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FUNCTIONAL ATLAS OF ORPHAN NUCLEAR RECEPTORS
Release Date: June 7, 2001
RFA: RFA-DK-01-026 (Reissued as RFA-DK-06-503)
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute on Aging
Letter of intent: October 17, 2001
Application Receipt Date: November 19, 2001
PURPOSE
The purpose of this initiative is to develop a Functional Atlas of
Orphan Nuclear Receptors emphasizing understanding and cataloging of
structure, tissue distribution, specificity, and function.
Nuclear hormone receptors, their ligands, and relevant accessory
proteins play important roles in development and aging, metabolism, and
disease, and comprise a large superfamily of receptors for a multitude
of hormones, xenobiotics, lipids, and other known and unknown ligands.
Knowledge of the function, structure, and specificities of these
receptors can serve as the basis for the development of therapeutics to
treat diseases, including diabetes, obesity, osteoporosis, heart
disease, and prostate and breast cancer. While a great amount of
information has already been uncovered, recent advances continue to
provide a wealth of new data that must be collated and analyzed. Thus,
further understanding of receptor specificity, ligand selectivity,
interaction with cytoplasmic and/or nuclear accessory proteins,
chromatin, and the transcriptional machinery, will require development
of a unique database to collect and integrate this information. It is
anticipated that this initiative will enhance coordination with
emerging genetic information from the human (and other) genome
effort(s). This initiative will focus specifically on one sub-group of
the superfamily, the orphan nuclear receptors (ONR).
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,
(Functional Atlas of Orphan Nuclear Receptors), is related to the
priority area of: Chronic Diseases. Potential applicants may obtain a
copy of "Healthy People 2010" at http://www.health.gov/healthypeople/.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges,
hospitals, laboratories, units of State and local governments, and
eligible agencies of the Federal Government. Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as principal investigators. In addition, collaborators from
foreign institutions are permitted.
MECHANISM OF SUPPORT
The funding instrument to be used for this program will be a Research
Program-Cooperative Agreement (U19), an assistance mechanism (rather
than an acquisition mechanism), in which substantial NIH scientific
and/or programmatic involvement with the awardee is anticipated during
performance of the activity. The U19 allows for support of a series of
components designed to explore a cohesive theme. Under the cooperative
agreement approach, the NIH purpose is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly
with the award recipient in a partner role, but it is not to assume
direction, prime responsibility, or a dominant role in the activity.
Details of the responsibilities, relationships and governance of the
study to be funded under cooperative agreement(s) are discussed later
in this document under the sections "TERMS AND CONDITIONS OF AWARD",
“OBJECTIVES AND SCOPE", and "SPECIAL REQUIREMENTS." Except as
otherwise stated in this announcement, awards will be administered
under NIH grants policy as stated in the NIH Grants Policy Statement
(http://grants.nih.gov/grants/policy/nihgps/). Funding is anticipated
before the end of FY 2002.
The total project period for applications submitted in response to the
present RFA may not exceed 5 years. The anticipated award date is
September 30, 2002. Awards and level of support depend on receipt of a
sufficient number of applications of high scientific merit.
FUNDS AVAILABLE
For Fiscal year 2002 $2.5 Million (Total Costs = Direct + Facilities
and Administrative Costs) will be committed by NIDDK to fund one
application in response to this RFA. In addition, the National
Institute on Aging has committed $0.5 Million (Total Costs) in support
of this initiative, for a total of $3.0 Million (Total Costs). Although
this program is provided for in the financial plans of the NIDDK and
NIA, the awards pursuant to this RFA are contingent upon the
availability of funds and receipt of a sufficient number of
applications of outstanding scientific and technical merit.
RESEARCH OBJECTIVES
Background
Nuclear receptors comprise a large family of hormone-dependent and -
independent transcription factors responsible for reproduction, growth,
differentiation, and homeostasis. The nuclear receptors are part of a
large superfamily consisting of receptors for steroid hormones
(estrogen, androgen, adrenal glucocorticoid, aldosterone, and
progesterone; ER, AR, GR, MR, and PR, respectively), nuclear hormones
(vitamin D, retinoids, thyroid hormone; VDR, RAR/RXR, TR,
respectively), and orphan nuclear receptors (peroxisome proliferator
activated receptor or PPAR, lipid receptors, COUP-TFI/II, SF-1, etc.).
The latter have functions in cells, during development and in the
adult, but with no, or only poorly, defined ligand(s). While some
orphan receptors have recently been classified as responding to defined
ligands (e.g. PPAR?), the identity of true natural ligands in most
instances remains to be elucidated.
Studies in model organisms have suggested that members of this
superfamily have a long evolutionary history, are well conserved in
lower organisms, and constitute a significant portion of known genomes
(Tsai and O'Malley, Ann. Rev. Biochem. 63:451-486, 1994; McKenna et al.
J. Steroid Biochem Mol Biol 69:3-12, 1999). With the rapid onset of
knowledge of the human genome, it is clear that nuclear receptors are
present in abundance in humans, as well (Lander et al., Nature 409:860,
2001), with both known and unknown functions. Moreover, it is
anticipated that with further annotation of the human genome other
orphan nuclear receptors will be discovered. While some of these
receptors will prove to have redundancies (e.g. Brown, et al. JCI
106:73-79, 2000), many will be found to be unique with specific
localizations and/or functional implications as well as implications
for disease (Lazar, J. Investig. Med. 47:364-368, 1999). Others may
have temporal specificities associated with developmental roles (Zhou
et al., Neuron 24:847-859, 1999). As additional genomic information
emerges, expression studies utilizing proteomics tools become an
important component of discovery.
Although primarily functioning as transcription factors, it has become
clear that the biology of these receptors is complex: they are often
bound to chaperone proteins in the cytoplasm, and/or to DNA in the
nucleus; they may bind to DNA as monomers, dimers, or heterodimers---
with or without ligand; they may interact with any of a number of
different classes of nuclear accessory and/or chromatin remodeling
proteins; the presence or absence of ligand can define interactions
with other proteins which foster the ability of the receptor to
activate or repress gene expression; and alterations in the receptor,
the ligand, or various of the accessory proteins, such as co-activators
and co-repressors, can have profound effects on development, and
protein/lipid/carbohydrate metabolism, and in diseases such as prostate
and breast cancer, and diabetes, obesity, heart disease, and
osteoporosis, as well as processes associated with aging. The
receptor, the ligand, and relevant accessory proteins can also serve as
the basis for the development of therapeutics to treat disease. To do
so, further research is required to fully understand the molecular
mechanism of action of these receptors, the underlying basis for tissue
specificity of action, the nature of cellular co-activator or co-
repressor usage, and the role(s) these may play in the development,
progression, and treatment of disease.
