Participating Organization(s)	National Institutes of Health (NIH)
Components of Participating Organizations	This Funding Opportunity Announcement (FOA) is developed as a Common Fund Initiative (http://commonfund.nih.gov/ ) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Human Genome Research Institute (NHGRI/NIH), (http://genome.gov) on behalf of the NIH.
Funding Opportunity Title	Production of Affinity Reagents for Human Transcription Factors (U54)
Activity Code	U54 Specialized Center- Cooperative Agreement
Announcement Type	New
Related Notices	December 3, 2010 - Notice of Pre-application Teleconference for Request for Applications. See Notice NOT-RM-11-003.
Funding Opportunity Announcement (FOA) Number	RFA-RM-10-017
Companion FOA	RFA-RM-10-018
Number of Applications	Only one application per institution is allowed Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)	93.310
FOA Purpose	This NIH Common Fund FOA seeks to establish a center or centers to produce renewable, high quality affinity reagents against all human transcription factors. The resulting set of affinity binding reagents is intended to form a broadly available community resource for researchers with an interest in transcription factors. This FOA requests applications that will develop an affinity reagent resource of the broadest possible utility, including detection of the target protein in a sample, immuno-histochemical labeling of a tissue sample, or immunoprecipitation or other affinity capture of the target protein. However, the scientific application that is the highest priority for this FOA is the use of the reagents in chromatin immunoprecipitation (ChIP) studies. It is anticipated that awarded applications will propose to create production centers capable of implementing a pipeline that would include acquisition and evaluation of human transcription factor immunogens, production and selection of affinity binding reagents, and the adequate biochemical characterization and validation of the affinity reagents. Because this FOA will support a production activity, it is anticipated that the center(s) will emphasize the advantages of high throughput and scalability to be achieved within a production effort, and will for example develop process improvements, thereby improving cost and quality over the duration of the award. At the same time, the production center must maintain a degree of scientific flexibility for example to develop approaches to producing affinity reagents to less tractable transcription factor protein targets as they are identified in the course of production. Finally, because this FOA is intended to fund a broadly available community resource of research tools, applicants are expected to propose a viable distribution plan that is consistent with NIH policies, described below, and ensures broad availability and wide accessibility for future use of the reagents with minimal constraints, consistent with achieving the goals of this funding initiative.

Posted Date	December 3, 2010
Open Date (Earliest Submission Date)	Not Applicable
Letter of Intent Due Date	January 4, 2011
Application Due Date(s)	Standard dates February 4, 2011.
AIDS Application Due Date(s)	Not applicable
Scientific Merit Review	Standard dates July, 2011
Advisory Council Review	Standard dates August, 2011
Earliest Start Date(s)	Standard dates September, 2011
Expiration Date	February 5, 2011
Due Dates for E.O. 12372	Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 Application Guide except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. While some links are provided, applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

Nature of Research Opportunity. This NIH Common Fund FOA seeks to establish a center or centers that can produce renewable, high quality affinity reagents against all human transcription factors. The resulting set of reagents is intended to form a broadly available community resource for researchers with an interest in transcription factors.

This FOA requests proposals that will develop an affinity reagent resource for human transcription factors of the broadest possible utility, including possible detection of the target protein in a sample, immuno-chemical labeling of a tissue sample or cells, or immunoprecipitation of the target protein. However, the scientific application that is the highest priority for this FOA is the use of the reagents in chromatin immunoprecipitation studies (ChIP).

It is anticipated that awarded applications will propose to create production centers capable of implementing a pipeline that would include acquisition and evaluation of human transcription factor immunogens, determination, production and selection of affinity binding reagents, and the adequate biochemical characterization of human transcription factor binding reagents. Because this FOA will support a production activity, it is anticipated that the center(s) will emphasize the advantages of high throughput and scalability to be achieved within a production effort, and develop process improvements to improve costs and quality over the duration of the award. At the same time, the production center must maintain a degree of scientific flexibility, to develop approaches to producing affinity reagents to less tractable transcription factor protein targets as they are identified in the course of production.

NIH recognizes there are alternative approaches to affinity reagent production. We encourage applications that propose creative or newer approaches that increase throughput, quality, and utility to the community, and reduce cost, as long as they do so within the context of a production pipeline that will produce a broadly available community resource consisting of high quality affinity reagents to all human transcription factors by the end of the funding period. That is, the proposed approaches must be convincingly scalable at the present time, and applications must propose a well-justified production plan that can begin upon funding and within the given FOA budget.

