Part I Overview Information


Department of Health and Human Services

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

Components of Participating Organizations
National Institute of General Medical Sciences (NIGMS), (http://www.nigms.nih.gov/)

Title: Centers of Excellence in Chemical Methodologies and Library Development (P50)

Announcement Type
This is a reissuance of RFA-GM-03-004. which was previously released on December 17, 2002

Request For Applications (RFA) Number: RFA-GM-08-007

Catalog of Federal Domestic Assistance Number(s)
93.859

Key Dates
Release Date:  October 17, 2007
Letters of Intent Receipt Date: December 14, 2007
Application Receipt Date: January 8, 2008
Peer Review Date: May-July 2008
Council Review Date: October 2008
Earliest Anticipated Start Date: September 30, 2008
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date: January 9, 2008

Due Dates for E.O. 12372
Not Applicable

Additional Overview Content

Executive Summary

Table of Contents


Part I Overview Information

Part II Full Text of Announcement

Section I. Funding Opportunity Description
  1. Research Objectives

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

Section III. Eligibility Information
  1. Eligible Applicants
    A. Eligible Institutions
    B. Eligible Individuals
  2.Cost Sharing or Matching
  3. Other - Special Eligibility Criteria

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

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

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

Section VII. Agency Contact(s)
  1. Scientific/Research Contact(s)
  2. Peer Review Contact(s)
  3. Financial/ Grants Management Contact(s)

Section VIII. Other Information - Required Federal Citations

Part II - Full Text of Announcement


Section I. Funding Opportunity Description


1. Research Objectives

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

Purpose of this RFA

The purpose of this FOA is to reannounce the National Institute of General Medical Sciences (NIGMS) "Centers of Excellence in Chemical Methodologies and Library Development" (CMLD Centers) program.  This RFA was originally issued in June 2001 as RFA-GM-01-006 and in December 2002 as RFA-GM-03-004, resulting in the award of four CMLD Center grants.  Both new and competing renewal applications will be accepted under this RFA.  It is not expected that this RFA will be reissued.

The overall mission of the CMLD program is to facilitate access to high-quality libraries and to an expanded range of chemical diversity via high-throughput chemical techniques.  Specifically, CMLD Centers are multi-investigator research centers that develop efficient, general, state-of-the-art methodologies for the design, synthesis, analysis, and/or handling of chemical diversity libraries.  The CMLD Centers feature collaborations and team approaches that otherwise would not be established, including individuals from multiple subdisciplines within the field of chemistry and/or from cognate fields.  NIGMS expects these collaborations to be central to the CMLD program, elevating a successful CMLD center beyond a collection of largely-independent R01 projects. 

In addition to methods research projects, each Center includes a library synthesis core facility that serves two purposes.  First, the library synthesis core validates newly-developed methodologies for application to high-throughput synthesis (also known as combinatorial chemistry, combichem, or diversity-oriented synthesis).  Second, the library synthesis core applies newly-developed chemical methodologies and strategies to the generation of chemical diversity libraries for high-throughput biological screening.  This provides "real world" tests of the utility of new methodologies and also contributes to research on complex biological phenomena.  To maximize the biomedical impact from the synthesis and screening of its chemical libraries, each Center must implement a plan for outreach to the biology research community.

RESEARCH OBJECTIVES

Background

Consistent with the stated mission of NIGMS, which is to support "basic biomedical research that is not targeted to specific diseases, but that increases understanding of life processes...," the rationale behind this RFA is that advances in fundamental, enabling methodologies for chemical diversity libraries will produce lasting benefits for all of biomedical science, including biology and medicine.

The last 15 years have seen the development of highly specific, mechanism-based biological assays that are rapid, inexpensive, and compatible with automation.  The new assays have revolutionized the discovery of small molecules with powerful physiological effects.  Not surprisingly, the ability to screen massive numbers of compounds quickly using these new technologies has stimulated the demand for collections of structurally diverse molecules. 