With this in mind, it has become clear that the vast amount of
information already available, coupled with the new information
emerging from model organisms and from the human genome project, calls
for a large-scale, collaborative effort designed to develop, categorize
and integrate knowledge of orphan nuclear receptors. To this end, the
U19 encompasses research projects and shared resources designed as part
of a collaborative effort to address the objectives of the program.
Objectives and Scope
Two overriding objectives govern this initiative: 1) collation and
characterization of information already in hand, and 2) new research to
more fully understand the role(s) of orphan nuclear receptors in
health, disease, and aging. In developing a Functional Atlas of Orphan
Nuclear Receptors, the long-term goal is to focus on orphan receptors
(e.g. PPAR, FXR, LXR, SXR, SF-1, CAR, COUP TFI/II, etc.), as well as
the cofactors and the ligands with which many interact to complete a
functional loop. Among these cofactors are those present in the
nuclear compartment (coactivators, corepressors, chromatin modifying
proteins and RNA transcripts, linkers, methylases, histone modifying
enzymes, etc.), as well as those in the cytoplasmic compartment
(chaperones, binding proteins, kinases/phosphatases). Beyond the scope
of this present initiative, but certainly relevant in functional
contexts, is consideration of the nuclear (VDR, RAR, RXR, TR), and
steroid (ER, AR, GR, MR, PR) receptors, as they intersect with ONRs.
Insights into the structures of several receptors both bound and
unbound to ligand and/or cofactor(s) have been revealed by x-ray
crystallographic and NMR studies. Discovery of natural and artificial
ligands has added much to our understanding of function. For some
Orphan Nuclear Receptors, role(s) in disease has preceded knowledge of
putative ligand(s), as for PPAR? and its role in adipogenesis and
insulin resistance in Type 2 diabetes mellitus. Indeed, based on less
than complete knowledge, several ligands directed at PPAR? have already
been developed for use as insulin sensitizing agents in the treatment
of Type 2 diabetes (e.g. thiazoladinediones;TZDs). The general concept
of Selective Receptor Modulators (SRMs) has evolved rapidly to include
clinical use of drugs with selective actions on nuclear receptor
function, such as TZDs for Type 2 diabetes and tamoxifen for estrogen-
dependent breast cancer. With greater knowledge of nuclear receptor
structure, tissue specificity, and function, in general, it will be
possible to develop more powerful and effective SRMs, many of which
will be relevant to ONRs.
Finally, while much is known about the expression and function of many
of the members of this family, studies exploiting gene knock-outs in
mouse transgenic models have revealed redundancies and levels of
compensation that confound our full understanding of the physiology of
many of the integral components of the hormone action loop.
Although it is desirable to create a unified Functional Atlas for the
entire Nuclear Receptor Superfamily, limited resources initially
available for this initiative do not at this time allow for development
of such a comprehensive program. While considerable information exists
regarding the structure and function of the steroid receptors and the
nuclear receptors, less information is currently available for the
orphan nuclear receptors (ONR). The ONRs have developed a central
importance as a consequence of their role(s) in development
(organogenesis) and metabolism (e.g. lipid and carbohydrate; see Chawla
et al., Cell 103:1-4, 2000), as well as aging. With this in mind, the
immediate focus of this initiative will be with development of a
Functional Atlas of Orphan Nuclear Receptors. To do so it is
envisioned that the final program will include research and development
in the following areas:
o Determination of tissue specificity: understanding and
cataloging levels and extent of expression in different
cells/tissues.
o Preference in cofactor usage: tissue specificity and context
of coactivator and/or corepressor usage; role of putative
ligand(s) in cofactor recruitment (binding/dissociation) and
function.
o Receptor domain structure and function: DNA and/or ligand
binding, transactivation, cofactor association.
o Receptor/DNA interaction: roles in and effects of chromatin
remodeling cofactors on regulation of transcription; roles of
receptor dimerization and (homo-, hetero-) dimer partner usage
(e.g. with nuclear receptors such as RXR).
o Regulation of expression: role(s) in development and aging;
signaling cross-talk; ligand feedback; receptor subtype
expression.
o Physiology/pathophysiology: issues of redundancy and/or
compensation; mutations and polymorphisms which affect
metabolic function and/or disease.
o Target for therapeutics: putative ligands, partial agonists,
antagonists, subtype specific factors (e.g. Selective Receptor
Modulators or SRMs).
o Orphan receptors in lower and model organisms: functional
correlations with mouse and/or human.
o New gene discovery based on data mining through genome
databases.
o Use of appropriate proteomics tools to determine the function
of orphan nuclear receptors, associated cofactors, or gene
targets.
While some of these objectives represent efforts to collect and catalog
what is already known, others require research efforts that may involve
novel and innovative approaches to develop needed information. In order
to maximize the resources available in a rich and diverse research
community, it is anticipated that a defined structure must be
developed, which will allow for development of a series of components,
defined as research projects and shared resources. The latter will
include Administrative, Bioinformatics (required elements), and other
shared resources as proposed by the applicant. The former (collectively
called Research Components) include bridging and pilot projects (at the
host institution or through appropriate subcontracts to other sites)
directed at delineation of specific components of the overall program
(see SPECIAL REQUIREMENTS). Since the primary objective of this large-
scale collaborative effort will be data integration, each contributing
project will include a plan that addresses data integration and an
interface with the Bioinformatics Resource. Full integration of data
with the Bioinformatics Resource will facilitate rapid dissemination of
new information, development of new hypotheses, and allow for data
mining via a web-based interface. Given the breadth of the task, a
large-scale collaborative effort (i.e., the U19 mechanism) is best
suited for development of a Functional Atlas of Orphan Nuclear
Receptors.