Finally, because this FOA is intended to fund a broadly available community resource of research tools, applicants are expected to propose a viable distribution plan that is consistent with NIH policies, described below, and ensures broad availability and wide accessibility for future use of the reagents with minimal constraints, consistent with achieving the goals of this funding initiative.

Background. Affinity reagents are broadly and extensively used by the biomedical research community in a multitude of applications such as the detection of targets and associated proteins by affinity capture or immunoprecipitation, determination of cellular localization, and detection of the a protein in a sample. Beyond widespread uses in research, affinity reagents can be used in diagnostic assays, and more recently have been developed as pharmaceutical agents. A discussion at a recent NIH workshop on production of affinity reagents estimated that the market for just research antibodies is in excess of $500M/year (http://commonfund.nih.gov/proteincapture). Market research summary information available on the Internet gives a significantly larger estimate of $2B/year in 2009 (http://www.biocompare.com/Documents/surveys_files/ExecSumm/Antibodies_2009_ExecSumm.pdf ).

Traditionally, investigators developed affinity reagents to proteins of direct interest to their studies. Increasingly, it has become possible to purchase affinity reagents (either monoclonal or polyclonal antibodies), and while there are many available, they are often limited to well-studied protein targets (for which there is a known demand). Investigators who wish to study proteins that have not already been well characterized are consequently left without commercial reagents. Further, NIH has been advised that the quality of the commercial affinity reagents that are available is not consistently reliable, especially for different applications, often resulting in wasted experiments and false experimental leads. The high demand, concerns about quality, and the desirability of an unbiased approach that is not being taken by the private sector, are reasons to contemplate a publicly funded effort. More recently, a substantial public effort was funded to produce a comprehensive set of polyclonal antibodies to human proteins (http://www.proteinatlas.org) made available through a private vendor. There are also other public efforts, of more focused scope, to develop and distribute antibodies of interest to specific research communities (see http://antibodies.cancer.gov/).

Because of the clear demand for such a resource, NIH, through the Common Fund (http://commonfund.nih.gov/), has initiated a production effort for protein affinity reagents with the present focus on human transcription factors. This effort is intended to complement existing sources of affinity reagents in a number of respects:

• The resource should be broadly available and comprehensive in the long term. Current research affinity reagents are available only for a relatively small number of well-studied proteins. The lack of availability of an unbiased set of such reagents limits what can be studied;
• There is a need for a resource of uniformly high quality affinity reagents, with detailed information about their characterization;
• The resource should be broadly available and readily distributable to and useable by the community. For example, the reagents should be renewable, useful for many applications, and their use should not be unduly constrained by high cost or inappropriate intellectual property constraints;
• Taken together, these three points are consistent with a production effort, in which it is more possible to produce a resource with uniform high quality and that is comprehensive in its outlook, where there is a possibility of reducing the cost of production over time, and where terms of distribution are not fragmented among many different reagent collections;
• The recent workshop (http://commonfund.nih.gov/proteincapture) identified at least two different approaches to generating affinity reagents that could be implemented as production efforts: monoclonal antibodies, and recombinant antibodies selected through immunoglobulin display. This provided confidence that scalable production approaches sought by this FOA are now available. It is important to note that this FOA does not prescribe any specific technical approach (see below).

The long term goal of this NIH program is to develop a broadly available and comprehensive affinity reagent resource for the entire human proteome, useful for as many research applications as possible. However, the focus of this FOA is on a subset of human proteins. This focus was chosen for several reasons. First, the current cost of developing affinity regents is high, which forces some prioritization. An initial focus on a limited set of proteins will demonstrate the ability to produce high-quality renewable reagents at scale, and explore the potential for improvements (cost, quality, utility, etc.) in the long term. NIH believes that this knowledge is essential to provide the basis for designing, and justifying, a long-term, more comprehensive project. The focus on the ~1500 human transcription factors was chosen for several reasons. There are clearly other sub-proteomes that would be of high biological interest and the current choice of transcription factors for the purposes of developing a pipeline is somewhat arbitrary. However, this class of proteins is of clear interest for understanding fundamental aspects of gene regulation. In addition, this set of targets has immediate relevance for participants in the ENCODE consortium (http://www.genome.gov/10005107), who represent a population of likely early users of the resource. Finally, we are not aware of other public efforts with a specific interest in this class of proteins.

NIH also understands that affinity reagents can be developed for different end uses and applications. With this FOA, NIH seeks reagents that can be used for multiple applications, but the highest priority for this class of protein targets is for use in chromatin immunoprecipitation experiments.

