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 Funding Opportunity Announcement (FOA) is developed as an NIH roadmap initiative (http://nihroadmap.nih.gov).  All NIH Institutes and Centers participate in roadmap initiatives. The FOA will be administered by the National Institute of Mental Health (NIMH) on behalf of the NIH.

Title: Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (R03)

Announcement Type
This is a reissue and modification of PAR-05-060 that expired on May 18, 2006. This FOA is being reissued to provide up to $25,000 total costs for each award instead of $3,000 direct costs.  New applications require electronic submission through Grants.gov using SF424 (R&R) forms. Programmatic aspects of the original announcement remain the same.  

Update: The following updates relating to this announcement have 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.

Program Announcement (PA) Number: PAR-06-545

Catalog of Federal Domestic Assistance Number(s)  
93.
310  

Key Dates
Release/Posted Date: September 7, 2006
Opening Date:  September 7, 2006 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date(s): Sept 26, 2006; Jan 26, 2007; May 26, 2007 and Sept 26, 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):  Oct 26, 2006; Feb 26, 2007; Jun 26, 2007 and Oct 26, 2007
Peer Review Date(s): December 2006; April 2007; August 2007 and December 2007.    
Council Review Date(s): May 2007; September 2007; January 2008 and May 2008.
Earliest Anticipated Start Date(s): June 2007; October 2007; February 2008 and June 2008.
Additional Information To Be Available Date (Activation Date): Not Applicable
Expiration Date: October 27, 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 Requirements
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

The National Institutes of Health (NIH) is committed to a major effort to broaden access to high-throughput screening (HTS) technologies, and the information produced by these approaches, for researchers in academia, government, and non-profit institutions. The public sector has not yet taken advantage of the considerable potential of HTS to advance the understanding of biology and disease mechanisms because access by academic scientists to automated screening facilities and diverse compound libraries is very limited. The NIH Molecular Libraries and Imaging Roadmap initiative has launched the Molecular Libraries Screening Centers Network (MLSCN) on June 15, 2005, which aims to enable the rapid transformation of new scientific knowledge into tangible benefits for public health. This effort will empower multi-disciplinary academic teams to discover small molecule tools that can be used in basic biological and biomedical studies. Descriptions of the ten network screening centers and their capabilities are available at http://nihroadmap.nih.gov/molecularlibraries/fundedresearch.asp

The NIH wishes to enhance access to HTS capabilities for the academic community in order to speed the discovery of molecular research tools (e.g., ligands, imaging probes, and new activities of existing drugs) that will be available to the public sector. It is also anticipated that this MLSCN effort will catalyze scientific breakthroughs that will contribute to the identification of molecular entities or molecular classes that may accelerate the development of therapeutics by the private sector. Through this approach, NIH wishes to stimulate research in the following areas: 1) discovery of novel biological targets that can inform studies of cell function and disease mechanisms; 2) development, validation, and application of screening assays and disease models to evaluate the activity of novel small molecules; and 3) use of chemical genomic approaches to characterize the biology of genes of interest, cellular processes, and proteins associated with disease processes.

The MLSCN is a collaborative research network that is comprised of nine extramural centers and one NIH intramural screening center. HTS assays will be selected for implementation in the MLSCN from those submitted by the research community in response to the Program Announcement “Solicitation of Assays for High Throughput Screening (HTS) in the Molecular Libraries Screening Centers Network (MLSCN).” Each screening center will implement innovative HTS approaches to identify compounds that are active in target-based and phenotypic assays using 96-well, 384-well or 1536-well plate formats, as appropriate to the specific assay and screening platform.

As a national research resource, the MLSCN interfaces with other components of the Molecular Libraries Roadmap initiative, including the Molecular Libraries Small Molecule Repository, PubChem, and ongoing initiatives for cheminformatics and for technology development in the areas of assay development, chemical diversity, screening instrumentation, and algorithms for predicting biological activity of small molecules. The Small Molecule Repository will acquire and maintain a collection of up to 500,000 compounds, from compound providers representing both commercial and academic sources, with well-known or unknown biological activities and diverse chemical structures. The repository will provide compounds to the screening centers for HTS. Within the MLSCN to the extent resources will allow it, HTS hits, the active compounds identified through initial screening, will be developed through optimization chemistry and further screening into useful bioactive probes that can be used by the scientific community to study molecular targets, cellular pathways, and potentially as starting points for drug development that will occur outside the MLSCN. The chemical structures of the compounds in the Small Molecule Repository, along with the related screening data, and assay protocols generated by the MLSCN will be deposited into a public database, PubChem. Information about the bioactive compounds will be made available to all researchers, who will be free to adapt them in biological and biomedical research studies. Early stage HTS assay developments are supported by the Assay Development for High Throughput Molecular Screening (R21).

