CENTERS OF EXCELLENCE IN CHEMICAL METHODOLOGIES AND LIBRARY DEVELOPMENT
RELEASE DATE: December 17, 2002
RFA: GM-03-004 (Reissued as RFA-GM-08-007)
National Institute of General Medical Sciences (NIGMS)
(http://www.nigms.nih.gov)
LETTER OF INTENT RECEIPT DATE: January 24, 2003
APPLICATION RECEIPT DATE: February 20, 2003
THIS RFA CONTAINS THE FOLLOWING INFORMATION
o Purpose of this RFA
o Research Objectives
o Mechanism of Support
o Funds Available
o Eligible Institutions
o Individuals Eligible to Become Principal Investigators
o Special Requirements
o Where to Send Inquiries
o Letter of Intent
o Submitting an Application
o Peer Review Process
o Review Criteria
o Receipt and Review Schedule
o Award Criteria
o Required Federal Citations
PURPOSE OF THIS RFA
The purpose of this RFA is to reannounce and to update the National
Institute of General Medical Sciences (NIGMS) program of "Centers of
Excellence in Chemical Methodologies and Library Development" (CMLD
Centers), last issued as RFA-GM-01-006 in June 2001.
The goal of this program is to stimulate the establishment of multi-
investigator research centers whose mission will be to develop
efficient, general, state-of-the-art methodologies for the design,
synthesis, analysis, and handling of chemical diversity libraries. The
CMLD Centers will feature collaborations and team approaches that
otherwise would not be established, including individuals from various
subdisciplines within the field of chemistry and/or from cognate
fields, that will develop novel enabling methodologies.
Each Center will establish a library synthesis core facility that will
serve two purposes. First, the library synthesis core will validate
newly-developed methodologies for application to diversity-oriented
synthesis (also known as combinatorial chemistry). Second, the library
synthesis core will apply newly-developed chemical methodologies and
strategies to the generation of chemical diversity libraries for high-
throughput biological screening. This will provide "real world" tests
of the utility of new methodologies and will also facilitate the study
of complex biological phenomena. Each Center must develop a plan for
outreach to the biology research community.
The essential goals of the CMLD Centers program are to discover and to
implement fundamental new chemistry that will facilitate access to
high-quality libraries of expanded diversity.
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.
Until recently, the predominant approach to drug discovery has involved
in vivo and/or in vitro testing of individual, purified compounds, both
natural and synthetic, for physiological properties such as
cytotoxicity or antibiotic activity. These screens have tended to be
labor-intensive, slow, and expensive. However, the last decade has
witnessed major breakthroughs in the identification of genes, gene
products, metabolic pathways, and signaling pathways, as well as
progress in miniaturization and automation technologies. These
advances have led to the development of highly specific, mechanism-
based biological assays that are rapid, inexpensive, and compatible
with automation. The new assays have, in turn, 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.
Historically, most drug leads have been either isolated from natural
sources (e.g., plants, marine organisms, or microorganisms),
synthesized individually from inexpensive starting materials, or
obtained by chemical modification of natural products. Molecules
obtained from natural sources exhibit tremendous structural diversity
as well as a great variety of bioactivities. However, the collection
of source materials and the isolation, separation, and purification of
the constituent bioactive principles are relatively labor-intensive and
time-consuming. De novo synthesis of individual natural product (or
natural product-derived) molecules is similarly demanding.
Concurrent with the aforementioned developments in bioactivity
screening, pioneering advances have been made in strategies and
techniques for diversity-oriented synthesis. Diversity-oriented
synthesis (also referred to as combinatorial chemical synthesis) is a
process by which multiple compounds (chemical libraries) are generated
simultaneously, in a predictable fashion, by using techniques that
involve parallel chemical transformations. Diversity-oriented
synthesis may use solid- or solution-phase reaction and product
isolation techniques. A library may be small (e.g., a few compounds)
or large (e.g., thousands or even millions of compounds), and it may
focus on a narrow or wide range of "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 a major approach for drug lead identification. Now,
however, limitations are becoming apparent. At this relatively early
stage in the development of diversity-oriented synthesis, the tools for
planning, synthesizing, encoding, and chemically analyzing libraries
are proving to be limited in both number and sophistication.