Beginning a production effort now does have certain disadvantages--one of them is that it may inhibit exploration of alternative approaches that could be better (for example with regard to cost, quality, or utility) if they were given the chance to demonstrate some potential to scale. Moreover, any single production approach is likely to be sub-optimal for some very interesting classes of target, or for some particular end-use. To partially address this concern, and to increase the chances that the long-term goals of the overall program can be achieved, NIH will release another FOA (see RFA-RM-10-018) to fund the further development of alternative approaches.

NIH considers this program, taken as a whole, to be a pilot that will inform the long-term objective of developing affinity reagents against the entire human proteome, while in the next five years (or less) providing high-quality reagents against an important sub-proteome, the transcription factors. Because of the risk entailed in a pilot effort, NIH will issue any awards under this FOA as a Cooperative Agreement, and will evaluate the funded award(s) in an ongoing way, with an assessment of the awards in the context of the program as a whole to take place in the third year of funding to determine the level of success of the effort and to inform funding of the remainder of the award.

Scientific Knowledge to be Achieved. With this FOA, NIH intends to establish a center(s) that:

• Identifies, prioritizes, and acquires all required transcription factor immunogens, in collaboration with other components of the program; (http://commonfund.nih.gov/proteincapture/fundedresearch.asp);
• Develops a state-of-the-art pipeline for the production of protein affinity reagents, with the aim of producing binding reagents against all human transcription factors;
• Has the ability to make continuing gains in efficiency and quality through incremental improvements in production and through scale;
• Is able to carry out both initial characterization and validation;
• Has the ability to collaborate productively with other significant public efforts to create affinity reagent resources for the community;
• Will make the reagents and information about the reagents known to the community, and collaborate effectively with private and non-profit groups that can distribute the reagents to the community;
• Has an effective center management structure.

Each of these will be discussed in detail below.

Identification, prioritization, and acquisition of immunogens. The NIH Common Fund Protein Capture program has already funded an effort (http://commonfund.nih.gov/proteincapture/) to provide immunogens for the Protein Capture program, including the center(s) funded under this FOA. Developing a supply of immunogens ahead of the development of an affinity reagent production pipeline has advantages, but will require additional coordination once the research under this FOA has begun.

Prioritization. We anticipate that the production component, funded by this FOA, will use immunogens produced by and initially prioritized by the immunogen development effort (http://commonfund.nih.gov/proteincapture/fundedresearch.asp). Once an affinity reagent production group is funded, additional immunogen prioritization and assessment will be a joint program responsibility. Applicants need not specify transcription factor priorities in their application. They should, however, discuss practical issues that could affect prioritization, including the effect of budget considerations on number and scope of targets, or technical limitations of the proposed approach that bear on the prioritization scheme (for example, if the classes of protein are more easily targeted by the proposed approach).

Acquisition. The applicant should include plans for acquisition of human transcription factor immunogens. Although we have assumed that the immunogen production effort already funded will supply immunogens for the production effort, we appreciate that there may need to be some flexibility. For example, it is possible that the program may need to modify (within reason) the immunogen development effort to accommodate the affinity reagent production approach. It is also possible that the program will identify other sources of immunogens that will provide an advantage (for example, there may be some developed by other public efforts). Finally, it is possible that the funded approach for production of affinity reagents will not require immunogens in the usual sense. In that case, the immunogens will represent a list of priorities and potentially a set of validation targets; there must be thought given to the final priority of use in ChIP applications if considering alternative immunogen sources.

Applicants should discuss how their proposed approach will interface with the immunogen production effort, including how the immunogens will be brought into the pipeline and/or their use as potential validation targets. Applicants should more generally discuss procedures for introducing immunogens into their pipeline, for example requirements for immunogens to be useful in their pipeline, description of routine quality checks, etc.

Production pipeline. The applicant should provide plans for how he or she will develop a highly efficient, scalable production pipeline for affinity reagents against human transcription factors, justifying the technical approach, and also should describe how an efficient pipeline will be established using that approach.

Technical approach. The applicant should describe past relevant results and plans for the basic technical approach to making and selecting affinity reagents (e.g., monoclonal antibodies, recombinant antibodies, aptamers, etc.). This approach should be justified in terms of all the purposes of this FOA, for example: ability to be used in a high-throughput production pipeline; ability to scale; cost; technical and practical ability to obtain reagents against all, or as many as possible, of the human transcription factors; utility for the likely end-uses or applications (including ChIP applications); advantages compared to comparable approaches; usability by the community (including advantages for distribution, availability of secondary reagents, ability to label the reagents for various applications, etc.).