The objectives listed above suggest a scope for this initiative, and
they do not preclude additional objectives proposed in applications
responsive to this RFA.
To develop a Bioinformatics Resource for the Functional Atlas of Orphan
Nuclear Receptors it will also be necessary to include research and
development of the following objectives:
o Development of a functioning relational database as the basis
of a Bioinformatics Resource for the Functional Atlas of
Orphan Nuclear Receptors.
o Development of (and/or use of existing) software to enable
collection and analysis of data from many different sources
and formats, including cDNA and protein sequences,
microarrays, histopathological analysis, structural biological
analyses (e.g. NMR, X-ray crystallography), and other
databases and analytical tools.
o Regular curation of existing and emerging information,
including evaluation and annotation of data and incorporation
into appropriate databases; integration of information from
many different sources; database and interface design and
implementation.
o Development of appropriate algorithms to allow for rapid data
mining and in silico analyses of structural and functional
relatedness and/or gene discovery.
o Development of algorithms to facilitate interactive and
integrated analyses of function (e.g. metabolic flow charts).
o Providing for the maximal interoperability to facilitate the
ability to rapidly search other databases for related
information relevant to nuclear receptors, including
functional databases, lower (model) organisms databases (e.g.
Flybase (http://www.fruitfly.org/), and the human genome
project (e.g. National Center for Biotechnology Information).
o Development and maintenance of web tools and a web site for
the Functional Atlas which facilitates use on any platform.
o Provision of capability, by investigators of the Functional
Atlas program, to readily enter and access data.
Since the mechanism for this program is a cooperative agreement in the
form of a Research Program (U19), an overall collaborative protocol
will be developed at the time of initiation of funding by a Steering
Committee (see TERMS AND CONDITIONS OF AWARD), composed of the
awardee(s), individual project principal investigators, and the NIDDK
Program Scientist.
It is anticipated that intense and meaningful interactions between and
among the collaborating investigators involved in the U19 will result
in achievement of progress at a rate and in a fashion not possible for
the individual. While some of the information to be developed is
anticipated to be of a descriptive, but necessary, nature, other work
will involve new approaches and conceptual leaps that will be driven by
the collaborative nature of the interactions. In the application a
detailed explanation of the rationale should be provided, along with
definitive and progressive landmarks, with a timeline for the
achievement of the goals (see below and APPLICATION PROCEDURES).
Research Components, together with Shared Resources, should be
integrated to produce a collaborative effort that maximizes the
individual efforts and facilitates fulfillment of the overall
objectives of the Functional Atlas.
The expertise appropriate for this research program includes knowledge
of the molecular endocrinology, pharmacology, histology, and
pathophysiology of Orphan Nuclear Receptors. In addition, expertise in
development and use of transgenic models and of mouse genetics is
essential. Expertise in computational biology, bioinformatics,
genomics, proteomics, and phenotypic analysis is also highly
recommended.
SPECIAL REQUIREMENTS
GENERAL ORGANIZATION OF THE FUNCTIONAL ATLAS OF ORPHAN NUCLEAR
RECEPTORS RESEARCH PROGRAM (U19)
Development of a Functional Atlas of Orphan Nuclear Receptors requires
considerable effort to organize. A U19 application should be headed by
a Principal Investigator (PI), who is an expert in the field. As a
cooperative agreement, the primary governing body for the program will
be a Steering Committee, which will have responsibility for overall
study design and policy decisions (described in more detail under
“TERMS AND CONDITIONS OF AWARD”). Members of the Steering Committee
will include the PIs of research components and shared resources, and
key independently supported collaborators, as well as representative(s)
of the NIH.
Since the overall purpose of this initiative is to develop a Functional
Atlas of Orphan Nuclear Receptors, a Bioinformatics Resource will serve
as the focal point for the collaborative efforts, and will be a
required Shared Resource. This Bioinformatics Resource will be the
focal point for data collection and analysis, and serve as the primary
interface with the general research communit(ies)y. Research in the
form of individual projects (bridging and pilot) will be used to
acquire new information and fill in gaps, where needed.
In order to give structure to the collaborative arrangements inherent
in a U19, it is anticipated that at least two meetings/year of the
Steering Committee (study investigators and the NIDDK) will take place.
These meetings will commence once the Steering Committee has had an
initial organizational meeting at or near the time funding is
initiated. Applicants should formally state their willingness to
participate in such activities and plans for these meetings should be
included in the budget requests of the individual applications (see
below in TERMS AND CONDITIONS). The purpose of these meetings will be
to provide periodic updates on progress, resolve issues related to
sharing of resources and data, and modification (if necessary) of study
design and/or timetable, develop needs for additional expertise and
coverage through subcontracts, as well as development and entry of data
with the Bioinformatics Resource.
To promote the development of a collaborative program among the award
recipients, a number of issues need to be addressed in the application,
as discussed below. Applicants should discuss the rationale for their
individual and collaborative approaches, how they will interact
effectively with the Steering Committee and the Bioinformatics
Resource, and state their willingness to follow the common protocol
that will be agreed upon by the Steering Committee and that would apply
to all participants in the U19.
The U19 application should include elements of the following
categories:
RESEARCH COMPONENTS:
1. Bridging projects (e.g. Gene Expression, Tissue Specificity,
Physiology, Structure/Function) may be requested for
collaborative activities that would function as supplements to
the ongoing, funded, independent work in the laboratories of
participating investigators. These bridging projects to the
laboratories of participating investigators are to add to or
bridge the intellectual and technological approaches of the
collaborative program. They are not meant to be stand-alone
research efforts but are to be subprojects that tie (or enhance
the contribution of) the independent work of the participating
investigator to the large-scale collaborative program. These
bridging projects may be from 2-5 years in duration, as needed.
2. Pilot projects (e.g. Imaging, Ligand Discovery, Data Mining) may
be requested for investigators in an area deemed important to the
collaborative project, to add elements where gaps exist, or to
add investigators with critical knowledge or expertise. These
need not be from individuals having a research background in the
area of the collaborative program. These projects may not exceed
$75,000 in annual direct costs and must be limited to no more
than three such projects. Each project should be of sufficient
scope to qualify as an independent research effort. It is
primarily intended to allow the collaborative program to address
gaps in the overall scope, or to add investigators outside the
scientific mainstream of the project area in a mode that will
allow them to develop independent research in the area of the
collaborative program. While funding for an individual pilot may
run for three (3) years, at the discretion of the steering
committee, it is expected that the principal investigator of a
project will seek R01 funding during the period of the
collaborative project, based on the results obtained from the
project. Such R01 funding should include plans for further
interaction with other components of the Functional Atlas.
