National Institutes of Health (NIH)
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
Funding Opportunity Title
Production of Affinity Reagents for Human Transcription Factors (U54)
Funding Opportunity Announcement (FOA) Number
Only one application per institution is allowed Section III. 3. Additional Information on Eligibility.
Catalog of Federal Domestics Assistance (CFDA) Number(s)
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.
December 3, 2010
Open Date (Earliest Submission Date)
Letter of Intent Due Date
January 4, 2011
Application Due Date(s)
Standard dates February 4, 2011.
AIDS Application Due Date(s)
Scientific Merit Review
Standard dates July, 2011
Advisory Council Review
Standard dates August, 2011
Earliest Start Date(s)
Standard dates September, 2011
February 5, 2011
Due Dates for E.O. 12372
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 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:
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.
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
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.
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:
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For profit 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.
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
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
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:
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.
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:
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:
In addition to the instructions above regarding the three Research Plan sections, the application should include the following.
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
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
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
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
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.
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?
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?
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?
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?
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.
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.
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.
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
As part of the scientific peer review, all applications will:
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:
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
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:
The P.I. of a center will:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility include:
The Steering Committee will:
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.
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)
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)
Adam L. Felsenfeld, Ph.D.
National Human Genome Research Institute()
Joseph D. Mosca, Ph.D., M.B.A.
Center for Scientific Review
National Institutes of Health
Phone: 301 408-9465
Grants Management Branch()
Telephone: 301- 496-7531
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.
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