Applicants should include other important information relating to the goal of successfully generating a useful resource--for example, with the proposed approach, how many affinity reagents should be generated per immunogen target in order to optimize utility to the community? NIH has been advised that a minimum of two reagents per target should be sought; however applicants should propose and justify a number balancing quality, scientific utility, and costs.

Pipeline development. The applicant should describe past experience pertaining to, and plans for, developing an integrated and efficient production pipeline for affinity reagents. The applicant should discuss and justify all major components of the pipeline. The applicant should identify the critical factors in establishing such a pipeline and discuss how those will contribute to the production effort. Applicants should identify factors that that are likely to limit throughput, quality, or that are cost-drivers.

The applicant should discuss how production will be assessed, what criteria will be applied to determining success at various stages, and also how the process will be monitored to identify any problems within the pipeline. Applicants should discuss routine pipeline quality control, for example quality control for routine chemical or other reagents to be used in the process. Applicants should discuss how standard operating procedures will be developed. Applicants should discuss any laboratory information management systems or other informatics that will support their effort.

Applicants should discuss and justify any automation that they will use in terms of how it will improve efficiency, cost, quality, or other aspects of production.

The applicant should discuss current and expected costs per reagent and per target for the initial year of the award, and to discuss plans for reducing costs. Applicants should clearly state what is included, and not included, in cost estimates for producing reagents.

Applicants should discuss personnel, including center leadership, staffing and training relevant to the production pipeline.

Applicants should provide timelines and relevant milestones for all critical aspects of pipeline development and production goals including quality goals.

Notes on Utility: In their justifications for the approach, production pipeline and for characterization and validation (below), applicants should keep in mind that the affinity reagents developed against human transcription factors solicited under this program are intended to have multiple uses, including detection of the presence of a protein in a sample (e.g., enzyme-linked immunoassay, Western blot), identifying or tagging cells expressing the protein, or for determining tissue or sub-cellular localization (e.g. flow cytometry, immunohistochemistry, immunoflourescence), and for capturing target and associated proteins (e.g. immunoprecipitation). Some classes of affinity reagents have additional uses (e.g., intrabodies for probing function). For the purposes of this program, NIH encourages the production of reagents that will be useful for any (or as many as possible) of these applications. However, the highest priority application for this program is the ability to use the reagents in ChIP experiments, consistent with the interest in developing resources for transcription factors. A separate aspect of utility that should be addressed is the ability for end users to adopt the reagents to their assays, for example with detection by appropriate secondary reagents.

Continuing improvements. The applicant should include a discussion of plans for improving the production pipeline within the given FOA budget. Plans for routine improvements in cost or quality should be discussed, for example, by identifying and addressing important cost-drivers, by modifying protocols or methods, by cost advantages of scale, etc.

Initial Characterization and Validation. The applicant should discuss and justify plans for initial characterization and validation, and how this will be integrated into the production effort. NIH has been advised that initial characterization of the specificity and affinity (association and dissociation constants) is very important. Additional characterization, for example epitope mapping, may also be valuable. Applicants should propose and justify initial characterization for reagents, including stating criteria for success, based on the importance for assuring a high-quality resource of affinity reagents against human transcription factors.

Applicants must propose and justify appropriate validations for reagents, and discuss how validation will be integrated into the production process. Validations should be adequate to maximize the likelihood that the reagent will be of high quality for the end-uses discussed here (see "Notes on Utility", above), especially ChIP applications. In other affinity reagent generation programs, validations include immunoflourescence, immunohistochemistry, Western blot, and immunoprecipitation.

NIH is aware that the costs of characterization and validation can be high. For example, in some respects, the best validation for these reagents could be performing a ChIP-sequence experiment, costing in the range of $8000 each. This would be prohibitive. NIH encourages approaches that have the potential to reduce validation cost, balanced against quality, for example through efficiencies of scale, through creative staging or early elimination of reagents that are likely to fail subsequent steps, or by finding proxies for more extensive validation.

Validation and characterization data, along with accompanying protocols, is to be considered part of the "output" of the center, along with the reagents themselves. Any reagent distributed will be accompanied by these data.

Ability to collaborate productively with other significant public efforts. NIH acknowledges other international efforts to develop protein capture reagents for the human proteome. NIH believes there are a number of opportunities for collaboration of potentially high mutual benefit towards developing a comprehensive resource. The applicant should very briefly discuss any past or present collaborations in this field, along with ideas for points of future collaboration.

Resource Sharing: Informing the community about the resource, and providing for distribution. The applicant should propose a basic mechanism to make the list of reagents and characterization/validation information broadly available. Within this FOA, we do not envisage an elaborate implementation of a Web portal for this resource. As the program develops, NIH intends to explore appropriate mechanisms to make a more developed vehicle to disseminate information about the resource, possibly in collaboration with other significant affinity reagent development efforts.