Significantly, many synthetic reactions that work well under more
standard conditions are not effective under the conditions that are
used for diversity-oriented synthesis, particularly if the library
components (or the reagents) are attached to a solid support. As a
simple example, catalytic hydrogenation using palladium on charcoal is
a common, high-yielding method for reducing olefins; however, catalytic
hydrogenation does not work well if the olefin is attached to a solid
support. Also, owing to the substantial, unique challenges that attend
separation and purification procedures in diversity-oriented synthesis,
only reactions that proceed cleanly, give high yields, and are
extremely tolerant of structural variations in the substrates are truly
useful. 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 the small number of 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 very few strategies and
synthetic methods that will lead in a predictable fashion to multiple
scaffold structures in a given library.
In contrast to the well-established use of retrosynthetic analysis for
designing "target-oriented" syntheses of individual molecules, the
strategies for planning diversity-oriented syntheses are not well
developed. Through retrosynthetic analysis, a synthesis is planned in
reverse, beginning with the final product. The investigator identifies
a reaction that could afford a particular product and then deduces the
structure of the required starting material. This process is repeated
until a set of easily-procured starting materials is identified that
can be converted, by using an appropriate sequence of reactions, to a
complex target structure. Since diversity-oriented synthesis produces
multiple products, it is not possible to use retrosynthetic analysis,
at least in its current form.
While the development of novel methodologies is a major goal of
academic chemists, the academic chemistry community has not generally
embraced the development of methods that are specifically applicable to
diversity-oriented synthesis. Similarly, 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 for making large libraries, and the unfamiliarity of
strategies for diversity-oriented versus traditional target-oriented
organic synthesis.
The limitations of current methodologies clearly restrict the degree of
structural complexity, the diversity, and the quality of libraries. It
has been suggested that the theoretically accessible "chemical
diversity space" is defined by approximately 10(E60) "small" molecular
structures (i.e., molecular weights of 500 or lower). Even today's
largest libraries sample only a tiny fraction of this potential
chemical diversity space. Leaders in the pharmaceutical industry
(where diversity-oriented synthesis is used extensively) view the
limitations of current methodology as a problem of considerable urgency
and a significant impediment to the identification of drug candidates
in new classes and with new mechanisms of action. Clearly, the same
concerns would apply to the use of libraries by academic biologists who
seek to discover new, specific, mechanism-based small molecule probes
of fundamental biological processes. 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
that will be 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, dependable library-related methodologies.
A workshop sponsored by NIGMS focusing on the needs and opportunities
in diversity-oriented synthesis affirmed the importance, timeliness,
and feasibility of stimulating further research in this area. There
was agreement that improvements in chemical methodology for the
development of chemical diversity libraries are necessary for this
approach to realize its full potential to benefit biomedical science
and human health. A summary of the August 19, 2000 workshop at NIGMS
may be found on the NIGMS web site at:
http://www.nigms.nih.gov/news/reports/chemical_diversity.html.
Elements and Organization of a CMLD Center of Excellence
A CMLD Center must be an integrated, coordinated project, with
interdependent subprojects that are described fully and justified in
the grant application. Collaborations and consortia are strongly
encouraged, and the interactive nature of the proposed research is a
key factor that will be evaluated in peer review. The benefits to be
achieved through the establishment of multidisciplinary teams and novel
collaborations, as opposed to working independently, should be
described fully. The applicant should identify clearly in the
abstract, and more fully in the research plan, the new capabilities
that are proposed to be developed, or what specific questions are to be
studied, as a result of the establishment of the Center.
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 might include (but 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;
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 of library
synthesis;
o methods of sample preparation for biological screening of libraries;
o encoding and identification of the structures of active compounds
within libraries;
o storage and maintenance of libraries; or
o managing data on chemical diversity libraries.
It is clear that 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. 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
subdisciplinary boundaries (e.g., organic, inorganic, analytical,
physical, computational, and polymer chemistry) and that feature
complementary (i.e., nonredundant) skills are particularly encouraged.
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, industry participants must be willing to abide by the CMLD
guidelines, including data sharing and handling of intellectual
property.
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
criteria 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.
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
high-throughput biological screening. This will provide "real world"
tests of the utility of new methodologies and will also promote new
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 (as necessary), 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 will 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.
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 both
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 in order to meet those scientific goals.
"Centers-without-walls" (i.e., 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. If the team includes
investigators from more than one institution, a "letter of intent to
collaborate with the applicant organization" signed by the appropriate
institutional official from each participating organization must be
included in the application.