Concurrent with these developments in screening, pioneering advances have been made in strategies and techniques for high-throughput chemical synthesis.  This is a process by which multiple compounds (chemical libraries) are generated simultaneously, in a predictable fashion, by techniques that involve parallel chemical transformations.  A chemical library may be small (e.g., a few compounds) or large (e.g., tens of thousands of compounds), and it may sample a narrow or wide range of "chemical diversity space."  When subjected to high-throughput biological screening, chemical diversity libraries offer unprecedented opportunities for the rapid identification of small molecules with significant physiological effects.

The early success of this new strategy has led quickly to its widespread adoption, particularly in the pharmaceutical industry, where it has become the major approach for drug lead identification.  Now, however, limitations are apparent.  Specifically, the tools for planning, synthesizing, and chemically analyzing libraries are proving to be limited in both number and sophistication.  Significantly, many synthetic reactions that work well under standard conditions are not effective under the conditions that are used for high-throughput synthesis.  Also, owing to the substantial, unique challenges that attend separation and purification procedures in high-throughput synthesis, there is particular value in reactions that proceed cleanly, give high yields, and are extremely tolerant of structural variations in the reactants.  This severely limits the number of reactions that may be employed reliably.  Even for reactions that do work for library synthesis, extensive time and effort must be invested in process development and optimization prior to synthesis of the actual library. 

Significantly, although screening of chemical diversity libraries is firmly established for the identification of drug leads in the pharmaceutical industry, relatively few novel library-related methodologies are being published by industrial chemists.  While this may be due, in part, to intellectual property concerns, the pharmaceutical industry's focus on discovering and developing commercial drug products limits the resources that are available for more basic types of research.  Thus, the emphasis in industry is on the screening of both existing libraries and libraries that can be synthesized rapidly by a limited number of currently available methodologies.  

Another factor that limits library diversity is that practitioners tend to reuse core scaffolds that have been used successfully in the past.  This is because (a) the derivatization chemistry is well understood and (b) these scaffolds are known to have acceptable biological properties.  Furthermore, the vast majority of the libraries that have been synthesized include molecules based upon a single core structure per library, with the structural variations confined to peripheral substituents.  There are fewer strategies and synthetic methods that will lead in a predictable fashion to multiple scaffold structures in a given library. 

While the development of novel methodologies is a major goal of academic chemists, until recently, the academic chemistry community has not embraced the development of methods that are specifically applicable to high-throughput synthesis.  Similarly, relatively few academic chemistry labs routinely synthesize libraries for screening by biology collaborators.  The reasons for the limited involvement of academic chemists may include the burdensome nature of process development, the high cost of equipment dedicated to high-throughput synthesis, and the unfamiliarity of strategies for high-throughput versus traditional target-oriented organic synthesis. 

The limitations of current methodologies restrict the degree of structural complexity, the structure types that are accessible, and the quality of libraries.  It has been suggested that the theoretically accessible chemical diversity space is defined by approximately 10^60 small molecular structures (i.e., molecular weights of 500 or lower).  Even today's largest compound collections (fewer than 10^7 compounds) sample only a tiny fraction of this potential chemical diversity space.  Leaders in the pharmaceutical industry (where high-throughput synthesis is used routinely) view the limitations of current methodology as a significant impediment to the identification of drug candidates in new classes and with new mechanisms of action.  Clearly, analogous concerns apply to the use of libraries by academic biologists who seek to discover new, specific, mechanism-based small molecule probes of fundamental biological processes (cf. the NIH Roadmap’s Molecular Libraries Program; http://nihroadmap.nih.gov/molecularlibraries/).

Thus, it is evident that reliance on current techniques for producing and evaluating chemical libraries will limit the ability to capitalize on the plethora of new targets being uncovered through research in proteomics and functional genomics.  The goal of the CMLD initiative is to address these limitations by attracting the best academic chemists to the development of a wide range of versatile, robust, library-related methodologies.