The applicant should discuss plans for reagent distribution. As one of the essential goals of this program, NIH intends that the reagents be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling creative scientists to perform experiments and encouraging creative downstream applications for the reagents. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov). In order to ensure that the further development of these reagents is not unduly impaired or impeded, applicants are expected to submit a sharing plan that addresses how they will meet the goals of this funding initiative.

In order to realize their different advantages for reagent distribution, NIH has been advised to seek parallel distribution mechanisms, both non-profit (to ensure the availability of the basic resource), and for-profit (which could add further value to commonly used reagents). Applicants may, but are not required to, identify specific distributors. However, they should discuss how their distribution plans are consistent with both mechanisms. See Research Plan Guidance, below. Final distribution plans are subject to approval by NIH program staff.

NIH understands that the specifics of distribution may depend on the nature of the reagent (for example, recombinant antibodies can be distributed as clones). Applicants should point out any inherent advantages that their approach may have for distribution.

Plans for informing the community and resource distribution should be included in a separate Resource Distribution plan section of the application. See "Other information about application content and form" below.

An effective center management structure. The applicant should include an overall management plan for the center in a separate section of the application. See Section IV: Reseach Plan below for details.

The NIH encourages all proposed programs to foster the participation of individuals from racial and ethnic groups underrepresented in biomedical and behavioral research, individuals from disadvantaged backgrounds, and individuals with disabilities.

See Section IV.2 Content and Form of Application Submission for specific information about page lengths and application organization.

Funding Instrument	Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.
Application Types Allowed	New The OER Glossary and the PHS398 Application Guide provide details on these application types.
Funds Available and Anticipated Number of Awards	NIH Common Fund will commit at least $4M/year for five years; one or two awards are anticipated in FY2011. Although the financial plans of the NIH provides 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.
Award Budget	Individual application budgets should not exceed $2.6M per year, direct costs and must reflect actual needs of proposed project.
Award Project Period	The total award period requested for this FOA may not exceed five years

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

Higher Education Institutions:

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

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

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

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

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

Non-domestic (non-US) entities (Foreign Organizations)

Foreign (non-U.S.) components of U.S. Organizations are allowed.

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

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

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the PHS398 Application Guide.

The lead Principal Investigator must devote at least 3 person/months and effort to this Cooperative Agreement.

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

Only one application per institution (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

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

It is critical that applicants follow the instructions in the PHS398 Application Guide, except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

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

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

The letter of intent should be sent to:

Adam L. Felsenfeld, Ph.D.
Program Director, Large-Scale Sequencing
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892
Telephone: 301-496-7531
Email: adam_felsenfeld@nih.gov

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and 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)

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

• Applications in response to this FOA should include three Research Plan sections: I. Center Research strategy (30 pages); II. Resource Distribution plan (no more than 6 pages); III. Overall Management plan (no more than 6 pages). Details are provided in the Research Plan section below.

Resource Sharing Plan

Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS) as provided in the PHS398 Application Guide.

Appendix

Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide,

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

I. The Center Research Strategy (30 pages maximum) should include a description of relevant past work (preliminary results) and a research plan for all aspects of the center described in the section above entitled "Scientific Knowledge to be Achieved" with the exception of the Resource Distribution Plan and the Management Plan.

II. The application is expected to contain a separate Resource Distribution plan (6 pages maximum) consistent with the discussion above in the section "Scientific Knowledge to be Achieved". 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.

Applicants are expected to include discussion of:

• Availability of the reagents;
• Availability of information about the reagents (validation, characterization data); this may require a basic implementation of a Web portal. Alternately, if there is a community database suitable for these data, the applicant should identify it and provide data;
• Availability of protocols for validations/characterization;
• Availability of any software tools developed for this award using NIH funds.

In addition to the considerations stated above in "Scientific Knowledge to be Achieved", NIH notes that there are some challenges in distributing affinity resources. First, this is to some extent dependant on the nature of the reagents. For example, the developmental studies hybridoma bank (http://dshb.biology.uiowa.edu/) is a publicly-funded distributor that would be suitable for approaches that involve hybridomas, but other mechanisms maybe more appropriate for, e.g., recombinant approaches that use clones as an intermediate. Second, although NIH has been advised to take advantages of the strengths of both the public sector and the private sector in distributing this resource, NIH cannot in advance specify a specific private partner or partners for this effort. Ideally, it will be possible for a number of entities to distribute these reagents.

