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 a Common Fund initiative (http://commonfund.nih.gov/ ) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/).  The FOA will be administered by the National Institute on Deafness and Other Communication Disorders (NIDCD), (http://www.nidcd.nih.gov/) on behalf of the NIH.

Title: Production Of Human Proteins To Be Used For Generating Affinity Reagents (U01)

Announcement Type

New

Request For Applications (RFA) Number: RFA-RM-10-007

Catalog of Federal Domestic Assistance Number(s)
93.310

Key Dates
Release Date: February 26, 2010
Letters of Intent Receipt Date(s): March 26, 2010
Application Receipt Dates(s): April 26, 2010 
Peer Review Date(s): June-July, 2010
Council Review Date(s): August, 2010 
Earliest Anticipated Start Date: September 30, 2010
Expiration Date: April 27, 2010

Additional Overview Content

Executive Summary

• Purpose. This FOA is the first component of a pilot program organized under the NIH Common Fund Protein Capture Initiative to examine the feasibility and value of generating a community resource of high quality, renewable affinity reagents for all human proteins. This specific FOA topic is focused on the production of proteins or peptides for the purpose of generating monoclonal antibodies that can be used in immunoprecipitation studies, and potentially for other affinity reagents, as well as broader uses by the scientific community and others. Thus, the FOA solicits projects that will provide the targeted proteins, peptides or other immunogens to other components of the pilot program (including a component that will generate monoclonal antibodies, to be solicited in FY2011), as well as to the wider community in the form of a renewable resource, e.g., clones or transfected cell lines.  This FOA will prioritize human transcription factors as an initial set of targets. 
• Mechanism of Support. This FOA will utilize the U01 Research Project Cooperative Agreement activity code.
• Funds Available and Anticipated Number of Awards..We expect to fund a single three year award in FY2010. Total funds available for the program are $1M, for each of three years.   .
• Budget and Project Period.  Applications should propose no more than $600,000 in direct costs per year over a period of no more than three years.
• Application Research Strategy Length: The U01 Research Strategy section may not exceed 12 pages, including tables, graphs, figures, diagrams, and charts.  See Table of Page Limits.
• Eligible Institutions/Organizations. Institutions/organizations listed in Section III, 1.A. are eligible to apply.
• Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals with the skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their institution/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.
• Number of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.
• Number of Applications. An individual PI may submit only one application.
• Resubmissions.  Resubmission applications are not permitted in response to this FOA. 
• Renewals. Renewal applications are not permitted in response to this FOA. 
• Special Date(s). This FOA uses non-standard due dates.
• Application Materials. See Section IV.1 for application materials.
  Hearing Impaired.  Telecommunications for the hearing impaired are available at: TTY: (301) 451-5936

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(s) 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. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
    A. Receipt, Review and Anticipated Start Dates
         1. Letter of Intent
    B. Sending an Application to the NIH
    C. Application Processing
   D.  Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements

Section V. Application Review Information
1. Criteria
2. Review and Selection Process
3. Anticipated Announcement and Award Dates

Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
     A. Cooperative Agreement Terms and Conditions of Award
         1. Principal Investigator Rights and Responsibilities
         2. NIH Responsibilities
         3. Collaborative Responsibilities
         4. Dispute Resolution Process
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 initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Purpose and Context.  The scope of this FOA is limited to the production of a specific subset of human proteins to be used in the generation of a specific class of affinity reagents.  However, it is important to understand that the FOA is the initial component of a pilot project designed to evaluate the feasibility and value of a larger integrated effort, the NIH Common Fund Protein Capture Initiative, to produce a comprehensive set of widely usable, renewable, affinity reagents for the human proteome.

The pilot project is intended to address several issues that must be addressed before the comprehensive Protein Capture Initiative can be considered.  During the pilot phase, (1) the ability of the most mature technology available, monoclonal antibody production, to scale to the level needed for generating antibodies against all human proteins will be tested, and (2) approaches to large-scale generation of other types of affinity reagents will be examined.  Specifically, the goals of the pilot project are to:

1) Within a three-year span, begin to generate a monoclonal antibody affinity resource for human proteins, starting with the comprehensive set of human transcription factors. Monoclonal antibody technology is given priority because it is a mature technology and produces a renewable source of affinity reagents.   Transcription factors were chosen as an initial target sub-proteome set because the lack of affinity reagents for this set of proteins presents an immediate bottleneck for high-throughput studies of genome function, including those being carried out under the ENCODE program (see http://www.genome.gov/10005107). Finally, the initial priority is for affinity reagents that can be used in chromatin-immunoprecipitation studies (ChIP), but in the long term we intend that the affinity reagents produced in the Common Fund Initiative should be useful for a broad range of applications.