Elements and Organization of a CMLD Center of Excellence

As stated above, each CMLD Center must be an integrated, coordinated project, featuring collaborations and team approaches that render it more than a collection of largely-independent R01 projects.  Project integration may be reflected in the scientific interdependence of the subprojects and/or shared leadership of the subprojects.  It also should be evident in the governance of the Center.  The integration of the proposed research projects and of the research team is a key factor that will be assessed in peer review. 

The benefits to be achieved through the establishment of multidisciplinary teams and novel collaborations, as opposed to working independently, must be described fully.  The applicant should identify clearly in the abstract, and more fully in the research plan, the new methodological capabilities that will be developed, or the specific questions to be studied.  The focus of the center must be on developing new methodologies rather than on generating and screening libraries.

The minimum requirements for a CMLD Center will be three research projects, three faculty-level participants (but not necessarily one per project), and a library synthesis core.  NIGMS is not specifying a maximum number of projects or participants; rather, the size of a CMLD Center should be a function of the science as well as the available funds (see below).  Additional cores (e.g., an administrative core) or shared resources may be proposed as appropriate to each Center.  The anticipated effectiveness of the proposed Center structure will be a criterion of the peer review evaluation prior to an award and will be monitored after an award is made.

a. Research projects on methodology development

Examples of topics that would be appropriate for investigation within a CMLD Center could include (but will not be limited to) the following: 

o     chemical reactions that will increase the diversity and/or quality of chemical libraries;

o     new core scaffolds;

o     methods for chemically derivatizing scaffolds;

o     solid supports and linkers for library intermediates, reagents, or scavengers;

o     new strategies for generating structural diversity;

o     fractionation, purification, and reagent scavenging techniques;

o     assessment of library purity and diversity;

o     strategies and/or instrumentation for automation, acceleration, and/or miniaturization of library synthesis;

o     methods of sample preparation for biological screening of libraries; or

o     storage and maintenance of libraries.

Innovations in one aspect of library methodology research will stimulate complementary advances in others.  For instance, new polymeric supports may prompt developments in linker or sample purification technology; new core scaffolds may influence the development of linkers as well as derivatization chemistry; and new reaction methodologies may lead to changes in library design strategies.  Furthermore, collaborations among teams of scientists with complementary perspectives and skills can lead to breakthroughs that would not be realized by a team led by a single investigator. 

Thus, for maximum impact, Centers should feature broadly-diversified research teams.  While chemists from any subdiscipline may participate in a CMLD Center, collaborations that cross traditional boundaries (e.g., organic, inorganic, analytical, physical, computational, or polymer chemistry, or chemical engineering) and that feature complementary (i.e., clearly distinct) skills and scientific perspectives are strongly encouraged. 

During the initial phase of the CMLD program, nearly all of the research projects have focused on chemical reaction methodology and on the generation of novel scaffolds.  In the upcoming phase of the program, each Center must diversify its research portfolio, by including at least one project that does not focus on organic synthesis. 

Applicants should describe collaborative research projects as well as mechanisms for promoting scientific interactions among the participants.  Plans must be presented for effective team communication and coordination of effort that covers the development, implementation, and conduct of all aspects of the research program.  The degree of synergy among the participating research groups and the benefits that may be expected to result from these interactions will be major considerations in peer review and in NIGMS funding decisions.  It is essential to justify the proposed Center in terms of the "value added" beyond what would be expected from a set of independent R01-style projects.

Participants in a CMLD Center may come from the same or different departments of a single academic institution or from different institutions, and they may come from industry as well as academia.  However, industrial participants must be willing to abide by the CMLD guidelines, including data sharing and handling of intellectual property.

b. Library synthesis core facility

Each Center must establish a core facility for the synthesis of high-quality chemical libraries.  The purpose of this core will be two-fold.  First, it will validate newly-developed methodologies in the context of chemical diversity libraries.  Second, it will apply these new chemical methodologies and strategies to the generation of actual libraries for biological screening.  This will provide "real world" tests of the utility of new methodologies and will also promote interdisciplinary approaches for studying complex biological phenomena.  The staff of the core synthesis facility must have the administrative and technical skills to ensure smooth operation for the validation and optimization of new methodologies, as well as for the application of new methodologies to the synthesis of libraries for screening.  Applicants should describe the scientific function of the library synthesis core, including the approaches to be used for optimizing and validating new methodologies; the design strategies and methods that will be used for the synthesis, purification, sample handling, and analysis of actual libraries; and protocols to be used for archiving and analyzing both the data and the compounds that are generated by the library synthesis core.  Funding for process validation studies and for most library syntheses may be included in the P50 Center budget.