Potential sites and web portals that the applicants can consider for distribution include, but should not be limited to, the Proteome Binder consortia (http://www.proteomebinders.org/), the University of Iowa hybridoma bank (http://dshb.biology.uiowa.edu/), The Protein Atlas (http://www.proteinatlas.org). The applicant can also consider the development of an independent site, but interaction with other ongoing efforts in the community is strongly encouraged for maximizing the potential impact of the present effort in the scientific community. Finally, applicants should also consider the possibility of depositing resources into a centralized repository that may be established or otherwise designated in the future for this funding initiative by the NIH to maximize availability and accessibility of these resources and furthering research, consistent with achieving the goals of this project.

Resource distribution plans should include discussion of how any intellectual property will be managed. It is intended that the tools of scientific discovery necessary to rapidly and effectively develop new diagnostics, therapeutics and other medical applications be widely available for research use. Accordingly, awardees will be expected to manage intellectual property in a way that is consistent with achieving the goals of the program and in accordance with applicable NIH guidelines and best practices. Resource distribution plans should assure that licensing and sharing practices ensure the availability of data and research resources for future use by the scientific community, and that research collaboration or sponsorship agreements are consistent with the requirements of the Protein Capture program and meeting its programmatic goals.

Restrictive licensing and sharing practices for this program could substantially diminish the value and public benefit provided by this community resource project. Management practices that would prevent or block access to, or use of, these resources for research use will be considered to be hindering the goals of the program. Applicants are encouraged to clearly demonstrate in their Resource Distribution plan how their strategies will achieve the desired public benefit and programmatic goals through effective sharing of resources generated under this award.

The adequacy of the Resource Distribution plan will be considered in the review, with respect to how readily the reagents can be distributed, how consistent the plans are with the ability to broadly distribute through multiple mechanisms, and the plans for providing access to the validation and characterization data that will accompany the reagents.

The adequacy of the Resource Distribution plans, with regard to their overall consistency with the intention to create a broadly available and readily distributable public resource, will be assessed by Program staff when making recommendations about funding applications. The effectiveness of the resource distribution plan will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm).

Specific Resource Distribution plans, once approved, will also become Terms and Conditions of award.

III. The application must contain a separate Management Plan (maximum 6 pages).

Applicants must describe the organizational infrastructure to support and coordinate project administration within the proposed center.

In this section, applicants must address the following elements:

• A description of the project leadership and key personnel, and their responsibilities. The PI is expected to devote 3 person/months) to this award. While it is up to the applicant to provide a specific management structure, this FOA calls for a complex multi-component production effort, which will require dedicated specialized key personnel with appropriate levels of expertise and responsibility overseeing critical aspects of the production effort. It is expected that these individuals will need to dedicate a significant amount of effort in day-to-day management of the center. For example, the PI may designate someone in the role of a scientific project manager to oversee daily operations. Alternately (or in addition) the PI may choose dedicated experienced individuals to lead critical components of their pipeline. Such individuals are expected to have appropriate expertise in addition to scientific expertise, including knowledge of and experience in project management, ability to use project management tools, leadership skills, ability to maintain and communicate appropriate records, and ability to collaborate with all components of the proposed effort. The management leadership structure, and individuals identified to fulfill those roles, should be justified based on their appropriateness to the proposed effort.
  
  
• A description of how the various components of the center will be managed in an integrated way. This includes a description of how communications will be handled within the center, lines of authority, and how decisions will be made. It is critical to describe how any components that are at another physical site will be managed and integrated (e.g. subcontracts).
  
  
• It is highly likely that the formation of project sub-committees or working groups will be recommended by the steering committee to resolve program-wide issues (e.g., quality, validation, exchange of immunogens/reagents, distribution). Applicant Management Plans should anticipate the need for this level of collaborative activity among the program Research Network components.
  
  
• The management plan should include its own budget request and justification, including funds for coordination among components and travel (including travel for key personnel to Steering Committee meetings; see below).

In addition to the instructions above regarding the three Research Plan sections, the application should include the following.

• A one-page statement of specific aims.

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants administration.

This initiative is not subject to intergovernmental review.

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

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Significance

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

Is there a high likelihood that the proposed center can produce high-quality affinity reagents to human transcription factors, based on the applicant’s past experience and the proposed future plans? Is there a high likelihood that the applicants can accomplish this at levels of throughput, data quality, and cost within the scope and award period anticipated by this FOA?

Is there a likelihood that the activities of the proposed center will provide useful information about how to pursue a larger-scale effort, for example by providing insight into bottlenecks, cost-drivers, and other significant aspects of scale?