2) Assess whether monoclonal antibody technology is practically amenable to being scaled up to produce a comprehensive renewable affinity resource for the entire human proteome. The assessment will need to include understanding issues of target representation, quality, utility for multiple end uses, throughput, and cost.

3) Investigate and stimulate alternative approaches that offer significant improvements over monoclonal antibody technology that may become mature in the next three to five years, and assess their capabilities, including quality, scalability, renewability, and multiplicity of end uses against the mature technologies.

As already noted, in FY 2011 NIH intends to release FOAs for additional components of the pilot effort, including one to solicit one or more projects to produce cost-effectively high-quality monoclonal antibodies to human transcription factors usable in immunoprecipitation studies, and one to investigate and stimulate alternate technologies and methods for other types of affinity reagents.   

The NIH Common Fund Protein Capture Initiative. Broadly defined, affinity reagents are very widely used by the biological and biomedical research and clinical communities. Even confining the discussion to antibodies and their derived reagents, there are many applications as research tools, for example to purify, quantitate, and characterize proteins (e.g., immunoaffinity purification, ELISA, Western Blot), and to understand protein function and associations (e.g., immunohistochemistry, immunoprecipitation, mass spectrometry assays), among others.  Clinical uses of affinity reagents include biomarker assays, and (more recently) as pharmaceutical and targeted therapeutic agents. A variety of affinity reagents have been developed.  Many are antibody-based such as monoclonal/polyclonal antibodies, antibody fragments, single chain antibodies, and recombinant antibodies.   There are also a number of alternative, non-antibody-based approaches for generating affinity reagents, including, affibodies, aptamers, and small molecules, although these are currently less well developed with regard to comprehensiveness, production, and a broad range of end uses.

There are already very many sources of protein affinity reagents, both publicly and privately funded, too many to summarize. However, with some notable exceptions (e.g., polyclonal antibodies to produce an atlas of protein localization- http://www.hupo.org/research/hai/ and http://www.proteinatlas.org/), these efforts are not presently focused on, or moving towards, providing a comprehensive, renewable, consistent, well-characterized human protein-affinity reagent resource for broad use by the scientific community. The purpose of the NIH Common Fund Protein Capture Initiative is to explore how to implement such a resource, given the considerable utility it would have for biomedical research, including high-throughput proteomic studies, and for advancing human health.

Achieving such a comprehensive resource involves addressing many challenges, including its potentially open-ended nature, depending on how the human proteome is defined; the many technologies that must be considered; and the many end-uses for affinity reagents.  Thus, development of the project and assessment of its feasibility must be carefully staged and prioritized. It is for this reason that the pilot project has been designed to focus on monoclonal antibodies as a mature technology for producing a renewable resource on the set of human transcription factors as initial targets, and on immunoprecipitation—especially for chromatin-IP applications—as an end-use.

Specific Objectives of this FOA. It is important to stress that this FOA, RFA-RM-10-007, is focused on only a single, initial, component of the pilot program: the production and provision of a set of human proteins (transcription factors) and/or appropriate derivatives, to be used in the generation of a set of monoclonal anti-transcription factor antibodies that can be used in immunoprecipitation studies.  The priority of the pilot project is on generation of monoclonal antibodies that can be successfully used in immunoprecipitation studies.  This end use may dictate the properties of the antibodies produced (such as high selectivity for a single transcription factor, high affinity for the transcription factor, and other properties) which may, in turn, dictate the properties of the immunogens produced.  The application should present a strategy for producing useful quantities of each human transcription factor or a derivative of each in a form that would be effective for use in generating monoclonal antibodies useful for immunoprecipitation, and the rationale for choice of the strategy.  More than one protein or derivative per transcription factor is allowable, and the application should discuss the relative merits of the protein product(s) produced for achieving the goal of generating at least one useful monoclonal antibody per transcription factor.  The applicant should discuss all issues related to high-throughput protein production, including cost, quality assessment and quality control, rate of production, and any other issue that the applicant deems relevant. The research plan should present and justify any further prioritization within this project, beyond those of the focus on human transcription factors, monoclonal antibodies, and immunoprecipitation as an end-use.