SHARED RESOURCES: The organizational structure of the collaborative
project may assume a variety of different forms, all focused on
addressing the scope described above. In addition to required
Bioinformatics and Administrative Resources, other Shared Resources may
be included, as needed (e.g., Transgenic Animals, Microarray,
Proteomics) to speed progress on the scientific goals of the project,
add additional capability to the collaborative project by bringing in
new or improved technology and/or by standardizing data among different
research teams among the collaborating or participating laboratories.
This might include such technologies as high-throughput gene chip
microarrays, imaging or transgenic methodologies. Other types of
resources might be for instrumentation, genomics, proteomics, high-
throughput assays, or computational/bioinformatics/modeling
capabilities not already provided by a Bioinformatics Resource. Any
such requests should be strongly justified in terms of contributions to
achieving the long-term goals of the Functional Atlas of Orphan Nuclear
Receptors, to increasing the synergy of the collaborative project, or
to enhancing overall cost effectiveness. The major focal point for
shared resources should be a Bioinformatics Resource, which will be
devoted to data collection, coordination, analysis, and to
dissemination of information developed by the various components of the
collaborative program. Each of the sub- and/or participating projects
should have plans for interfacing with this Bioinformatics Resource.
TERMS AND CONDITIONS OF AWARD
These special Terms of Award are in addition to and not in lieu of
otherwise applicable OMB administrative guidelines, HHS Grant
Administration Regulations at 45 CFR Parts 74 and 92, and other HHS,
PHS, and NIH Grant Administration policy statements.
1. Collaborative Responsibilities
The administrative and funding instrument used for this program is a
cooperative agreement (U19-Research Project), an "assistance" mechanism
(rather than an "acquisition" mechanism) in which substantial NIH
scientific and/or programmatic involvement with the awardee is
anticipated during performance of the activity. Under the cooperative
agreement, the NIDDK purpose is to support and/or stimulate the
recipient's activity by involvement in and otherwise working jointly
with the award recipient in a partnership role, but it is not to assume
direction, prime responsibility, or a dominant role in the activity.
Consistent with this concept, the dominant role and prime
responsibility for the activity resides with the awardee(s) for the
project as a whole, although specific tasks and activities in carrying
out the studies will be shared among the awardees and the NIDDK Program
Scientist.
2. Participating investigator:
A research project (U19) application will include a team of
investigators who will contribute to and benefit from participation
(collaboration) in the program. The members of the collaborative
project will be referred to collectively as participating
investigators, although one will be the Principal Investigator. It is
expected that each of the participating investigators will hold an
externally peer reviewed and funded research grant in the area of the
project, with the majority funded through regular research grants
supported by NIDDK, other NIH institutes and centers, and other
governmental and private agencies. Exceptions to the rule of external
funding may include participating investigators from industry, foreign
institutions or allied fields not traditionally supported by the NIH
(e.g., physics, computational biology, mathematics). Each participating
investigator must provide evidence of their commitment to the project
and a listing of organizational resources that will be committed to the
project.
Participating investigators will work together via the Steering
Committee to develop workable guidelines for achieving the objectives
of the collaborative program. Participating investigators must agree
to abide by the policies and rules set up for the collaborative program
and to the terms and conditions described in this document to be
eligible to participate. During the period of the award, a
participating investigator whose independent research support
terminates may continue as a participating investigator at the
discretion of the Steering Committee and with the approval of the NIDDK
Program Scientist. Funds from this award are not to be used to support
the independent project of such an investigator. It is expected that
new participating investigators will be added to the collaborative
project over the period of the award as deemed appropriate by the
principal investigator and steering committee and with the approval of
the NIDDK Program Scientist; these additions will be reported in the
annual progress report.
3. Awardee Rights and Responsibilities:
The PI, and participating investigators, will have primary authority
and responsibility to define objectives and approaches, and to plan,
conduct, analyze, and publish results, interpretations, and conclusions
of studies conducted under the terms and conditions of the cooperative
agreement award.
The PI will assume responsibility and accountability to the applicant
organization officials and to the NIDDK for the performance and proper
conduct of the research supported by the project in accordance with the
terms and conditions of the award.
The PI and one participating investigator from each participating
project of the program will participate as permanent, voting members of
the Steering Committee (see below), will attend the initial Planning
Meeting and any subsequent Steering Committee meetings in the first and
subsequent years, as needed.
The PI will be responsible for contributing to and implementing the
goals, priorities, procedures, and policies agreed upon by the Steering
Committee, and will be responsible for close coordination and
cooperation with other of the Functional Atlas of Orphan Nuclear
Receptors program and NIDDK staff.
Awardees will retain custody of, and have primary rights to, the data
developed under these awards, subject to Government rights of access
consistent with current HHS, PHS, and NIH policies. Investigators
conducting biomedical research frequently develop unique research
resources. The policy of the PHS is to make available to the public
the results and accomplishments of the activities that it funds.
Principles and guidelines for recipients of NIH research grants on
obtaining and disseminating biomedical research resources can be found
at: http://www.nih.gov/od/ott/RTguide.
The NIDDK reserves the right to require the transfer of animals,
reagents, and pertinent data that are generated as the result of
participation in research supported under these awards to an eligible
third party, in order to preserve the continuity of the research
project. Third parties supported under these awards must be informed
of this right.
The Functional Atlas group will be expected to provide the NIDDK and
the NIA with data in a uniform, usable platform throughout the course
of the studies and after the termination of the studies supported by
this RFA.
Effective conduct of Functional Atlas goals, as defined in this RFA and
following Steering Committee action, will require considerable
electronic communication of data and other information among the
Functional Atlas and between the various constituent components and the
NIDDK. The Functional Atlas members will be required to demonstrate
that they have the ability to transfer data accurately and effectively.