Objectives of the Project

The objective of this FOA is to promote and support discovery and development of new chemical probes as research tools for use by scientists in both the public and private sector to advance the understanding of biological functions and disease mechanisms.  The MLSCN offers biomedical researchers the access to large-scale automated screening centers, diverse compound libraries and information on biological activities of small molecules

This FOA provides an opportunity to identify compounds that regulate proteins and pathways of interest to the research community.  Investigators interested in identifying active compounds in their biochemical and cellular assays and in developing chemical probes useful to the broader scientific community should submit a proposal for access to the screening, informatics and synthetic chemistry resources provided by the MLSCN. The proposal must provide a description of a well-developed assay that can be automated for HTS and a systematic plan, including secondary and counter-screening assays, for evaluating active compounds identified in the primary HTS. The proposal should also include a strategy for further testing, in collaboration with the MLSCN center and compound providers, to provide a final refinement in structure and function of the active compounds leading to the optimum chemical probe.

Services Provided by the MLSCN

The MLSCN will provide the following services for those assays selected for implementation in this program.

1. Assay Implementation: The MLSCN will adapt, optimize and automate existing target-based and cell-based phenotypic assays obtained from the scientific community to 96-well, 384-well or 1536-well plate format as appropriate to the specific assay, screening approach, and level of throughput anticipated. The MLSCN will be capable of implementing assays using a variety of detection readouts such as absorbance, fluorescence, luminescence, fluorescence energy transfer (FRET), bioluminescence resonance energy transfer (BRET), biophysical readouts, and cell based imaging screens.

2. Compound Library: The Small Molecule Repository is expected to have a collection of 100,000 compounds by December 2006 and will continue to grow to about 500,000 compounds through careful selection of both commercial and donated natural product and synthetic compounds to provide a library of diverse chemical structures of high purity that meet preset restrictions on solubility, number of reactive groups and compound size.  The repository will maintain these compounds under strict storage conditions and periodically distribute them to the MLSCN screening centers. The chemical structures of the compounds in the repository can be accessed at PubChem Substance under MLSMR.

3. HTS Screening: The MLSCN will screen the repository compounds for biological activity in HTS assays to identify and confirm HTS hits. The MLSCN center will work closely with the assay provider to define secondary assays used to verify these hits and identify false-positives. Screening data from both primary and secondary assays performed by the MLSCN will be deposited in PubChem BioAssay under the Depositor Category,Molecular Libraries Screening Center Network”.

4. Optimization Chemistry: Although the primary goal of the MLSCN is the identification and development of novel chemical probes, the MLSCN can not guarantee that every assay will lead to discovery of a chemical probe.  Following hit verification, the assay provider, compound provider, MLSCN screening center and NIH Science Officer will work as a team to define the best course of action to optimize the initial hits. The MLSCN will provide cheminformatics and optimization chemistry to produce analogues of initial hit compounds to identify a chemical probe demonstrating the best properties of potency, specificity and solubility.

5. HTS Informatics: The MLSCN will provide informatics support to track compounds, assays, and screening data. PubChem will support investigators with information for obtaining active compounds for their use in further research by identifying a source for purchase or synthesis of particular compounds. Any users of the data deposited into PubChem will be required to acknowledge the source of the data.