While the focus of this FOA is on the generation of proteinaceous immunogens for the generation of anti-human transcription factor monoclonal antibodies, it is important to stress that this is a component of a pilot project that, if successful will scale to produce a comprehensive resource. In estimating the funding for this FOA, NIH made certain assumptions about the costs of producing immunogens for the set of human transcription factors. However, we explicitly encourage applicants to propose cost-efficient approaches that would allow the stated minimum research objectives to be exceeded by reducing overall cost, allowing the investigator to go beyond producing the immunogens that represent the set of human transcription factors, to those that represent larger proportions of the human proteome.  In any event, proposals should be based on a strategy that can eventually scale to a level that will support the generation of such antibodies or other affinity reagents for use with a much larger set of human proteins, specifically at least one protein or derivative representing each protein-coding sequence in the human genome, and with broad utility beyond immunoprecipitation.  The application should, therefore, address the generalizability of the proposed strategy, if appropriate by including plans for obtaining information about approach, coverage, quality, cost, and scalability.

It is anticipated that the product of the proposed work (e.g. purified proteins or peptides) will be provided to the other NIH project components  (described above) of this pilot program, beginning within 6-12 months of the funding of this FOA, towards an effort to produce monoclonal antibodies to all known human transcription factors. The research plan should, therefore, include a plan for providing the products to an antibody-generation effort and a timetable that will result in the first set of transcription factor-based products being provided on this schedule, i.e. by April 1, 2011.  The research plan should also describe how coordination with an antibody-generation effort could be achieved.

It is also anticipated that all of the renewable products that result from work funded under this FOA will be provided to the broader scientific community. Depending on the approach, these may include clones or transfected/transformed bacterial or other cell lines.  The application should, therefore, also include a plan for making such products available generally.

Types of research and experimental approaches. This FOA does not limit the approaches that may be proposed, as long as they address the Research Objectives. Strategies for generating proteins of optimal utility (short peptides, protein domains, full length proteins, etc.), cell types used (bacterial, fungal, etc.) and other significant components of the research plan should be clearly stated and rationalized in terms of the research objectives. 

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 will use the U01 Research Project Cooperative Agreement activity code.
The Project Director/Principal Investigator (PD/PI) will be solely responsible for planning, directing, and executing the proposed project.  

This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award".

2. Funds Available

Approximately $1M total funds will be available for this FOA for each of three years. Support may be requested for no than $600,000 in direct costs per year. NIH anticipates making only one award.

Although the financial plans of the IC(s) provide support for this program, awards pursuant to this funding opportunity are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications.

Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.

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

Section III. Eligibility Information

1. Eligible Applicants

1.A. Eligible Institutions

The following organizations/institutions are eligible to apply:

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education
• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education) Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Small Businesses
• For-Profit Organizations (Other than Small Businesses)
• State Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribally Designated Organizations
• U.S. Territory or Possession
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Organizations)
• Other(s): 
  • Eligible Agencies of the Federal Government

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the 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 program support.  In addition, investigators from the NIH Intramural Research Program are eligible to participate in this FOA.  Applications from intramural investigators will be competitively reviewed.

More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, 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 grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. 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 PDs/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

Number of Applications. An individual PI may not submit more than one application.

Resubmissions.  Resubmission applications are not permitted in response to this FOA. 

Renewals. Renewal applications are not permitted in response to this FOA. 

Section IV. Application and Submission Information

1. Address to Request Application Information

The current PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. 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 PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).

Applications must have a D&B Data Universal Numbering System (DUNS) number as the universal identifier when applying for Federal grants or cooperative agreements. The D&B number can be obtained by calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should be entered on line 11 of the face page of the PHS 398 form.

The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.

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:

• Request budgets in U.S. dollars.
• Contain detailed budgets. See NOT-OD-06-096.

In addition, for applications from foreign organizations:

• Charge back of customs and import fees is not allowed.
• Every effort should be made to comply with the format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF.
• Funds for up to 8% Facilities and Administrative (F&A) costs (excluding equipment) may be requested. See NOT-OD-01-028, March 29, 2001.                        
• Organizations must comply with Federal/NIH policies on human subjects, animals, and biohazards.
• Organizations must comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., “Administrative and National Policy Requirements”

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.

