) Are the proposed screening assays feasible in HTS format? 2) Is the screening plan complete? 3) Are key reagents required for execution of the HTS project available? 4) What is the current availability of pharmacological probes to the proposed target, mechanism or phenotype?  Projects accepted for screening by the MLSCN will then be eligible for $25,000 in direct costs (excluding consortium F&A) in year two of the R21 for collaboration with the assigned Screening Center.  Collaboration activities will be agreed with the assigned Screening Center following acceptance of the HTS project, and may include: Travel to the screening center.  Hit follow-up in the Investigators laboratory using secondary and counter-screening assays developed by the investigator as part of the screening project.  The further preparation of reagents required for the HTS.

Section VII. Agency Contacts


We encourage your inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants. Inquiries may fall into three areas: scientific/research, peer review, and financial or grants management issues:

1. Scientific/Research Contacts:

Mark Scheideler, Ph.D.
Program Director, Molecular Libraries
Technology Development, NINDS
National Institutes of Health
6001 Executive Blvd., Room 2107
Rockville, MD 20852 (Express Mail)                                                               
Bethesda, MD 20892-9527 (Regular Mail)  
Telephone: (301) 496-1779
Fax: (301) 402-1501
Email: scheidelerm@ninds.nih.gov

2. Peer Review Contacts:

Yong Yao , Ph.D.
Scientific Review Branch
National Institute of Mental Health
Room 6149, MSC 9608 6001
Executive Boulevard Bethesda , MD 20892-9608
(Rockville , MD 20852 for express/courier service)
Telephone: (301) 443-6102
Fax: (301) 402-0182
E-mail: nimhreferral@mail.nih.gov
 
3. Financial or Grants Management Contacts:

Pamela L. Mayer
Grants Management Analyst
Grants Management Branch
National Institute of Neurological Disorders and Stroke/NIH/DHHS
6001 Executive Boulevard, Sui te 3290, MSC 9537
Rockville, MD 20852 (Express Mail)
Bethesda , MD 20892-9537 (Regular Mail)
Branch Phone Number: (301) 496-9231
Fax Number: 301-402-0219
Email: mayerp@ninds.n ih.gov

Section VIII. Other Information


Required Federal Citations

Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.

Human Subjects Protection:
Federal regulations (45 CFR 46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule. Reviewers will consider the data sharing plan but will not factor the plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of Information Act:
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this funding opportunity in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award.

Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement. Beginning October 1, 2004, all investigators submitting an NIH application or contract proposal are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.

Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-005.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research. Applications that do not provide this information will be returned without review.

NIH Public Access Policy:
NIH-funded investigators are requested to submit to the NIH manuscript submission (NIHMS) system (http://www.nihms.nih.gov) at PubMed Central (PMC) an electronic version of the author's final manuscript upon acceptance for publication, resulting from research supported in whole or in part with direct costs from NIH. The author's final manuscript is defined as the final version accepted for journal publication, and includes all modifications from the publishing peer review process.

NIH is requesting that authors submit manuscripts resulting from 1) currently funded NIH research projects or 2) previously supported NIH research projects if they are accepted for publication on or after May 2, 2005. The NIH Public Access Policy applies to all research grant and career development award mechanisms, cooperative agreements, contracts, Institutional and Individual Ruth L. Kirschstein National Research Service Awards, as well as NIH intramural research studies. The Policy applies to peer-reviewed, original research publications that have been supported in whole or in part with direct costs from NIH, but it does not apply to book chapters, editorials, reviews, or conference proceedings. Publications resulting from non-NIH-supported research projects should not be submitted.

For more information about the Policy or the submission process, please visit the NIH Public Access Policy Web site at http://publicaccess.nih.gov/ and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for Privacy of Individually Identifiable Health Information:
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, Internet addresses (URLs) or PubMed Central (PMC) submission identification numbers must be used for publicly accessible on-line journal articles. Publicly accessible on-line journal articles or PMC articles/manuscripts accepted for publication that are directly relevant to the project may be included only as URLs or PMC submission identification numbers accompanying the full reference in either the Bibliography & References Cited section, the Progress Report Publication List section, or the Biographical Sketch section of the NIH grant application. A URL or PMC submission identification number citation may be repeated in each of these sections as appropriate. There is no limit to the number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:
The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS-led national activity for setting priority areas. This FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. 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. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.

Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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