Is there a high likelihood that the affinity reagents will be of high utility to the community, considering all relevant factors such as quality, ability to be used in a range of applications-- most importantly ChIP--readiness for use by a range of researchers (for example, ease of labeling, existence of secondary reagents)?

Is there a high likelihood that the center will make significant contributions to the state-of-the-art in the production of affinity reagents?

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 applicant have adequate plans for increasing throughput while lowering costs? Does the applicant have a successful record in this regard?

Is there adequate description of acquisition and coordination of immunogens from the currently funded immunogen production effort? If alternatives are proposed, are they likely to be an advantage in the ultimate production of affinity reagents?

Does the applicant have adequate plans for incremental development related to large-sale generation of affinity reagents, identifying and solving critical integration problems, and adopting solutions to increase efficiency and lower costs? Does the applicant have a successful record in this regard?

Does the applicant have adequate plans for bioinformatics infrastructure/laboratory information management? Does the applicant have a successful record in this regard?

Are the resource distribution plans adequate with respect to how readily the reagents can be distributed consistent with achieving the program goals? Are they consistent with the ability to distribute through multiple mechanisms? Are the plans adequate for providing access to the validation and characterization data that will accompany the reagents? Is there evidence that the systems are in place to support resource distribution?

Is there an adequate management plan appropriate to the scope of the proposed work? Will the various components---including subcontracts--proposed be well-integrated?

Does the applicant have a successful record of collaboration in this field?

Environment

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

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact/priority score, but will not give separate scores for these items.

Protections for Human Subjects

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

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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

Biohazards

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

Resubmissions

Not applicable

Renewals

Not applicable

Revisions

Not Applicable

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

Resource Distribution Plan

Reviewers should consider and comment on, but not score, the aspects of the Resource Distribution plan that pertain to overall consistency of the plans with the intention to create a readily distributable public resource, including licensing and intellectual property issues that need to be consistent with the goals of this FOA for a broadly available resource that is readily usable by the community, as outlined above.

Applications from Foreign Organizations

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

Select Agent Research

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

Resource Sharing Plans

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) Convened by The Center for Scientific Review. (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

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 overall impact/priority score.
• Receive a written critique.

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• The overall consistency of the Resource Distribution Plan with the intentions of this program to create a broadly available community resource, as detailed above.
• The ability of awardees to collaborate where necessary, on large projects of critical strategic importance to the NIH, for example, the ENCODE project.

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.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to the DUNS, CCR Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the N0A. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. . More information is provided at Award Conditions and Information for NIH Grants.

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

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

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

• Defining the details for the center within the guidelines of this RFA and for performing the scientific activities. The P.I. will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."

The P.I. of a center will:

• Determine experimental approaches, design protocols, set project milestones and conduct experiments;
• Provide goals for throughput, quality, and cost to the NIH as requested (usually at the outset of the award and annually thereafter, but also at other times as requested by NIH program staff);
• Ensure that the affinity reagents meets the quality standards and costs agreed upon at the time of award or any improved quality standards and costs negotiated during the award period;
• Ensure that resources developed as part of this project, and accompanying characterization/validation data, are made broadly available according to NIH policies, and in a manner to be approved by NIH staff, and that results are published in a timely manner, consistent with achieving the goals of this program funding;
• Adhere to the policies regarding intellectual property and other policies that might be established during the course of this activity;
• Integrate with the program's process for selecting targets (immunogens), and to make best-faith efforts to develop affinity regents to those targets as negotiated with program staff;
• Submit data for assessment in any manner specified by the Steering Committee or the External Scientific Consultants (ESC) to the program;
• Submit progress reports as agreed upon by the Steering Committee and the ESC;
• Accept and implement any other common guidelines and procedures developed for the NIH Protein Capture and approved by the Steering Committee and the ESC;
• Accept and participate in the cooperative nature of the Protein Capture research network;
• Coordinate and collaborate with other U.S. and international groups engaged in similar large affinity reagent generation projects;
• Inform the NIH Program Director of all major interactions of members of the Steering Committee;
• Attend Steering Committee meetings.
• 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 DHHS, PHS, and NIH policies and meeting the goals of this funding initiative.