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.
A timeline for the project should be presented. This timeline should
outline how the project's goals can be met within the time frame of a
CMLD grant. The timeline will also assist the investigators, NIGMS,
and its advisors in evaluating progress toward the project's goals.
d. External scientific advisory committee
Each CMLD Center should have an external advisory committee of research
scientists who are not involved in the Center, to provide independent
assessment and advice to the PI and staff. This committee should be
appointed by the PI and confer at least twice each year. In order to
maximize the pool of possible reviewers, the potential members of the
advisory committee should not be contacted or selected until after an
award has been made. Nevertheless, the applicant should describe the
criteria to be used in selecting the members of the external advisory
committee.
MECHANISM OF SUPPORT
This RFA, which is a one-time solicitation, will use the NIH P50 award
mechanism. Awards are expected to be made during September 2003 or
early in FY 2004. Diversity-oriented synthesis is a rapidly developing
field, and it is anticipated that most projects that can be initiated
now will have a limited lifetime during which support from NIGMS will
be appropriate, either because the project goals will have been
accomplished or the Center will have developed to the point that
support can be derived from other sources. Therefore, the total length
of support for any P50 Center under this program will be no more than
ten years (an initial five-year award followed by a single five-year
renewal). The applicant will be solely responsible for planning,
directing, and executing the proposed project.
FUNDS AVAILABLE
NIGMS intends to commit approximately $6 million in FY 2003 to fund up
to two new grants in response to this RFA. Up to two additional grant
awards, totaling approximately $6 million, may be made in early FY
2004, if the funds are available. An applicant may request a project
period of up to five years and a budget for direct costs (not counting
capital equipment and F&A costs for subcontracts) of up to $1.1 million
per year per Center. Inflationary increases in subsequent years (up to
a total of five years) will be allowed at a rate of up to 3% per year.
Because the library synthesis core may require significant capital
equipment, a well-justified request for an additional allowance (up to
$1.25 million) for the acquisition of capital equipment in the first
year of the project will be considered. The budget should be fully
justified and should include funds for attending the annual meeting
(see below). 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 RFA are contingent upon the availability of funds and the receipt
of a sufficient number of meritorious applications.
ELIGIBLE INSTITUTIONS
You may submit application if your institution has any of the following
characteristics:
o For-profit or non-profit organizations
o Public or private institutions, such as universities, colleges,
hospitals, and laboratories
o Units of State and local governments
o Eligible agencies of the Federal government
Foreign institutions are not eligible to apply for research center
grants. However, subcontracts to foreign institutions are allowable,
with sufficient justification.
INDIVIDUALS ELIGIBLE TO BECOME PRINCIPAL INVESTIGATORS
Any individual with the skills, knowledge, and resources necessary to
carry out the proposed research is invited to work with his or her
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups, as well as individuals with
disabilities, are always encouraged to apply for NIH programs.
SPECIAL REQUIREMENTS
NIGMS has adopted several policies that are applicable to the CMLD
research centers. Applicants must present plans for implementing these
policies, where appropriate.
Intellectual property: The NIH has an interest in ensuring that the new
inventions, including methods, technologies, strategies, and computer
software, that are developed through this program become available to
the research community conveniently and in a timely fashion. It is
expected that these inventions will be readily and broadly applicable
to research and to the development of products and knowledge that will
benefit public health. For this reason, applicants should develop and
propose specific plans for sharing the data, materials, and software
generated through the grant, taking into consideration the recent
Guidance issued by NIH (http://www.nih.gov/od/ott/RTguide_final.htm).
The results of CMLD projects should be freely available for use by the
entire research community, consistent with the terms of the Bayh-Dole
Act (http://www.ucop.edu/ott/bayh.html).
The initial review group will comment on the proposed plan for data
sharing and release, including publication of results and product
licensing (where appropriate). The adequacy of the plan will also be
considered by NIH staff as one of the award criteria. The proposed
sharing plan, after negotiation with the applicant when necessary, will
be made a condition of the award. Evaluation of renewal applications
will include assessment of the effectiveness of data, materials, and
software release.
Applicants are also reminded that the grantee institution is required
to disclose each subject invention to the Federal Agency providing
research funds within two months after the inventor discloses it in
writing to the grantee institution personnel who are responsible for
patent matters.
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 two representatives of
each Center will attend this annual meeting at the NIH campus in
Bethesda, MD.