Guidance for HTS Assay Application

HTS is rapid screening of a large number of compounds in a biological assay.  Through a combination of modern robotics, data processing and control software, liquid handling devices, and sensitive detectors, HTS allows a researcher to effectively conduct millions of biochemical, genetic or pharmacological tests in a short period of time.  Through this process one can rapidly identify active compounds which modulate a particular biomolecular pathway.  The results of these experiments provide starting points for understanding the interaction or role of a particular biochemical process in biology. Since assays accepted by the MLSCN will be involved in high-throughput, robotic testing of compounds from the repository, the assays submitted should be adaptable to HTS with reasonable effort. It is anticipated that many of these assays will need to undergo further development to be usable in HTS formats, and such development will be accomplished through joint efforts between the submitting investigator and the MLSCN screening center that is selected to implement the assay. Assay applications will be evaluated in terms of the following characteristics:

1. Readiness for or adaptability to HTS: HTS assays are primarily characterized by miniaturization and automation, and are usually conducted in microtiter plates, such as 96-well, 384-well or 1536-well plates. Assays submitted for HTS should be well established and characterized. If achievable, assays should have simple procedures readily adaptable to automation. Steps such as centrifugation, filtration and extraction should be avoided. Homogeneous, i.e. “mix and measure,” assays are preferable.

2. Assay performance and robustness: Performance characteristics of an assay should be suitable and reliable for automated HTS. Assays should be robust, reproducible and meet minimum statistical thresholds for robotic screening. Robustness is a measure of the capacity of the assay to remain unaffected by small changes in method parameters and provides an indication of its reliability during normal run conditions. The Z’-factor, a calculated parameter, is commonly used to quantify assay performance, and it accounts for both the signal-to-background and the amount of variability in the assay. Assays with Z’ parameters >0.5 are typically HTS compatible assays. The coefficient of variation (CV) determined from the entire sample and control wells of the microtiter plate should not exceed 10%. Reproducibility between plates and day-to-day experiments also provides useful information on how well the assay will perform.

3. Diversity of assay types: Assays developed for HTS can be roughly characterized as target-based or phenotypic assays. A biological target is a macromolecule or a set of macromolecules in a biochemical pathway. Phenotypic assays measure a signal which corresponds to a complex response such as cell survival, proliferation, localization of a protein, nuclear translocation etc. The molecular target is not assumed in a phenotypic assay.

The following are some examples of HTS assays: 1) target-based biochemical assays may include enzymatic assays (such as kinases, proteases and transferases), and receptor-ligand binding assays such as those for G-protein coupled receptors (GPCRs), orphan GPCRs, ion channels, transporters, nuclear receptors, and new targets emerging from genetic and proteomic research in model systems and in human diseases; 2) cell-based assays could include functional assays, reporter gene assays and phenotypic assays for cellular processes and pathway analysis (e.g., viability assays for proliferation or apoptosis); 3) non-traditional targets of interest include transcription factors, nucleic acids, multimeric proteins, membrane proteins, and polymorphic gene products; and subcellular processes such as molecular trafficking and translocation, post-transcriptional editing or splicing of gene products, and protein or RNA stabilization; and 4) other assays of interest include those for metabolism, bioavailability, cytotoxicity, tissue permeability and compound solubility.

To learn more about HTS assay development, please refer to the online comprehensive guidebook “Guidance for Assay Development and HTS. Additional resources include: the “ASSAY and Drug Development Technologies”, a peer-reviewed bimonthly journal that publishes articles, papers, and editorial commentary that emphasize early-stage screening techniques including assay design, target development, high throughput technologies, and the Journal of Biomolecular Screening, the official Journal of the Society for Biomolecular Screening.

Material and Data Sharing

Submitting investigators will be required to provide necessary and sufficient reagents such as purified protein, cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g., a known inhibitor of the target).

Investigators are required to adopt uniform policies for data sharing and procedures recommended by the MLSCN committee. All data generated by the MLSCN will be deposited into PubChem upon data verification. For purposes of this policy, the term “data” will include, but will not be limited to, assay descriptions, protocols and/or links to published assays implemented in the MLSCN; performance data for assays and compounds; primary data from HTS and data generated in the secondary screen (e.g., EC50s, IC50s, AC50s, counter screens);chemical structures, synthesis protocols, and/or links to published synthesis protocols for chemical analogs of hits, for probes, and the biological activity of analogues and chemical probes. PubChem is a public database through which the MLSCN data will be available to all researchers, in both the public and private sectors, for further use in studying biology and disease.

For the MLSCN Project Team Policy on Data Sharing and IP in the MLSCN Program, see http://www.nimh.nih.gov/dnbbs/datasharing-ip.pdf. See details of NIH data sharing guidance http://grants1.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html

Project Oversight

As part of the larger Molecular Libraries Roadmap initiative, projects that are awarded under this FOA are subject to oversight and evaluation by each of the following entities.  Selection plan for assays to be implemented by the MLSCN will be developed and approved by the following committees based on scientific merit, NIH program priority and feasibility for HTS.