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

• During the conduct of this activity provide technical assistance, advice and coordination. However, the role of NIH will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the Protein Capture research network and that NIH staff will be given the opportunity to offer input to this process;
• NIH Project Scientists shall participate in the Steering Committee and will collectively have one vote.
• The Project Scientist will:
• Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it;
• Negotiate throughput, quality, cost goals, and affinity reagent target (immunogen) prioritization with the awardees as necessary;
• Serve as a liaison between the awardees and the ESC, the Protein Capture Working Group co-chairs, the NIH Common Fund, the appropriate Advisory Councils, and the larger scientific community;
• Coordinate the efforts of the awardee with others engaged in similar efforts, including other awardees under this program and those awardees involved in related NIH programs, and with the international community involved in creating a public resource of affinity reagents;
• Attend all Steering Committee meetings as a (single) voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Lend relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve on the ESC and the Steering Committee; serve as liaison between the Steering Committee and the ESC;
• Serve on subcommittees of the Steering Committee and the ESC, as appropriate;
• Provide advice in the management and technical performance of the investigation;
• Assist in promoting the broad availability of the resources developed in the course of this project to the scientific community at large;
• Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend, with the advice of the ESC, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award;
• Additionally, an agency program official or IC Program Director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director will coordinate with the NIH Project Scientist, and will attend Steering Committee and ESC meetings.
  
  An agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

• Participate in the Steering Committee. A Steering Committee will serve as the main governing board of the Protein Capture program. The Steering Committee membership will include the Project Scientist(s) and the P.I. of each awarded cooperative agreement, for all (Affinity Reagent Production, Immunogen Production, and Technology Development) components of the Protein Capture research network. The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. At the discretion of NIH staff, in consultation with the Steering Committee and the ESC, sub-committees of the Steering Committee may be created in order to focus on topics that are of specific interest to either Production or Technology Development activities, for example in cases where program decisions will substantially affect one activity but not the other. All Steering Committee decisions are subject to final approval by the NIH.

The Steering Committee will:

• Discuss progress in meeting the goals of various sequencing projects;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for reagent quality measures, validation and assessment, conventions for reagent distribution, or measuring costs and throughput. Adoption of procedures and policies developed by the Steering Committee will require concurrence by the ESC;
• Serve as a venue for coordination on the improvement of the development of affinity reagents, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies;
• Schedule the time for, and prepare concise (3 to 4 pages) summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting;
• Each full member (limited to one person per awarded center, in the case of multiple PI’s per center) will have one vote except NIH Project Scientist(s), who will have one collective vote. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee;
• Steering Committee meetings will take place by telephone or in person, with at least one in-person meeting per year (see below) and other meetings to be determined by NIH staff in consultation with the Steering Committee. It is highly likely that project sub-committees or working groups will be recommended by the steering committee to resolve program-wide issues (e.g., quality, validation, exchange of immunogens/reagents, distribution);
• Another area of joint responsibility is that NIH and the grantees will work with and provide information to a group of External Scientific Consultants (ESC);
• The ESC will be responsible for reviewing and evaluating the progress of the members of the Research Network toward meeting their individual and collective goals. The ESC will provide recommendations to the Protein Capture Common Fund Working Group, the Directors of NHGRI, NIDCD, NIGMS, and DPCPSI as well as the Directors of all other participating NIH Institutes and Centers about continued support of the components of the Research Network. The Research Network will receive a critical evaluation in the third year of the award specifically to evaluate the interim success of the program. The ESC is composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the Protein Capture Research Network. The membership of the ESC may be enlarged permanently, or on an ad hoc basis, as needed;
• The ESC will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the ESC members to interact directly with the awardees. Annually, the ESC will make recommendations regarding progress of the Research Network and present advice about changes, if any, which may be necessary in the Protein Capture program to the Protein Capture Common Fund Working Group, the Directors of NHGRI, NIDCD, NIGMS, and DPCPSI as well as the Directors of all other participating NIH Institutes and Centers.
• The Working Group consists of program staff from each of the NIH Institutes and Centers supporting the Protein Capture Research Network. The purpose of the Protein Capture Working Group will be to disseminate information about the progress of the Protein Capture Research Network to the participating Institutes and Centers and to provide a forum for the Working Group to discuss issues related to the Protein Capture Research Network.

Dispute Resolution:

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

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

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

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.FSRS.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936
Email: GrantsInfo@nih.gov

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939
Email: commons@od.nih.gov

Adam L. Felsenfeld, Ph.D.
National Human Genome Research Institute()
Telephone: 301-496-7531
Email:adam_felsenfeld@nih.gov

Joseph D. Mosca, Ph.D., M.B.A.
Center for Scientific Review
National Institutes of Health
Phone: 301 408-9465
E-mail: moscajos@csr.nih.gov).

Cheryl Chick
Grants Management Branch()
Telephone: 301- 496-7531
Email: chickc@mail.nih.gov

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

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