4. NIDDK Staff Responsibilities
The NIDDK Program Scientist will have substantial scientific-
programmatic involvement during conduct of this activity, through
technical assistance, advice and coordination above and beyond normal
program stewardship for grants, as described below. The dominant role
and prime responsibility for the activity resides with the awardees for
the project as a whole, although specific tasks and activities in
carrying out the studies will be shared among the awardees and the
NIDDK Program Scientist.
The NIDDK Program Scientist will have voting membership on the Steering
Committee and, as determined by that committee, its subcommittees; will
coordinate and facilitate the Functional Atlas programs, attend and
participate as a voting member in all meetings of the Functional Atlas
Steering Committee, and provide liaison between the Steering Committee,
the Functional Atlas investigators, and the NIDDK.
The NIDDK Program Scientist and the NIDDK will ensure that there is an
effective, Internet-based mechanism to enable electronic communication
among the Functional Atlas, and with the NIH.
The NIDDK Program Scientist will assist the Steering Committee in
developing and drafting operating policies and policies for dealing
with recurring situations that require coordinated action.
Since the NIDDK Program Scientist will be a participating member of the
Steering Committee, to avoid any conflicts of interest, a separate
NIDDK Project Officer will have responsibility for the analysis,
review, and approval of all budgetary actions. This Project Officer
will be separate and distinct from the NIDDK Program Scientist, and
will not be a member of the steering committee.
NIDDK and NIH extramural staff with relevant scientific expertise, or
who manage research grant programs that relate scientifically to the
goals of the Functional Atlas program, will form a separate NIDDK
Functional Atlas Working Group. The Group will meet regularly to review
the progress of the Functional Atlas, and to advise the NIDDK Program
Scientist of scientific developments and opportunities that may enhance
the achievement of the goals.
The NIDDK Functional Atlas Working Group will collaborate with the
NIDDK Program Scientist to organize and implement the workshops and
symposia recommended by the Functional Atlas Steering Committee, and to
provide a liaison between the appropriate research communit(ies)y and
the members of the Functional Atlas, as well as the External Scientific
Working Group.
The NIDDK reserves the right to terminate or curtail the study (or an
individual award) in the event of a major breach in the protocol or
substantial changes in the agreed-upon protocol with which the
Institute does not agree.
5. Governance
A Steering Committee, composed of the Project PI, the participating
project principal investigator(s), and the NIDDK Program Scientist will
be the main governing board of the study and will have primary
responsibility for developing common research designs, protocols and
manuals, facilitating the conduct and monitoring of studies, reporting
study results, and resolving issues that may arise. The principal
investigators from the participating projects, any relevant subcontract
projects, and the Bioinformatics Resource, and the NIDDK Program
Scientist will each have one vote. The chairperson, who will be
someone other than an NIDDK staff member, will be selected by the
Steering Committee. Subcommittees will be established by the Steering
Committee, as appropriate; the Program Scientist will serve on
subcommittees, as he/she deems appropriate. The collaborative protocols
will be developed by the Steering Committee. Data will be reviewed and
submitted centrally to the Bioinformatics Resource. Protocols will
define rules regarding access to data and publications, as well as
ensuring rapid dissemination of data to the general research community.
It is anticipated that awardees will have lead responsibilities in all
joint tasks and activities, as assisted by the NIDDK Program Scientist,
where appropriate. Awardees will be required to accept and implement
the common protocol and procedures approved by the Steering Committee.
6. Arbitration
Any disagreement that may arise on scientific/programmatic matters
(within the scope of the award), between award recipients and the
Institute may be brought to arbitration. An arbitration panel will be
composed of three members: one selected by the Steering Committee (with
the NIDDK member not voting) or by the individual awardee in the event
of an individual disagreement, a second member selected by NIDDK, and
the third member selected by the two prior selected members. This
special arbitration procedure in no way affects the awardee's right to
appeal an adverse action that is otherwise appealable in accordance
with the PHS regulations at 42 CFR Part 50, Subpart D and HHS
regulation at 45 CFR Part 16.
INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS
It is the policy of the NIH that women and members of minority groups
and their sub- populations must be included in all NIH-supported
biomedical and behavioral research projects involving human subjects,
unless a clear and compelling rationale and justification is provided
indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of
the research. This policy results from the NIH Revitalization Act of
1993 (Section 492B of Public Law 103-43).
All investigators proposing research involving human subjects should
read the UPDATED "NIH Guidelines for Inclusion of Women and Minorities
as Subjects in Clinical Research," published in the NIH Guide for
Grants and Contracts on August 2, 2000:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-048.html.
A completed copy of the updated Guidelines is available at:
http://grants.nih.gov/grants/funding/women_min/guidelines_update.htm.
The revisions relate to NIH defined Phase III clinical trials and
require: a) all applications or proposals and/or protocols to provide a
description of plans to conduct analyses, as appropriate, to address
differences by sex/gender and/or racial/ethnic groups, including
subgroups, if applicable; and b) all investigators to report accrual,
and to conduct and report analyses, as appropriate, by sex/gender
and/or racial/ethnic group differences.
INCLUSION OF CHILDREN AS PARTICIPANTS IN RESEARCH INVOLVING HUMAN
SUBJECTS
It is the policy of NIH that children (i.e., individuals under the age
of 21) must be included in all human subjects research conducted or
supported by the NIH, unless there are scientific and ethical reasons
not to include them. This policy applies to all initial (Type 1)
applications submitted for receipt dates after October 1, 1998.
All investigators proposing research involving human subjects should
read the "NIH Policy and Guidelines" on the Inclusion of Children as
Participants in Research Involving Human Subjects that was published in
the NIH Guide for Grants and Contracts, March 6, 1998, and is available
at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html.
Investigators also may obtain copies of these policies from the program
staff listed under INQUIRIES. Program staff may also provide
additional relevant information concerning the policy.
REQUIRED EDUCATION IN THE PROTECTION OF HUMAN RESEARCH PARTICIPANTS
All investigators proposing research involving human subjects should
read the policy that was published in the NIH Guide for Grants an
Contracts, June 5, 2000 (Revised August 25, 2000), and is available at
the following URL address
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
GUIDELINES FOR RESEARCH USING HUMAN PLURIPOTENT STEM CELLS
At the present time, the NIH cannot fund research involving the use of
stem cells derived from human embryos.. This restriction does not apply
to: human adult stem cell research; derivation or use of pluripotent
stem cells from human fetal tissue; or animal stem cell research. For
the most current information on policies related to research using
human pluripotent stem cells, investigators should access the National
Institutes of Health Stem Cell Information site at:
http://stemcells.nih.gov/index.asp
Details on the approval process and the procedures for submitting the
required documentation of compliance are at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-050.html
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. Reviewers are cautioned that
their anonymity may be compromised when they directly access an
Internet site.