NIH PROJECT TEAM. The NIH Project Team will serve as the governing body that coordinates and oversees the interaction of NIH with the centers and the MLSCN Steering Committee.

MLSCN STEERING COMMITTEE. The steering committee for the overall MLSCN consists of the Director (PI) of each of the screening centers and the Small Molecule Repository, as well as NIH Program Managers and Science Officers, and will be the primary operational governing board of the MLSCN. The functions of this group include: 1) recommending the assignment and scheduling of assays and tasks, 2) developing guidelines to standardize the validation of screening data in different types of assays across centers; and 3) developing uniform procedures and policies for assay validation, data quality measures, assessment procedures, and annotation conventions for data depositions in PubChem.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity announcement (FOA) uses the NIH Small Research Grant (R03) award mechanism for biomedical researchers to obtain access to the MLSCN HTS and chemical optimization resources.  Investigators are expected to provide required reagents, travel to the screening centers and support development of chemical probes with secondary and counter-screening assays. Through its funding of the MLSCN, NIH will support the costs of assay automation, screening and optimization chemistry.

Competing renewal (formerly “competing continuation”) applications will not be accepted for the R03 grant mechanism. Small grant support may not be used for thesis or dissertation research. Up to two resubmissions (formerly “revisions/amendments") of a previously reviewed small grant application may be submitted. See NOT-OD-05-046, April 29, 2005.  Up to two resubmissions (formerly “revisions/amendments") of a previously reviewed small grant application may be submitted. See NOT-OD-05-046, April 29, 2005.

2. Funds Available

A project period of up to one year and a budget for total costs limited to $25,000 may be requested. Total costs include direct and facilities and administrative (F&A) costs. Budgeting travel for a brief visit to the collaborating center is recommended for setting up the primary and the secondary assays.  Equipment purchase is not an allowable cost.

The total number of R03s awarded will depend on the number of applications received, their relative scientific merit, and the general availability of funds for NIH Roadmap.

All awards are subject to the availability of funds. The estimated amount of funds available for support of projects awarded as a result of this announcement is $3,700,000 for fiscal year 2007.

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 institution 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.

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

Applicants may submit more than one application, provided each application is scientifically distinct. One application can contain parallel screens for multiple related molecular targets or cellular systems within a screening plan.

Section IV. Application and Submission Information


To download an 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:

PDs/PIs should work with their institutions/organizations to make sure they are registered in the NIH 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.

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 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.

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
R&R Budget Component
PHS398 Cover Page Supplement
PHS398 Research Plan
PHS398 Checklist

Optional Components:
PHS398 Cover Letter File
Research &Related Subaward Budget Form

Note: While both budget components are included in the SF424 (R&R) forms package, for this R03 use the detailed Research & Related Budget. Applications from foreign (non-U.S.) institutions submitted via Grants.gov using the SF 424 (R&R): Follow the Research & Related Budget Component Instructions. Complete and submit the RESEARCH & RELATED BUDGET forms. Do not complete or submit the PHS 398 Modular Budget component.

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/grants/policy/nihgps_2003/NIHGPS_Part12.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.

2.A. General Instructions

Follow the instructions for completing the SF424 components found in the Application Guide (http://grants.nih.gov/grants/funding/424/SF424_RR_Guide_General_Ver2.doc) with the following special instructions below.

2.B. SF424 (R&R) Cover Component

This is a required component for any SF424 R&R-based application package.

2.C. SF424 Research & Related Other Project Information

1. Are Human Subjects Involved? Check “no”.

2. Are Vertebrate Animals Used? Check “no”. (Check “yes” only when applicable such as Zebrafish based assay).

6. Project Summary/Abstract. The Project Summary/Abstract (i.e., “Description”) must state the application’s broad, long-term objectives and specific aims, making reference to the health relatedness of the project. Describe concisely the research design and methods for achieving the stated goals.

Attach Project Summary/ Abstract file in line 6, and the attachment must be a PDF format.

7. Project Narrative. Using no more than two or three sentences, describe the relevance of this project to public health or to one or more disease areas. Attach The Project Narrative file in PDF format in line 7.

A separate Research Plan component is required for NIH and other PHS agencies applications.