Applications with Multiple PDs/PIs 

When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.

All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.

Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled “Multiple PD/PI Leadership Plan” 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, and should include 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.

Additional information is available in the PHS 398 grant application instructions.

SPECIAL INSTRUCTIONS  

Applications Involving the NIH Intramural Research Program

The requests by NIH intramural scientists will be limited to the incremental costs required for participation.  As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs).  These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses.  Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits. 

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

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

3. Submission Dates and Times

Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date: March 26, 2010
Application Receipt Date: April 26, 2010
Peer Review Date(s): June – July, 2010
Council Review Date: August, 2010
Earliest Anticipated Start Date: September 30, 2010

3.A.1. Letter of Intent

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

• Descriptive title of proposed research
• Name, address, and telephone number of the Principal Investigator
• Names of other key personnel
• Participating institutions
• Number and title of this funding opportunity

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:

Nancy L. Freeman, Ph.D.
Division of Scientific Programs
National Institute on Deafness and Other Communication Disorders
National Institutes of Health Executive Plaza South-400C 6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Tel: (301) 402-3458
Fax: (301) 402-6251
Email: FreemanN@mail.NIH.gov

3.B. Sending an Application to the NIH

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

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

Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).

3.C. Application Processing

Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed.  Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.

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 as an investigator-initiated application, is to be submitted in response to a 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.

Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.

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. The Grants Policy Statement can be found at 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: 1) are necessary to conduct the project, and 2) 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 NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)

6. Other Submission Requirements

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".

Management plan. In addition to the overall research plan, the application must include a specific plan about how the work will be managed to ensure production of proteins according to the stated, well-justified timeline. This plan should also consider the need to interact with other, future components of the pilot program discussed herein. Budgets and justification should clearly account for costs related to management, including collaboration costs (meetings). This should be one page and should follow the research plan.

Reagent distribution plan. Distribution of proteins and clones (or other renewable component) is a critical and integral part of the requested research effort. Applicants should include one page detailing plans and a budget for distribution of the proteins or peptides produced to the antibody-generating component of the pilot project, as well as distribution of the renewable resources generated under the award to the broader scientific community. Where possible, distribution should occur from multiple sites, such as for the distribution of the clones from the Mammalian Gene Collection (MGC); see http://mgc.nci.nih.gov/.  The distribution plan should follow the research plan. It is assumed that provision of resources to other components of this pilot project will be integral to the research plan. Applicants should acknowledge NIH policies on research tools http://ott.od.nih.gov/policy/research_tool.html. See also Resource Sharing Plans below.

NIH policy calls for grant recipients to make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible. Notwithstanding this general policy, investigators should propose a plan to share the immunogens produced with the other components of this initiative as each is produced, according to a schedule to be determined by the Steering Committee and Project Team (see section VI below). 

The adequacy of the resources sharing plan 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 routine progress reports generated under the Cooperative Agreement terms (See Section VI). 

PHS398 Research Plan

All application instructions outlined in the PHS 398 Application Instructions are to be followed, with the following additional requirements:

• Introduction (required for a resubmission or revision application) is limited to 1 page.
• Specific Aims is limited to 1 page.
• Research Strategy, including tables, graphs, figures, diagrams, and charts is limited to 12 pages. See Table of Page Limits.

Budget Component

This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). 

Appendix Materials

All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.

Do not use the Appendix to circumvent the page limitations.  An application that does not observe the required page limitations may be delayed in the review process.

Resource Sharing Plan(s)

NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(a) Data Sharing Plan: Regardless of the amount requested, investigators are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.

(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible.  A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition.  For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Specific Instructions for Foreign Applications

All foreign applicants must complete and submit budget requests using the PHS 398 Detailed Budget pages. See NOT-OD-06-096.

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

Review 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 the Center for Scientific Review and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As part of the scientific peer review, all applications will:

• Undergo a selection process in which only those applications deemed to have the highest scientific and technical merit, generally the top half of applications under review, will be discussed and assigned an impact/priority score.
• Receive a written critique.
• Receive a second level of review by the appropriate national advisory council or board.

The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability.  As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system. 