Post-award management: During the grant period, experimental
technologies will improve, and the rate of progress and the focus of
work supported by the grant may change. It is expected that the PI
will make any necessary adjustment in direction to accommodate a
changing scientific environment, keeping the NIGMS staff informed if
significant changes are made. In order to ensure that each Center
remains focused on appropriate goals, features truly integrated
approaches to science, incorporates new technological advances, and
makes sufficient progress, scientific and administrative visits to the
grantee may be conducted by NIGMS staff.
NIGMS may include outside consultants in the annual progress review and
may reduce or withhold funds in the case of limited progress toward the
goals of the CMLD program. A report by the NIGMS program director on
each Center's progress and recommendations to modify funding may be
made annually to the National Advisory General Medical Sciences
Council.
WHERE TO SEND INQUIRIES
We encourage inquiries concerning this RFA 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:
o Direct your questions about scientific/research issues to:
John M. Schwab, Ph.D.
Division of Pharmacology, Physiology, and Biological Chemistry
National Institute of General Medical Sciences
National Institutes of Health
Building 45, Room 2AS.43A
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-5560
FAX: (301) 480-2802
Email: schwabj@nigms.nih.gov
o Direct your questions about peer review issues to:
Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
National Institutes of Health
Building 45, Room 3AN.12P
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-2881
FAX: (301) 480-8506
Email: sunshinh@nigms.nih.gov
o Direct your questions about financial or grants management matters
to:
Ms. Antoinette Holland
Grants Management Office
National Institute of General Medical Sciences
National Institutes of Health
Building 45, Room 2AN.50B
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-5132
FAX: (301) 480-2554
Email: hollanda@nigms.nih.gov
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that
includes the following information:
o Descriptive title of the proposed research
o Name, address, and telephone number of the Principal Investigator
o Names of other key personnel
o Participating institutions
o Number and title of this RFA
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 NIGMS 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
Bldg. 45, Room 2As.43A
45 Center Drive, MSC 6200
Bethesda, MD 20892-6200
Telephone: (301) 594-5560
FAX: (301) 480-2802
Email: schwabj@nigms.nih.gov
SUBMITTING AN APPLICATION
Applications must be prepared using the PHS 398 research grant
application instructions and forms (rev. 5/2001). The PHS 398 is
available at https://grants.nih.gov/grants/funding/phs398/phs398.html in
an interactive format. For further assistance contact GrantsInfo,
Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.
SUPPLEMENTAL INSTRUCTIONS: 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
https://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 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); (r) letters of collaboration; etc. 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, 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, preliminary studies, and research design and methods, and
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.
Note that there is no requirement to submit the maximum number of
pages; instead, concise, articulate applications are strongly
encouraged.
USING THE RFA LABEL: The RFA label available in the PHS 398 (rev.
5/2001) application form 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:
https://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
SENDING AN APPLICATION TO THE NIH: Submit a signed, typewritten or
machine printed 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
Bethesda, MD 20817 (for express/courier service)
At the time of submission, two additional copies of the application,
including all appendices, must be sent to:
Helen R. Sunshine, Ph.D.
Chief, Office of Scientific Review
National Institute of General Medical Sciences
Building 45, Room 3AN.12P
45 Center Drive, MSC 6200
National Institutes of Health
Bethesda, MD 20892-6200
APPLICATION PROCESSING: Applications must be received by the
application receipt date listed in the heading of this RFA. If an
application is received after that date, it will be returned to the
applicant without review.
The Center for Scientific Review (CSR) will not accept any application
in response to this RFA that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application. The CSR will not accept any application that is
essentially the same as one already reviewed. This does not preclude
the submission of substantial revisions of applications already
reviewed, but such applications must include an Introduction addressing
the previous critique.
PEER REVIEW PROCESS
Upon receipt, applications will be reviewed for completeness by the CSR
and responsiveness by NIGMS.
Incomplete and/or non-responsive applications will be returned to the
applicant without further consideration.
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 receive a written critique. It is also possible that applications
will undergo a process in which only those applications deemed to have
the highest scientific merit, generally the top half of the
applications under review, will be discussed and assigned a priority
score. Finally, all applications will receive a second level review by
the National Advisory General Medical Sciences Council.
It is unlikely that site visits or applicant interviews will be
performed as part of the initial review. You should not assume that
they will be conducted; therefore, you must present a complete and
well-justified written proposal.