9. Facilities & Other Resources. Describe only those resources that are directly applicable to the proposed work. Provide any information describing the Other Resources available to the project and the extent to which they would be available to the project. This information is used to assess the capability of the organizational resources available to perform secondary assays, low-throughput screening of chemical analogs of hits developed by the MLSCN center, or chemical optimization efforts after the high throughput screening at the MLSCN. If appropriate, indicate previous interactions with screening centers in the MLSCN.

10. Equipment. Not applicable. Do not include an attachment here.

11. Other Attachments. If required, biosafety information for the biological material should be attached separately in line 11.

2.D. Senior/Key Person Profile(s) Component

Provide a biographical sketch for the Senior/Key Person. Recommended information includes: Education and Training, Research and Professional Experience, Collaborators and Affiliations (for conflicts of interest), Publications and Synergistic Activities. Save the information in a single PDF file and attach by clicking Add Attachment. Biographical sketches should follow the format described below.

NIH and Other PHS Agencies Instructions for a Biographical Sketch

Use the sample format on the Biographical Sketch Format Page http://grants.nih.gov/grants/funding/424/SF424R-R_biosketch.doc to prepare this section for all grant applications. Include biographical sketches for all Senior/Key Personnel. The Biographical Sketch may not exceed four pages per person. This 4-page limit includes the table at the top of the first page.

If the individual is registered in the eRA Commons, include the assigned Commons User Name in the “Credential” field. For principal investigators, this data item is required.

2.E. PHS398 Cover Page Supplement

2. Human Subjects. Check “no” to both the Clinical Trial and Agency-Defined Phase III Clinical Trial questions.

4. Human Embryonic Stem Cells. Check “no”. (Check “yes” only when applicable).

2.F. PHS398 Research Plan

Proposals for funding under this R03 mechanism are expected to include primary HTS assays, secondary assays and a plan for using identified active compounds in a follow-up research program. Although innovative proposals that are limited in scope will also be considered. 

Research plan must include the following information:

The following section contains the specific instructions for completing the research plan for these R03 applications. Page limitation for Research Plan: 10 pages single-spaced (excluding appendices). This form allows the attachment of the various sections of the standard research plan. This form collects each major section separately so that bookmarks and table-of-contents can be automatically generated for each section, by the NIH software that downloads, validates, and generates a grant image using the data received from Grants.gov. The PHS 398 Research Plan Component includes:     

2. Specific Aims: describe a rationale for the biological target or phenotype of the HTS and future plan for the use of the biological data or small molecule hits in a follow-up research program, either biological research or therapeutics development.

3. Background and Significance: describe the biological significance of the target or phenotype and potential impact of biological data and small molecule probes derived from the HTS assay on the scientific field of study.  If chemical probes already exist for the target protein, then justify the reason for generating more chemical probes,

4. Preliminary Studies: provide data and information on assay performance, quality controls, responses to pharmacological standards or other control conditions, feasibility for miniaturization and automation for HTS, tolerance to the effect of DMSO, reagent availability, reagent stability, etc.

5. Research Design & Methods:

Primary assay: Provide a detailed assay procedure for the primary assay, i.e. assay performed in a testing scheme to identify biologically active chemical entities in a screening mode. Include sources of specific materials such as purified or crude biochemical reagents or cells and the microtiter plate well density (e.g., 96-, 384- or 1536-well) and plate composition (e.g., clear bottom black or clear bottom polystyrene, etc.). Specify reagents, software, and instrumentation used to measure response or output. (e.g. Fluorescence polarization or Radiometric counting). The proposed assay should demonstrate highly robust and reproducible behavior in a 96-well or higher density format (e.g., 384- or 1536-well plates). Generally, the assay protocol should demonstrate: 1) a signal of sufficient intensity that it can be easily measured from a microtitre plate in low volume, 2) a signal-to-background ratio of at least 5 and a coefficient of variation (CV) below 10% determined from measurements across the entire plate (these factors are typically expressed as the statistical parameter, Z', which has an acceptable lower limit of 0.5), 3) reproducible, dose-dependent responses to pharmacological standards or other control conditions, 4) tolerance to the effect of DMSO at 0.1-1%. Between-plate and day-to-day variations also provide useful information on how well the assay will perform, as will the determination of reagent stability to storage and assay conditions. The assay plan should include demonstration of selectivity and reproducibility of response to a small but diverse collection of at least several hundred compounds, such as a collection of FDA approved drugs or other bioactive molecules.