Overall Impact

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

Scored Review Criteria

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

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

Investigator(s).  Are the PD/PIs, collaborators, and other researchers well suited to the project?  If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training?  If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)?  If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Innovation.  Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions?  Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense?  Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Approach.  Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project?  Are potential problems, alternative strategies, and benchmarks for success presented?   If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?

Does the research plan clearly describe the appropriateness of the proteins/peptides that will be produced for generating monoclonal antibodies that will be useful for immunoprecipitation applications (e.g., ChIP)? Does the justification for each component of the process (choice of antigen, cell type that will be used to produce it, etc.) adequately consider issues of the properties and quality (e.g., specificity, affinity, utility) of the monoclonal antibodies or other affinity reagents that will be generated against it? Is the plan cost-efficient? Does it aim to realize improved cost efficiencies during the term of the award? Does the approach adequately address the ultimate need for comprehensive coverage of all human transcription factors? Does the proposed approach have promise for scaling up to ~20,000 or more unique human proteins?  In addition to, or beyond, addressing the priorities stated in the “Research Objectives” section above, is the research plan likely to produce reagents that have the broadest possible utility?  

Environment.  Will the scientific environment in which the work will be done contribute to the probability of success?  Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed?  Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? 

Additional Review Criteria

As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.

Protections for Human Subjects.  For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects  and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.

Inclusion of Women, Minorities, and Children.  When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.

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

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

Additional Review Considerations

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

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

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

Resource Sharing Plans.  Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable:  1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).

Budget and Period Support.  Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Selection Process

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by peer review
• Availability of funds
• Relevance of the proposed project to program priorities
• A resource distribution plan that is consistent with the specific goals of this program to provide immunogens to the antibody-production component of the Protein Capture Initiative pilot project, as well as to generate a resource for the scientific community.

NIH will consider the following in evaluating applications for cooperative agreements submitted in response to this FOA:

• The scientific and technical merit of the proposed program;
• The qualifications and experience of the project director and other key personnel;
• The statutory and program purposes to be accomplished;
• The extent to which the funded project would be coordinated with the other components of the pilot project. 
• The extent to which the funded project can be coordinated with similar efforts by other organizations
• The management plan and the administrative and managerial capability of the applicant; and
• Other factors which the awarding IC considers appropriate in light of its particular statutory mission.

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 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 Also 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 (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

2. A.1. Principal Investigator Rights and Responsibilities

The Principal Investigator (PI) will coordinate project activities scientifically and administratively at the awardee institution.  The PI will have primary responsibility for defining the details for the projects within the guidelines of this FOA, and for performing all scientific activities.  The PI will agree to accept the close coordination, cooperation, and participation of the NIH staff in those aspects of scientific and technical management of the project as described below.

Specifically, the PI of this protein production center will:

1.         Determine experimental approaches, design protocols, set project milestones, conduct experiments, and analyze and interpret research data.  Provide protein products for use by the antibody-generating component of the Protein Capture Initiative pilot project on the schedule proposed in the research proposal, or on another schedule as agreed to by the Steering Committee and Project Team.

2.         Provide goals for implementation, throughput, quality, and cost to the NIH Program Official and Project Scientist as requested (usually at the outset of the award and in quarterly progress reports, but also at other times as requested by the Program Official and Project Scientist)

3.         Participate, along with critical staff, in project Steering Committee meetings held once annually in the metropolitan Washington, DC or other area.

4.         Adhere to policies regarding data release, data standardization, standardization of experimental protocols, and other policies that might be established, as agreed upon by the Steering Committee and the Project Team.

5.         Ensure that any renewable (e.g., clone-based) protein reagents developed, experimental protocols, and critical data about the reagents will be made available to the scientific community according to the manner and timeline agreed upon by the Steering Committee and the Project Team. The Steering Committee and Project Team recommendation will be consistent with the ongoing genomic research tool sharing policies of the NIH. Share reagents, tools, and data of interest with other components of the Protein Capture pilot project and collaborators as agreed upon by the Steering Committee and Project Team.

6.         Accept and implement all scientific, practical, and policy decisions approved by the Steering Committee and the Project Team.

7.         Submit data and/or protein reagents for quality assessment in any manner specified by the Steering Committee, Project Team, or External Scientific Panel (ESP; see below).

8.         Agree not to disclose confidential information obtained from other members of the research network.

10.        Be prepared for annual administrative site visits by NIH staff.

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

2. A.2. NIH Responsibilities

An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.