As the focus of the CMLD Centers program is on chemical methodology rather than biology, biological screening will best be accomplished via interdisciplinary collaboration involving the library synthesis core.  Such collaborations must merge innovative chemistry with innovative and significant biology.

The library synthesis core must provide samples (10-20 mg per compound) to the NIH Molecular Libraries Small Molecule Repository (http://mli.nih.gov/mlsmr/index.php) for high-throughput screening by the Molecular Libraries Probe Production Centers Network (http://grants.nih.gov/grants/guide/pa-files/PAR-07-368.html).

Applicants should describe the management plan for the library synthesis core.  There must be representation by the biological research community in the administration and/or oversight of the core, and a strategy should be presented for outreach to the biological research community in order to develop collaborative projects.  The administrative plan should indicate how requests for libraries will be prioritized, in the event that the demand outstrips the capacity to produce libraries. 

c. Administration and management

Due to the inherent complexity of the Center structure, including collaborative and/or interdependent research projects as well as shared resources, a well thought-out and carefully described management plan that ensures that the interests of all CMLD participants are represented will be required.  Whether or not an administrative core is specified, plans must be presented for the proper administration of the Center.  The P50 grant application should specify the administrative and organizational structure(s) that will be used to support the research, and the synergies enabled by those structures. 

The PI will be responsible for ensuring that scientific goals are met, and for developing and managing a decision-making structure and process that will allow resources to be allocated equitably, in order to meet those scientific goals.  To that end, PI must describe how the scientific focus will be maintained in the overall project and in each of the subprojects, as well as the measures to ensure that progress is strong and steady.

Centers that involve participants from more than one physical site are welcome under this solicitation.  If any of the components is physically separated from the others (e.g., different departments or institutions), the applicant should describe how interactions will be facilitated.  The signature of the authorized organizational official on the Face Page signifies that the applicant and all proposed consortium participants understand and agree to the following statement: The appropriate programmatic and administrative personnel of each organization involved in this grant application are aware of the NIH consortium agreement policy and are prepared to establish the necessary inter-organizational agreement(s) consistent with that policy.  A separate statement is no longer required.

Projects of the anticipated degree of complexity, both scientific and managerial, will require a substantial investment of the PI's effort.  The PI will be required to devote sufficient effort to ensure successful leadership and implementation of the goals of the Center.  

d. External scientific advisory board

Each CMLD Center must have an external advisory board (EAB) of research scientists who are not involved in the Center, to provide independent assessment and advice to the PI and other Center participants.  The EAB will be appointed by the PI and must confer in person for a substantive meeting at least once each year.  In the case of new applications, the PI must describe the criteria to be used in selecting the members of the EAB as well as the mechanisms by which the EAB’s input will be solicited and utilized to guide the operation of the Center.  For existing CMLD Centers, the names and affiliations of continuing EAB members should be provided, along with a brief description of the specific expertise/perspective provided by each EAB member.  If there are gaps in the EAB’s collective expertise that need to be filled, then these should be identified.

Section II. Award Information


1. Mechanism(s) of Support

This funding opportunity will use the P50 award mechanism.  This is a one-time solicitation.  As an applicant, you will be solely responsible for planning, directing, and executing the proposed project.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application.

2. Funds Available

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

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

Section III. Eligibility Information


1. Eligible Applicants

1.A. Eligible Institutions

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

Foreign institutions are not eligible to apply for research center grants.  However, subcontracts to foreign institutions are allowable, with appropriate justification.