LETTER OF INTENT
Prospective applicants are asked to submit, by October 17, 2001 a
letter of intent that includes a descriptive title of the proposed
research; name, address, and telephone number of the Principal
Investigator; identities of other key personnel and participating
institutions; and the number and title of the RFA in response to which
the application may be submitted.
Although a letter of intent is not required, is not binding, and does
not enter into the review of subsequent applications, the information
allows NIDDK staff to estimate the potential review workload and to
plan the review.
The Letter of Intent is to be sent to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes
and Digestive and Kidney Diseases
6707 Democracy Blvd
Room 752, MSC 5452
Bethesda, MD 20892
(For Fed Ex and UPS use 20817)
301-594-8897
301-480-3505 fax
FC15Y@NIH.GOV
APPLICATION PROCEDURES
U19 application should demonstrate essential elements of unity and
interdependence that, through the collaborative effort, result in a
greater contribution to program goals, as defined in the objectives for
the Functional Atlas, than would occur if each project were pursued
individually. Specifically, the relationship and contributions of each
Research Component and Shared Resource to the goals of the Functional
Atlas of Orphan Nuclear Receptors should be discussed. These programs
provide support for research projects as well as shared resources and
facilities, which are available to individual projects comprising the
program. Shared Resources must provide essential functions, services,
techniques, determinations or instrumentation that will enhance at
least 2 individual research projects. A Bioinformatics Resource is
required. In this component, details as to how data that are generated
from individual projects will be stored, organized, analyzed, or
visualized should be described. An Administrative Resource is required
to assist in allocation of resources, coordination of projects, provide
logistical support for meetings and workshops, and coordination with
subcontracts. Subcontract budgets should be listed on a separate page,
and the subcontract Facilities and Administrative (F&A) costs should be
calculated and listed in the usual place as part of the direct costs of
the budget (see “TABLE OF CONTENTS”).
Preparation of Application
Applications are to be submitted on the standard research grant
application form PHS 398 (rev. 4/98). Application kits are available
at most institutional offices of sponsored research and may be obtained
from the Division of Extramural Outreach and Information Resources,
National Institutes of Health, 6701 Rockledge Drive, MSC 7910,
Bethesda, MD 20892-7910, telephone (301) 435-0714, email:
grantinfo@nih.gov and on the Internet at:
http://grants.nih.gov/grants/funding/phs398/phs398.html.
A response to this RFA should consist of an application that, in
addition to or in lieu of part of the items requested in the PHS 398
(http://grants.nih.gov/grants/funding/phs398/phs398.html), includes:
Description, Performance Site(s), and Key Personnel: On page 2,
describe briefly the proposed large scale-collaborative research
project (Abstract). List all key personnel involved in the
collaborative project; use a continuation page if needed.
Table of Contents. Prepare a Table of Contents for the overall project
that includes the items listed below. Page limitations are given in the
specific descriptions for each section.
SAMPLE TABLE OF CONTENTS
SECTION I
Face Page
Table of Contents (Overall program)
Detailed Budget for First 12-Month Period
Budget Estimate for Each Year of Project
Summary of All Other Sources of Support
Biographical Sketches (PI and all participating investigators, key
personnel and collaborators)
SECTION II
Overall Program
Goals
Research Plan
Program Summary
Administrative Management Plan
Project Management Plan
Preliminary Studies
Plan for Data Sharing and Intellectual Property
Institutional Environment and Resources
Organization and Administrative Structure
SECTION III
Shared Resources
Shared Resource A
Title Page (Title, Resource Director)
Description of Resource
Budget for the First 12-Month Period
Budget Estimate for Each Year of Requested Support
Role and Justification for the Shared Resource
Plan of operation
Integration with the program
Gender and Minority Inclusion
Children Inclusion
Human Subjects
Vertebrate Animals
Consortium/Contractual Arrangements
Consultants/Collaborators
Shared Resource B, etc
Title Page (Title, Resource Director)
Description of Resource
Etc.
SECTION IV.
Research Components
Bridging Project 1
Title Page (Title, Project Leader)
Description of Research Plan/List of Key Personnel
Detailed Budget for First 12-Month Period
Budget Estimate for Each Year of Requested Support
Resources and Environment
Research Plan
Plan for integration with overall program
Gender and Minority Inclusion
Children Inclusion
Human Subjects
Vertebrate Animals
Consortium/Contractual Arrangements
Consultants/Collaborators
Bridging Project 2, etc.
Title Page (Title, Project Leader)
Etc.
Pilot Projects (up to 3)
Title Page (Project 1, 2, etc)
Detailed Budget for First 12-Month Period
Budget Estimate for Each Year of Requested Support
Resources and Environment
Research Plan
Plan for integration with overall program
Gender and Minority Inclusion
Children Inclusion
Human Subjects
Vertebrate Animals
Consortium/Contractual Arrangements
Consultants/Collaborators
Literature Cited with complete titles and authors for the entire
program.
Checklist
The major areas to be listed in the Table of Contents above, appear
below in capital letters.
BUDGET ESTIMATES: Specific examples of allowable costs that may be
requested include:
In addition to the overall budget for the entire Functional Atlas
program, include a separate budget for each bridging project, the (up
to 3) pilot projects and the Shared Resources. Applications for U19-
Research Project awards may not request more than $3.0 million in
annual total costs (exclusive of subcontract F&A costs requested as a
direct cost by the applicant organization) for any year of the award.
Salaries for support personnel required for coordination and
maintenance of the program, such as secretaries or administrative
assistants, may also be included, as necessary, in the Administrative
Resource.
Specific Items that may be included:
1. Salaries for the principal investigator, members of the steering
committee, participating investigators, technical, and support
personnel commensurate with their level of effort in the large-scale
collaborative program.