REVIEW CRITERIA
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In order to judge the likelihood that the proposed research will have a
substantial impact on the pursuit of these goals, the reviewers will be
asked to discuss in their written comments the following aspects of
your application:
o Significance
o Approach
o Innovation
o Investigator
o Environment
The scientific review group will address and consider each of these
criteria in assigning your application's overall score, weighting them
as appropriate for each application. Separate scores will not be
assigned for each subproject; however the scientific merit of each
subproject will be assessed, based on its merit as an independent
effort and its potential importance/contribution to the success of the
overall effort. Core facilities and resources will be assessed for
their quality, cost-effectiveness, and utility to the overall effort.
(1) SIGNIFICANCE: How likely is it that any proposed methodologies,
research tools, software, strategies, etc., will have a broad impact on
the production of high-quality, highly diverse chemical libraries?
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? What is the likely effect of the proposed
research on the field, and what is the likely impact on the larger
scientific community? If the aims of the application are achieved, how
will scientific knowledge be advanced?
(2) APPROACH: How strong is the scientific research plan? What is the
likelihood that the proposed research plan will achieve the stated
aims? Are the conceptual framework, design, methods, analyses,
techniques, and technologies adequately developed, well integrated, and
appropriate to the aims of the project? Are potential problem areas
acknowledged and alternative tactics proposed? 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--to validate new
methodologies and to produce high-quality libraries for biological
screening?
(3) INNOVATION: Does the project employ novel concepts, approaches or
methods? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
(4) INVESTIGATOR: Are the scientific training, background, and
expertise of the Principal Investigator and key personnel appropriate
to achieving the specific aims and overall goals of the proposed
research? Do the skills of the key personnel complement one another in
a manner that is appropriate to an integrated, team-oriented 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? Are the library synthesis core personnel qualified
for their role in the Center? Are the levels of effort of the key
personnel adequate?
(5) ENVIRONMENT: Does the scientific environment in which the work
will be done, including space, equipment, services, infrastructure, and
facilities, contribute to the probability of success? Does the
proposed research Center take advantage of 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?
ADDITIONAL REVIEW CRITERIA: In addition to the above criteria, the
application will also be reviewed with respect to the following:
o 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;
o 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;
o PROTECTIONS: The adequacy of the proposed protection for humans,
animals, or the environment, to the extent they may be adversely
affected by the project proposed in the application;
o DATA SHARING: The adequacy of the proposed plan to share data; the
plan for addressing intellectual property issues, including the
dissemination of intellectual and material products of this research,
as well as mechanisms for the licensing of CMLD-supported inventions
that are patented by a CMLD grantee;
o BUDGET: The appropriateness of the proposed budget and the requested
period of support in relation to the proposed research.
RECEIPT AND REVIEW SCHEDULE
Letter of Intent Receipt Date: January 24, 2003
Application Receipt Date: February 20, 2003
Peer Review Date: June/July 2003
Council Review: September 2003
Earliest Anticipated Start Date: September 15, 2003
AWARD CRITERIA
Applications will compete for available funds with all other approved
applications assigned to NIGMS. Awards will be made on or before
September 30, 2003. The following factors will be considered in making
funding decisions:
o responsiveness to the goals and objectives of the RFA;
o scientific merit, as determined by peer review;
o overall contribution of the project to the knowledge and experience
required to advance the state of the art in the planning, generation,
and/or analysis of chemical diversity libraries;
o program priority of research in this area and other areas of NIGMS
interest;
o plans for rapid and effective dissemination of the results and
information on technological developments; and
o availability of funds.
REQUIRED FEDERAL CITATIONS
PUBLIC 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 public 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
https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this RFA 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.
URLs IN NIH GRANT APPLICATIONS OR APPENDICES: All applications and
proposals for NIH funding must be self-contained within specified page
limitations. Unless otherwise specified in an NIH solicitation, Internet
addresses (URLs) should not be used to provide information necessary to
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 No. 93.859, and is not subject to the
intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review. Awards are made under authorization of
Sections 301 and 405 of the Public Health Service Act as amended (42
USC 241 and 284) and administered under NIH grants policies described
at https://grants.nih.gov/grants/policy/policy.htm and under Federal
Regulations 42 CFR 52 and 45 CFR Parts 74 and 92.
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.
https://grants.nih.gov/grants/guide/pa-files/PA-02-015.html.