1.B. Eligible Individuals

Any individual with the skills, knowledge, and resources necessary to carry out the proposed research is invited to work with their institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

2. Cost Sharing or Matching

Cost sharing is not required under this FOA.

The most current Grants Policy Statement can be found at: http://grants.nih.gov/grants/policy/nihgps_2003/nihgps_Part2.htm#matching_or_cost_sharing

3. Other-Special Eligibility Criteria

Upon receipt, applications will be reviewed for completeness by CSR and responsiveness by NIGMS

Applicants may submit more than one application, provided each application is scientifically distinct.  Applications for new grants as well as competing renewals all are eligible.
Resubmissions (formerly referred to as “revised applications”) of unfunded applications submitted in response to previous versions of this FOA should be submitted as new applications rather than as resubmissions. 

Section IV. Application and Submission Information


1. Address to Request Application Information

The PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 435-0714, Email: GrantsInfo@nih.gov.

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

2. Content and Form of Application Submission

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

The title and number of this funding opportunity must be typed on line 2 of the face page of the application form and the YES box must be checked.

The application should include: (a) a single face page for the entire application; (b) abstract; (c) key personnel listing; (d) table of contents; (e) the consolidated budget for the entire CMLD grant [summarizing budgets for the component parts and core(s)]; (f) individual project and core budgets; (g) biographical sketches for all key personnel; (h) other sources of research support (both current and pending) for all key personnel (see http://grants.nih.gov/grants/funding/phs398/instructions2/p3_other_support.htm); (i) resources and facilities (including major instruments and special program resources); (j) institutional support; (k) project overview (including a description of the overall scope and objectives; (l) justification of the P50 Center mechanism, including a description of the synergy among the participants, the research projects, and the other components of the Center and a discussion of how the scientific goals will be furthered via the P50 Center grant mechanism in ways that would not be readily attainable through individual research project grants; (m) plans for administrative management; (n) plans for project management; (o) plans for handling intellectual property issues; (p) project descriptions; (q) description(s) of core(s); and (r) letters of collaboration.  Section (h) must also detail the relationship of other support to the proposed Center and describe anticipated modifications to that support in the event of funding (e.g., folding in support for related, already funded research). 

Each project description should include (in the following order) a cover page, an abstract, budget pages, and a detailed research plan.  The research plan should be organized as specified in the PHS 398 application form; i.e., it should include specific aims, background and significance, progress report/preliminary studies, and research design and methods.  The usual 25 page limit will apply.  The special benefits (to the project) of being associated with the Center must also be addressed. 

Each core facility should be described in no more than 20 pages, in addition to the budget pages for that particular core.  Separate sections describing and justifying the core resource(s) should be included.  Sections (j) through (o) of the application (see above) should be presented in no more than 30 pages.  For renewal applications, section (l) should include a discussion of progress to date, in addition to the topics that are specified above.

Note that there is no requirement to submit the maximum number of pages; to the contrary, concise, articulate applications are strongly encouraged.

This funding opportunity uses the just-in-time budget concepts. It also uses the non-modular budget format described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html). A detailed categorical budget for the "Initial Budget Period" and the "Entire Proposed Period of Support" is to be submitted with the application, as described above.

3. Submission Dates

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

3.A. Receipt, Review and Anticipated Start Dates
Letters of Intent Receipt Date: December 14, 2007
Application Receipt Date: January 8, 2008
Peer Review Date: May-July 2008
Council Review Date: October 2008
Earliest Anticipated Start Date: September 30, 2008

3.A.1. Letter of Intent

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

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

The letter of intent is to be sent by the date listed at the beginning of this document.