Project Scientist Responsibilities:  The Protein Capture Initiative Project Scientists are NIH extramural program scientists who will have substantial scientific involvement during the conduct of this activity, through technical assistance, advice, and coordination above and beyond normal program stewardship for grants. This includes facilitating the partnership relationship between NIH and the entity funded under this RFA, and with members of any future components of the Protein Capture program, helping to maintain the overall scientific balance in the program commensurate with new research and emerging research opportunities, and ensuring that the activities of the project is consistent with the mission of the Protein Capture Initiative program. However, the role of the Project Scientist will be to facilitate and not to direct. The funded project will have one designated Project Scientist.

The Project Scientist will have the following substantial involvement:

1.     Provide ongoing coordination and tracking of the activities of the grantee.

2.     Provide relevant scientific expertise and overall knowledge.

3.     Assist in the integration of the individual awardees from this and future components of the Protein Capture program into a research network, including coordinating regular conference calls for sharing of approaches and fostering collaborations.

4.     Assist in efforts for data and experimental protocol standardization efforts.

5.     Participate, as a voting member, with the other Steering Committee members in the group process of setting research priorities and milestones, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it.

6.     Develop, with input from the Steering Committee and the Project Team, progress report formats (quarterly and annually) for all grantees.

7.     Provide relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions to serve on the External Scientific Panel.

8.     Participate in the External Scientific Panel (ESP) meetings.

9.     Serve as scientific liaison between the awardee, other NIH program staff, and the Project Team.

10.   Report periodically (e.g., monthly) on the progress of the Protein Capture Initiative program to the Project Team.

11.   Assist in developing timelines for the wide distribution of data, experimental protocols and software tools to the scientific community, in accordance with the decisions of the Steering Committee and Project Team.

12.   Assist in avoiding unwarranted duplication of effort across the program, and help coordinate collaborative research efforts that involve multiple grantees in the Protein Capture Initiative program components.

13.   Review and comment on critical stages of program development for presentation to the Project Team and External Scientific Panel before subsequent stages are implemented.

14.   Retain the option to recommend, with the advice of the External Scientific Panel, additional research endeavors within the constraints of the approved research and negotiated budget to the Project Team.

15.   Retain the option to recommend, with the advice of the External Scientific Panel, re-allocation of NIH support among awardees within the overall Protein Capture Initiative program, as scientific goals evolve.  To  help carry out these duties, Project Scientists may consult with non-NIH experts in the field.

Project Team Responsibilities:  The Project Team will serve as the trans-NIH body overseeing and coordinating the activities of all program components. Project Team membership will include one or more representative(s) from each of the NIH Institutes and Centers (IC) participating in the program. Program Officials and Project Scientists can be members of the Project Team. Each participating NIH IC will have a single vote on the Project Team, no matter how many members from the NIH IC are involved. The Project Team will receive recommendations from the Steering Committee and will be overseen by the Project Team co-chairs.

The Project Team will have the following involvement:

1.     Review and implement guidelines and policies based on recommendations from the Steering Committee.

2.     Communicate, through its chair, policy information to the Steering Committee, other components and the co-chairs.

3.     Monitor the progress of all program activities to determine the appropriateness of the use/continued use of project resources.

4.     Evaluate progress of the program in consultation with the ESP.

Attend the ESP meetings and other program meetings.

Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

2.A.3. Collaborative Responsibilities

Steering Committee Functions. The Steering Committee is the operational group responsible for coordination of the activities of all components of the Protein Capture Initiative program. The Steering Committee will identify scientific and policy issues that need to be addressed by all components of the program, develop recommendations to the Project Team for addressing such issues, coordinate the primary recommendations for choice of experimental protocol, help prioritize the protein targets for the program, and coordinate the dissemination of data, assay protocols, reagents, and other materials with the wider scientific community.

The Steering Committee membership will include the PI of each of the awards made within the program, and the Project Scientists.

The PI of each center (or designee) will have one vote on the Steering Committee. The Project Scientists may vote, but the total votes will count as a maximum of one-third of the total Steering Committee votes. Membership on the Steering Committee becomes effective upon issuance of the Notice of Award. It is anticipated that additional coordination mechanisms will be set up with other U.S. and international groups that may join this effort. The Steering Committee may add additional members. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. The Steering Committee may establish additional subcommittees or workgroups for specific tasks. No NIH staff member may chair any committee or subcommittee.