2. Pilot projects to investigators relevant to the Functional Atlas can
be without current independent research support in the area. Pilots
must not exceed $75,000 in annual direct costs and must be limited to
no more than three such projects per application. They may include
travel of personnel (e.g. predoctoral students, postdoctoral trainees,
and investigators) to different laboratories to gain specialized
expertise. These grants may be for no more than 3 years each, and may
be replaced by such new projects as the Steering Committee deems
appropriate to achieve the goals of the overall program (see Project
Management Plan). The Pilot and Feasibility projects should be listed
with a common budget, each project not to exceed the individual cap of
$75,000.
3. Travel to and conduct of regular meetings of the steering committee
and regular meetings of the participating investigators.
4. Shared Resource facilities (examples: instrumentation, genomics,
proteomics, model organism, high-throughput assay, or
computational/bioinformatics).
5. Electronic media resources to allow participation of off-site
laboratories and/or the means necessary to establish collaboratory
capabilities and for information dissemination. Travel to and conduct
of regular meetings of an external advisory working group.
Composite budget. Use Form Page 4, "DETAILED BUDGET FOR INITIAL BUDGET
PERIOD," of Form PHS-398 to present the total budget for all requested
support for the first year. For each category such as "Personnel,"
Equipment," etc., give the amount requested for each Resource unit and
each component project, with subtotals. For consortium arrangements
involving other institutions or organizations, include total (direct
and facilities and administration) costs
associated with such third-party participation in the
"Consortium/Contractual Costs" category. Note that consortium costs
will count against the $3.0 Million Total Costs cap. Costs for
purchased services should be itemized under "Other Expenses."
Use Form Page 5, "BUDGET FOR ENTIRE PROPOSED PROJECT PERIOD," of Form
PHS-398 to prepare a budget, by category, that provides totals for each
year of requested support. The costs for the Pilot and Feasibility
studies should be reported as one total figure for the (up to) three
such projects. Requests for any increases in succeeding years must be
justified in the individual component subprojects (bridging projects
and pilot projects) and Resource budgets.
Individual budgets for shared resource and research components: For the
first year budgets of each of the shared resource and research
projects, use Form Page 4 of the PHS-398. Use Form Page 5 of the PHS-
398 to report the budgets of each of the projects and shared resources
for total project period (years 02-05).
Budget justifications and explanations: Describe the specific
functions of all key personnel, including consultants, collaborators,
and technical staff. Provide justifications for requested equipment.
For years 02-05 of the application, justify any significant increases
or decreases in any category over the first year budget. Applicants
must budget for travel and per diem that will allow the Principal
Investigator, and designated participating or senior investigator to
participate in at least two steering committee meetings each year.
Applicants should plan to attend a workshop or symposium every year in
years 2-5.
BIOGRAPHICAL SKETCHES AND LETTERS OF COMMITMENT: Biographical sketches
and letters of commitment must be included from all participating
investigators indicating their willingness to follow guidelines and
procedures established for the large-scale collaborative project. The
format described in the PHS398 application for modular applications
should be followed for this information.
RESOURCES AND ENVIRONMENT: Complete the "Resources" page of PHS-398
for the overall large-scale collaborative project, including both the
host institution and any participating institutions. Briefly describe
the features of the institutional environment(s) that are relevant to
the effective implementation of the proposed program. As appropriate,
describe available resources, such as clinical and laboratory
facilities, participating and affiliated units, patient populations,
geographical distribution of space and personnel, and consultative
resources.
RESEARCH PLAN
In the PHS398 application kit a 25 page limit for the Research Plan is
described. In lieu of that limitation, for the Functional Atlas, a
forty (40) page limit is in effect for the following four sections
(PROGRAM SUMMARY, ADMINISTRATIVE MANAGEMENT PLAN, PROJECT MANAGEMENT
PLAN, and PRELIMINARY STUDIES). Investigators should endeavor to be
concise. For other sections please follow the instructions for each
individual part of the application, as below.
PROGRAM SUMMARY: A summary describing the goals and operation of the
program. Explain how the scope of this initiative will be addressed
and how the approach of using a large-scale collaborative agreement is
critical to its solution. Discuss the range of scientific expertise to
be brought to bear on the research problem. Explain the interactions
that will occur between investigators at the host site and at the
participating sites. Explain how each element of the large-scale
collaborative project will contribute to successful attainment of its
goals. Explain the programmatic value of the Shared Resources, and the
Research Components (bridging and pilot projects). Explain how the
information resulting from the collaborative efforts of the entire
program, to include the laboratories of the participating
investigators, will be integrated into the Bioinformatics Resource and
with comprehensive program, as a whole. Discuss how information
generated by the collaborative program will be disseminated to the
scientific community, in general.
ADMINISTRATIVE MANAGEMENT PLAN: Describe the structure, organization,
and operation of the program. Describe the organizational framework and
provide an organizational chart detailing the flow of information
within the collaborative program. Discuss arrangements between the
collaborating institutions that are important to effective operation of
the U19. Detail the usage of the Shared Resources by the participating
investigators. Include any outreach efforts to provide access to the
Shared Resource to investigators outside the collaborative program.
Discuss how the views of the scientific community impacted by the
collaborative program will be considered.
PROJECT MANAGEMENT PLAN: Provide a timeline for the program, as a
whole, and for each component, defining yearly landmarks to be used to
assess progress. Explain how progress in the bridging and pilot
projects and efficiency of the Shared Resources will be tracked.
Include an evaluation plan to determine how the collaborative program
is progressing. Discuss the plan for evolving landmarks. Explain how
the External Scientific Working Group will be used in updating the
project management plan. Explain how decisions will be made to
add/delete participating investigators and to respond to changes in
short term goals that research findings will make necessary. Provide a
plan for assessment of the bridging and pilot studies with emphasis on
how it will be decided what duration they should have and whether and
how they should be replaced.
PRELIMINARY STUDIES: Provide any preliminary studies/data that may be
relevant to the overall program. Data should be in a readily
interpretable form, with legends and appropriate identification of
figures/tables in the text.