Cost estimation: Estimate the costs of reagents that are commercially available. These costs should be calculated for a single well of a 96-well plate assuming an assay volume of 200 ul.

Secondary assays: Provide an available confirmatory assay that should use a different readout than the primary assay to confirm hits and eliminate false positives.  Provide a systematic process or a typical screening cascade to be used for evaluating the significance of active compounds identified in primary HTS, including descriptions of the secondary and counter-screening assays to assess selectivity or specificity. Selectivity assays are employed to elucidate the specificity of biologically active chemical entities towards a set of closely related targets. Counter-screening is to eliminate those active compounds that may also possess undesirable properties.

A plan to collaborate with the MLSCN center:  To increase the chance for  successful development of a chemical probe, a collaboration should be formed between the assay provider, MLSCN screening center, compound providers and NIH Science Officers. Describe an optimization plan that can benefit from the resources provided by the collaborators to advance hits to a chemical probe.  The submitting investigators are required to perform the following activities, including, but not limited to, facilitating the primary HTS, implementing secondary screens, and characterizing the final chemical probe(s) to explore physiological processes, cellular phenomena, and disease mechanisms in the context of biological research and therapeutics development.

17. Resource Sharing plan (s): Describe material(s) to be provided to screening center. Submitting investigators will be required to prepare and provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g. a known inhibitor of the target). Indicate if any reagents are proprietary and if so, if there are Material Transfer Agreements in place to use the proprietary reagents within the MLSCN if the assay is selected for implementation.

18. Appendix: up to two significant publications or achievements may be included in the appendix. (See NOT-OD-06-051)

2.G. PHS 398 Cover Letter File

PHS 398 Cover Letter File: Attach a letter agreeing to allow the R03 application to be shared with the MLSCN Steering Committee members for center assignment based on favorable review by the MLSCN Assay Access Committee. The letter should be brief and include the title of the application. The information in this application will be kept confidential.

The MLSCN Steering Committee, which consists of the Directors of the ten screening centers within the network, the Director of the Small Molecule Repository, and NIH staff, will develop a plan for distributing each HTS assay to a specific screening center based on existing capacity and expertise of each center as well as information such as assay target, cost, workload, detection system, etc. The MLSCN Steering Committee members will need to review the information in your application in order to make assay assignments to individual centers. No decision regarding the final assay assignment will be made without this letter of agreement.

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/grants/policy/nihgps_2003/NIHGPS_Part12.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.

3. Submission Dates and Times

See Section IV.3.A. for details.

3.A. Submission, Review, and Anticipated Start Dates
Opening Date: September 7, 2006 (Earliest date an application may be submitted to Grants.gov)
Letters of Intent Receipt Date
(s): Sept 26, 2006; Jan 26, 2007; May 26, 2007 and Sept 26, 2007
Application Submission
/Receipt Date(s): Oct 26, 2006; Feb 26, 2007; Jun 26, 2007 and Oct 26, 2007
Peer Review Date(s):
December 2006; April 2007; August 2007 and December 2007
Council Review Date(s):
May 2007; September 2007; January 2008 and May 2008
Earliest Anticipated Start Date
(s): June 2007; October 2007; February 2008 and June 2008

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 via email by the date listed in Section IV.3.A.

The letter of intent should be sent to:
Ingrid Li, Ph.D.
NIH Molecular Libraries & Imaging Roadmap.
National Institute of Mental Health/NIH/DHHS
6001 Executive Boulevard, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: ili1@mail.nih.gov

To permit expedited review of R03 applications, PD/PIs are asked to notify the NIMH Referral Office by email when the application has been submitted through Grants.gov.

NIMH Referral Office
Division of Extramural Activities
National Institute of Mental Health
6001 Executive Boulevard, Room 6154, MSC 9609
Bethesda, MD 20892-9609
Telephone: (301) 443-3367
FAX: (301) 443-4720

Email: NIMHReferral@mail.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 electronicallyPAPER APPLICATIONS WILL NOT BE ACCEPTED.

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 FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application.

Note:  Since email can be unreliable, it is the responsibility of the applicant to check periodically on their application status in the Commons.

The NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial merit review unless the applicant withdraws the pending application. The NIH will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of an application already reviewed with substantial changes, but such application must include an “Introduction” addressing the previous critique. Note such an application is considered a "resubmission" for the SF424 (R&R).