The Steering Committee will:

1.     Convene at least once per year. The purpose of these meetings is to assess scientific progress, identify new research opportunities, establish priorities, consider policy recommendations, and discuss strategies. One of the meetings will be in conjunction with the annual meeting of the ESP.

2.     Make decisions by a majority vote of a quorum, with an attempt for a consensus. A quorum will be the presence of a majority of the center PIs or their designees, and at least one Project Scientist. Outside consultants/experts may be asked to participate in these discussions as nonvoting advisors.

3.     Establish a chair, or workgroups for specific tasks; the Project Scientists may not chair any committee or workgroup.

4.     Hold conference calls of the full committee and any workgroups as needed; monthly calls are anticipated.

5.     Develop recommendations for guidelines and policies for prioritizing development of reagents (antigens or antibodies), quality control and quality assurance of reagents and annotation of reagents, and other standards that are needed for, e.g., consistency across all program components and/or utility of the regents to the community.

6.     Help develop any non-standard report formats, for example reports pertaining to production goals, and to determine their frequency.

7.     Develop policies to facilitate the timely and reasonable availability of program resources/reagents.

8.     Serve as a venue for coordination on improving the state-of-the-art for all program activities by reporting progress, disseminating best practices, and collectively evaluating new procedures, resources, and technologies.

9.     Identify opportunities to increase the interoperability of all relevant components within the program; grantees will be expected to have a high degree of flexibility and be willing to adopt uniform policies and procedures recommended by the Steering Committee and approved for implementation by the Project Team.

10.   Develop recommendations for guidelines for publication of results, and global data analyses, etc. resulting from the program.

11.   Address recommendations made by the External Scientific Panel and approved for implementation by the Project Team.

External Scientific Panel (ESP):  The ESP will be responsible for reviewing and evaluating the progress of the Protein Capture Initiative program in meeting their individual and collective milestones and goals, and making recommendations about the progress and directions of the program and individual components to the Project Team. The ESP will be composed of 3-6 senior non-federal scientists who are not directly involved in the activities of the program. The Project Team will appoint members to the ESP. The Project Team will select one member as chair. The Project Scientists, and Project Team members may attend the External Scientific Panel meetings as non-voting participants.

The ESP will have the following involvement:

1.     The chair will schedule, develop agendas, and oversee the annual meetings and conference calls. The membership of the Panel may be enlarged permanently, or on an ad hoc basis by action of the original members.

2.     The ESP will review progress of the program and individual components, and make recommendations regarding any changes that may be needed in the direction of the program to the Project Team.

3.     The ESP will be consulted by the Project Scientists and Project Team when changes in an award’s funding level are being considered because of either outstanding or poor technical performance, or for other reasons.

4.     Any component PI who considers a Steering Committee decision unacceptable may appeal to the ESP.

ESP members will be invited to attend as observers at the annual meetings of the Steering Committee.

Each full member will have one vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

2.A.4. Dispute Resolution Process

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

3. Reporting

Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

Awardees may also be required to submit specific progress reports on, for example, reagent production progress, as determined by the Steering Committee.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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:

Nancy L. Freeman, Ph.D.
Division of Scientific Programs
National Institute on Deafness and Other Communication Disorders
National Institutes of Health Executive Plaza South-400C
6120 Executive Blvd. MSC-7180
Bethesda, MD 20892-7180
Tel: (301) 402-3458
Fax: (301) 402-6251
Email: FreemanN@mail.NIH.gov

2. Peer Review Contacts:

Richard Panniers, Ph.D.
NIH/CSR
Center for Scientific Review, Room 2198
6701 Rockledge Dr. Bethesda, MD 20892
Email: PANNIERR@csr.nih.gov
Tel: 301-435-1741
Fax: 301 480 2067

3. Financial or Grants Management Contacts:

Mr. Christopher Myers
Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders
6120 Executive Blvd., EPS 400B, MSC-7180
Bethesda, MD 20892-7180
Email: myersc@nidcd.nih.gov
Tel: (301) 435-0713
Fax: (301)402-1758

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.

Policy for Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/

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 http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, 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.

Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.

All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

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-09-116.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.

NIH Public Access Policy Requirement:
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award.  For more information, see the Public Access webpage at http://publicaccess.nih.gov/.

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) 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 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. 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 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 NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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.