The letter of intent should be sent to:

John M. Schwab, Ph.D.
Division of Pharmacology, Physiology, and Biological Chemistry
National Institute of General Medical Sciences
45 Center Drive, Room 2As.43A
MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-3827
FAX: (301) 480-2802
Email: schwabj@nigms.nih.gov


3.B. Sending an Application to the NIH

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

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

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

At the time of submission, two additional copies of the application and all copies of the appendix material must be sent to:

Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
45 Center Drive, Room 3AN.12F
MSC 6200
National Institutes of Health
Bethesda, MD  20892-6200
Telephone: (301) 594-2881
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov


Using the RFA Label: The RFA label available in the PHS 398 application instructions must be affixed to the bottom of the face page of the application. Type the RFA number on the label. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. The RFA label is also available at: http://grants.nih.gov/grants/funding/phs398/labels.pdf.

3.C. Application Processing

Applications must be received on or before the application receipt date(s) described above (Section IV.3.A.). If an application is received after that date, it will be returned to the applicant without review. Upon receipt, applications will be evaluated for completeness by CSR and responsiveness by NIGMS. Incomplete and non-responsive applications will not be reviewed.

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

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

4. Intergovernmental Review

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project. See NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.

6. Other Submission Requirements

Annual meeting:  Applicants should plan to attend an annual meeting of CMLD awardees, in order to present results and to discuss issues of common interest or concern.  For the purpose of preparing an appropriate budget, it should be presumed that at least two representatives of each Center will attend this annual meeting.  Participating faculty, graduate students, postdoctoral associates, Center staff, and external advisory board members all are encouraged to attend the scientific sessions of the CMLD annual meeting. 

The meeting will be hosted by each of the CMLD Centers, in turn, and it will be the responsibility of the hosting Center to plan the program (with approval from NIH staff) and to advise attendees regarding local arrangements.  At its discretion, NIGMS may consider the award of supplemental funds to defray the allowable costs incurred in hosting the meeting; however, all requests for supplemental funds must include verification that funds are not otherwise available to cover these costs and could not be made available by rebudgeting from other cost categories.


Plan for Sharing Research Data

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

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

Sharing Research Resources

NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm#_Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of any resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of such resource sharing 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). See Section VI.3. Reporting.

Section V. Application Review Information


1. Criteria

The following will be considered in making funding decisions:

2. Review and Selection Process

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

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

The goals of NIH supported research are to advance our understanding of biological systems, to improve the control of disease, and to enhance health. In their written critiques, reviewers will be asked to comment on each of the following criteria in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that an application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative but is essential to move a field forward.

Significance: Does this study address an important problem? If the aims of the application are achieved, how will scientific knowledge be advanced? What will be the effect of these studies on the concepts, methods, technologies, services, or preventative interventions that drive this field? How likely is it that any proposed methodologies, research tools, software, strategies, etc., will have a broad impact on the production of high-quality chemical libraries, including regions of chemical diversity space heretofore inaccessible by high-throughput synthesis?  Will these new methodologies substantially enhance the availability of chemical diversity libraries for high-throughput biological screening?  Are the proposed strategies and technologies likely to be readily exportable?  How important are the proposed research areas and topics being explored, and how relevant are these research areas and topics to furthering the state of the art in developing high-quality chemical diversity libraries?

Approach: Are the conceptual or clinical framework, design, methods, and analyses adequately developed, well integrated, well reasoned, and appropriate to the aims of the project? Does the applicant acknowledge potential problem areas and consider alternative tactics? How much interplay and synergy are there among the projects and among the key personnel?  Are the interactions among the key personnel critical to achieving the stated goals?  Is the proposed structure of the library synthesis core facility (including staffing, procedures, management, and equipment) appropriate for meeting the goals of the core—i.e., to validate new methodologies and to produce high-quality libraries for biological screening?

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

Investigators: Are the investigators appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the principal investigator and other researchers? Does the investigative team bring complementary and integrated expertise to the project? Does the Principal Investigator have the appropriate management and administrative skills to lead and coordinate the activities, and to develop and implement the management plan, as required for the project's success?  Do the subproject leaders have appropriate scientific and managerial skills, as well as a commitment to team-oriented science?  Are the library synthesis core personnel qualified for their role in the Center?  Are the levels of effort of the key personnel adequate?

Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed studies benefit from unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support, including any needed expansion of facilities, improvement of infrastructure, and relief from other academic duties, where necessary?

Management and Administration: The suitability and quality of the management plan, including the management structure; the plan for deployment of equipment and human resources to attain the research aims and overall Center goals; the organization and coordination of the personnel; plans for making critical decisions or choices about overall research direction.

Outreach: The plans for outreach to the biomedical research community, including solicitation of interest in using chemical diversity libraries; and making libraries available for screening.


2.A. Additional Review Criteria:

In addition to the above criteria, the following will continue to be considered in the determination of scientific merit and the priority score:
Protection of Human Subjects from Research Risk: The involvement of human subjects and protections from research risk relating to their participation in the proposed research will be assessed (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Inclusion of Women, Minorities and Children in Research: The adequacy of plans to include subjects from both genders, all racial and ethnic groups (and subgroups), and children as appropriate for the scientific goals of the research will be assessed. Plans for the recruitment and retention of subjects will also be evaluated (see the Research Plan, Section E on Human Subjects in the PHS Form 398).

Care and Use of Vertebrate Animals in Research: If vertebrate animals are to be used in the project, the five items described under Section F of the PHS Form 398 research grant application instructions will be assessed.

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

2.B. Additional Review Considerations

Budget: The reasonableness of the proposed budget and the requested period of support in relation to the proposed research. The priority score should not be affected by the evaluation of the budget.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of data sharing plans or the rationale for not sharing research data will be assessed by the reviewers. However, reviewers will not factor any proposed data sharing plan into the determination of scientific merit or the priority score. The funding organization will be responsible for monitoring the data sharing policy.

2.D. Sharing Research Resources
NIH policy expects that grant recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (See the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps/part_ii_5.htm#availofrr and

http://grants.nih.gov/grants/intell-property_64FR72090.pdf). Investigators responding to this funding opportunity should include a sharing research resources plan addressing how unique research resources will be shared or explain why sharing is not possible.

3. Anticipated Announcement and Award Dates

N/A

Section VI. Award Administration Information


1. Award Notices

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

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant. For details, applicants may refer to the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part4.htm).

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization. The NoA signed by the grants management officer is the authorizing document. Once all administrative and programmatic issues have been resolved, the NoA will be generated via email notification from the awarding component to the grantee business official (designated in item 12 on the Application Face Page). If a grantee is not email enabled, a hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.

2. Administrative and National Policy Requirements

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).

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

The Terms and Conditions for any awards made under this FOA will include a requirement that the library synthesis core must provide samples (10-20 mg per compound) to the NIH Molecular Libraries Small Molecule Repository for high-throughput screening by the Molecular Libraries Probe Production Centers Network.

3. Reporting

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually (http://grants.nih.gov/grants/funding/2590/2590.htm) and financial statements as required in the NIH Grants Policy Statement.

Section VII. Agency Contacts


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

1. Scientific/Research Contact:

John M. Schwab, Ph.D.
Division of Pharmacology, Physiology, and Biological Chemistry
National Institute of General Medical Sciences
45 Center Drive, Room 2As.43A, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-3827
FAX: (301) 480-2802
Email: schwabj@nigms.nih.gov

2. Peer Review Contact:

Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
45 Center Drive, Room 3AN.12F, MSC 6200
National Institutes of Health
Bethesda, MD  20892-6200
Telephone: (301) 594-2881
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov

3. Financial or Grants Management Contact:

Ms. Lisa Moeller
Grants Management Officer
National Institute of General Medical Sciences
National Institutes of Health
45 Center Drive, Room 2AN.50C, MSC 6200
Bethesda, MD  20892-6200
Telephone:  (301) 594-3914
FAX:  (301) 480-5601
Email:  moellerl@nigms.nih.gov moellerl@nigms.nih.gov

Section VIII. Other Information


Required Federal Citations

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

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

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

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

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

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

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

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

URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles.  Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.

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

Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.

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

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


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices


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