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

6. Other Submission Requirements

Cover Letter to allow reviewing of R03 application with the MLSCN Steering Committee: The NIH requires the PD/PI to submit a letter with their application, agreeing to allow their application to be shared with the MLSCN Steering Committee members. The information in their applications will be kept confidential. This letter should be appended to Optional Components: PHS398 Cover Letter File in the application package.

Preliminary data, particularly for primary assays, are required for R03 applications in response to this FOA: This NIH R03 small grant is to support discrete, well-defined assay projects that realistically can be screened by the MLSCN centers and that require limited levels of funding.  Because the Research Plan component is restricted to 10 pages, the PI/PDs should put emphasis on methodological details and certain indicators used in evaluating the performance of the assays including supportive preliminary data. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or from investigator-generated data. For R03 applications in response to this FOA, preliminary data are required, particularly for primary assays.

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.”

Renewal (formerly “competing continuation” or “Type 2”) applications are not permitted.

All application instructions outlined in the SF424 (R&R) Application Guide are to be followed, with the following requirements for R03 applications:

Warning: Please be sure that you observe the total costs, project period, and page number limitations specified above for this FOA. Application processing may be delayed or the application may be rejected if it does not comply with these requirements.

Note: 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.  

Plan for Sharing Research Data

All applicants must include a plan for sharing research data in their application. 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. The funding organization will be responsible for monitoring the data sharing policy. The presence of a data sharing plan will be part of the terms and conditions of the award. Program staff of the funding organization and NIH Project Team staff will be responsible for monitoring the data sharing policy. For the MLSCN Project Team Policy on Data Sharing and IP in the MLSCN Program, see http://www.nimh.nih.gov/dnbbs/datasharing-ip.pdf.

Sharing Research Resources

NIH policy requires that grant awardee 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/grants/policy/nihgps_2003/NIHGPS_Part7.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.

Guidance for Community Resources. The following data and materials generated or developed through the ML Roadmap initiative are expected to be community resources: (1) primary data from HTS and from secondary screens; (2) protocols for assays implemented in the MLSCN; (3) the chemical structures of compounds tested in the MLSCN; and (4) the optimization chemistry protocols for probe development conducted within the MLSCN centers. In keeping with this approach, NIH expects that (1) all assays and assay protocols submitted to the NIH under this FOA, and (2) biological screening data derived from implementing the assays in the MLSCN will be made readily available and accessible, consistent with other facets of the ML Roadmap http://grants.nih.gov/grants/guide/notice-files/NOT-RM-04-014.html

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization and by NIH Project Team staff when making recommendations about selecting assays for implementation within the MLSCN.

Submitting investigators will be required to provide necessary reagents such as cells expressing recombinant enzymes/proteins, primary and secondary antibodies, tagged peptide substrates, and available positive controls (e.g. a known inhibitor of the target).

Submitting investigators and MLSCN Centers will be expected to use an unmodified version of the Material Transfer Agreement (MTA) approved by the MLSCN Steering Committee for transfer of assays and materials to the individual MLSCN Centers.

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 will be evaluated for scientific and technical merit by an appropriate review group convened by NIMH accordance with the review criteria stated below.
 
As part of the initial merit review, all applications will:

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 comments, 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. The scientific review group will address and consider each of these criteria in assigning the application's 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 practice be advanced? Is this assay for a novel biological target or cellular process? Is there no known small molecule modulator for this biological target available? Is there a need for better small molecule modulators against the target? Is this class of target extensively investigated? Is there an adequate plan for evaluating the activities of the compounds identified in a high throughput screen, e.g., in secondary screens and functional assays? Are there important and well-defined goals for the use of small molecule compounds identified with the proposed assay, either as research tools or for therapeutics development?

Approach. Is the assay well established and ready for HTS? Is the assay pharmacologically validated? Is there sufficient preliminary data for assay validation? Is there an assay performance parameter calculated, such as Z-factor? Is the assay readily adaptable by screening centers to an HTS format that is primarily characterized by miniaturization and automation? Is the assay feasible and reproducible, and does it and meet minimum statistical thresholds for robotic screening? Is there an adequate plan for assay reagents? Are the assay reagents readily available from the applicant (s) if reagents can not be commercially supplied? Is there an adequate plan for secondary assays to evaluate active compounds identified in the primary assays?

Innovation. Is the assay development project original and innovative? For example: Does the assay challenge existing paradigms or practice; address an innovative hypothesis or barrier to progress in the field of HTS? Does the project develop or employ novel concepts, approaches, methodologies, tools, or technologies for this area?

Investigators. Are the investigators appropriately trained and sufficiently knowledgeable about the target and area of science to support the collaborative screening effort and capable of advancing active compounds identified by the MLSCN? Are the investigators reasonably knowledgeable and experienced about assay development and the process of screening compounds library?

Environment. Does the scientific environment of the applicant (s) 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 item 6 of the 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 five items described under item 11 of the Research Plan component of the SF424 (R&R) will be assessed.

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.  

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the data sharing plan or the rationale for not sharing research data may 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 funding organization will be responsible for monitoring the data sharing policy. The presence of a data sharing plan will be part of the terms and conditions of the award. Program staff of the funding organization and NIH Project Team staff will be responsible for monitoring the data sharing policy. http://grants.nih.gov/grants/policy/data_sharing

2.D. Sharing Research Resources

NIH policy requires that grant awardee 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/grants/policy/nihgps_2003/NIHGPS_Part7.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 will be considered by Program staff of the funding organization when making recommendations about funding applications. Program staff may negotiate modifications of the data and resource sharing plans with the awardee before recommending funding of an application. The final version of the data and resource sharing plans negotiated by both will become a condition of the award of the grant.

Submitting investigators will be required to indicate whether or not they have Material Transfer Agreements or Sponsored Research Agreements in place to use patented technology or assay reagents proposed in this application for non-commercial, research purposes. Investigators will be asked to provide documentation prior to assay being selected for implementation within the MLSCN.

3. Anticipated Announcement and Award Dates
N/A

Selection of assays for the MLSCN: The following is the anticipated process for assay selection following peer review:

Peer review results will be communicated to the NIH MLSCN Project Team and to the MLSCN Steering Committee.

NIH MLSCN Project Team: Summary statements will be assessed and prioritization of applications will be developed that is consistent with the review results and NIH-wide programmatic priorities. The list of recommended assay applications will be presented to the MLSCN Steering Committee for implementation within the screening centers network. The recommendations of the MLSCN Steering Committee regarding the choice and distribution of assays to specific centers will be reviewed and final assignments of these assays to specific centers will be made.  The Project Team gives final approval for assay assignments to individual centers.

MLSCN Steering Committee: HTS assay applications are selected by NIH project team and a plan for distribution of assays to specific centers within the screening centers network are developed.  The plan is based on the NIH Project Team's prioritization of assays that have fared well in peer review and are acceptable for implementation.  Information is also considered regarding existing capacity and expertise of each center such as assay target, cost, workload, detection system, etc.

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/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.

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:

Ingrid Li, Ph.D.
NIH Molecular Libraries & Imaging Roadmap.
National Institute of Mental Health
6001 Executive Blvd, Room 7185, MSC 9641
Bethesda, MD 20892-9641
Telephone: (301) 443-5288
FAX: (301) 402-4740
Email: ili1@mail.nih.gov

Christine Colvis, Ph.D.
NIH Molecular Libraries & Imaging Roadmap.
National Institute on Drug Abuse
6001 Executive Blvd, Room 4282, MSC 9555
Bethesda, MD 20892-9555
Telephone: (301) 435-1323
Email: ccolvis@nida.nih.gov

2. Peer Review Contacts:

Yong Yao, Ph.D.
Scientific Review Branch
National Institute of Mental Health
6001 Executive Blvd, Room 6149, MSC 9608
Bethesda, MD 20892-9608
Rockville, MD 20852 (for overnight couriers)
Telephone: 301.443.6102
FAX: (301) 402-0182
Email: yyao@mail.nih.gov

3. Financial or Grants Management Contacts:

Dawn E.  Walker
Grants Management Branch
National Institute of Mental Health
6001 Executive Blvd, Room 6118, MSC 9605
Bethesda, MD  20892-9605
Rockville, MD 20852 (Express Mail)
Telephone: 301-443-3858
Fax: 301-443-6885
Email: WalkerDE2@mail.nih.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 (45CFR46) 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).

Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

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 (HHS) 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 HHS 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) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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 PA 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 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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