Specific page limitations have been established for the following
sections:
PLAN FOR DATA SHARING AND INTELLECTUAL PROPERTY (two page limit): The
principal investigator and steering committee should (1) propose a plan
for providing access to the data and information generated by the
large-scale collaborative project to the members of the project and the
scientific public; (2) address if or how intellectual property rights
will be exercised; (3) discuss guidelines for licensing of joint
inventions; (4) discuss procedures for settling of intellectual
property disputes; (5) discuss the existence of any pre-existing
intellectual property rights, including options to for-profit research
sponsors; and (6) propose a plan for disseminating the technologies,
assays, and associated reagents developed under this RFA
INSTITUTIONAL ENVIRONMENT AND RESOURCES (two page limit): The
environment and resources at the host institution that will be
available to this program should be described. The environment and
resources available at collaborating institutions should be provided in
the descriptions of those specific projects.
SHARED RESOURCES
SHARED RESOURCE A. BIOINFORMATICS RESOURCE (required; ten page limit):
This Resource will be required for data accumulation, analysis,
coordination and dissemination. Dissemination of information on
techniques, scientific findings, and methodologies is a vital component
of the large-scale collaborative program. Effective use of computer
technology, print media, and telecommunications are relevant. Describe
the staffing (including a Resource Director, as well as any
professional or technical personnel and their duties), facilities, and
resources that will be devoted to this goal. Indicate plans to make
results of research or other unique features of the collaborative
project available for as wide an audience as possible. Describe how
data generated by the Shared Resource and Research Components will be
processed into the information to be disseminated. Discuss how data
will be reviewed prior to inclusion in the bioinformatics database.
Discuss plans for dissemination of published and unpublished data.
SHARED RESOURCE B. ADMINISTRATIVE RESOURCE (required; five page
limit): This Resource must be directed by the principal investigator.
Include the objectives of the Resource, a description of its staffing
and services to be provided to other resources and to the participating
investigators. Communicating the objectives of the collaborative
program and fostering opportunities for collaboration are encouraged.
Expenses associated with the operation of the steering committee,
meetings of all or subgroups of the participating investigators, and
meetings and operation of the External Scientific Working Group would
fall under the Administrative Resource.
SHARED RESOURCE C (and others): There is a 10 page limit per Resource.
Provide specific titles for any proposed scientific Shared Resources
(e.g., instrumentation; genomics; proteomics; model organism; high-
throughput assay; or computational, modeling, or bioinformatics), along
with a designated Resource Director who possesses expertise in the area
of each Resource. Describe the professional and technical staff to be
involved in the Resource(s), and their duties. Include plans to
utilize the Resource(s), including services that will be provided, and
to whom, and their bearing on productivity and quality of the
collaborative research effort.
RESEARCH COMPONENTS
BRIDGING PROJECTS (ten page limit for each bridging project): A
bridging project should be designed to support work in the laboratory
of a participating investigator relevant to the objectives of the
overall program. For all proposed projects, the underlying rationale
and potential impact of the studies should be specifically addressed.
The need for the bridging project to tie (or enhance) the independent
work of the participating investigator to the goals of the
collaborative program must be described. Essential information for the
research plan should include specific aims, background and
significance, preliminary studies, and research design and methods, and
may be presented as a combined summary of these sections emphasizing
the following:
Describe the new research proposed in the bridging project and explain
how this work more fully integrates the participating investigator’s
independently supported work into the overall theme and objectives of
this collaborative Research Program. A bridging project should extend
the participating investigator’s independent work in a direction(s)
relevant to goals of the Functional Atlas program. A bridging project
to do more of what the investigator is already doing should be
considered only if there are extraordinary circumstances that make it
essential for the effective functioning of the large-scale project. If
the participating investigator’s work is already closely tied to the
large-scale project, a bridging project should not be needed.
Substantial new research projects should not be submitted for bridging
projects; these should be submitted as regular R01 applications, even
if they add value to the large-scale project.
Projects must be described in sufficient detail to permit evaluation
through the competitive peer-review process. For each bridging project
undertaken as part of the collaborative program, also to be included
are sections (where appropriate) that address: Gender and Minority
Inclusion for Research Involving Human Subjects, Inclusion of Children
as Participants in Research Involving Human Subjects, Human Subjects,
Vertebrate Animals, Consortium/Contractual Arrangements, Consultants.
Literature Cited should be included in the citations for the entire
program, at the end of the application.
PILOT PROJECTS (five page limit for each pilot project for the research
plan: specific aims, background and significance, preliminary studies,
and research design and methods; maximum of three pilot projects per
large scale collaborative program): Pilot projects may support the work
of investigators not already supported in the area of the collaborative
program but who have unique skills or expertise that add to the
collaborative effort. For all proposed projects, the underlying
rationale and potential impact of the studies should be specifically
addressed. How the pilot project will add new elements essential to
achieving the goals of the collaborative program must be described.
Projects must be described in sufficient detail to permit evaluation
through the competitive peer-review process. For each pilot project
undertaken as part of the collaborative project, include the following
sections: Abstract (one paragraph), Specific Aims, Background and
Significance, Preliminary Studies, Research Design and Methods, as well
as Gender and Minority Inclusion for Research Involving Human Subjects,
Inclusion of Children as Participants in Research Involving Human
Subjects, Human Subjects, Vertebrate Animals, Consortium/Contractual
Arrangements, Consultants. Literature Cited should be included in the
citations for the entire program, at the end of the application.
INSTITUTIONAL COMMITMENTS: Letters signed by authorized business
officials of each of the participating investigators' institutions
committing support to the large-scale collaborative project must be
included. Applicants for proposals that include consortium
arrangements should refer to the NIH Grants Policy Statement appendix
on consortium arrangements at:
http://grants.nih.gov/grants/policy/nihgps/part_iii_5.htm#Consortium.
OTHER SUPPORT OF PARTICIPATING INVESTIGATORS: For the principal
investigator, steering committee members, participating investigators,
and heads of Resource resources, provide a listing of all other support
for each participant in the usual NIH format for non-modular
applications
(see http://grants.nih.gov/grants/funding/phs398/phs398.html); support
for other investigators such as postdoctoral students should not be
listed. For the relevant grant support that allows participating
investigators to be part of the large-scale collaborative project,
provide the specific aims of the project and describe in sufficient
detail for evaluation the relationship of the funded grant to the goals
of the proposed collaborative Research Program (U19).
METHOD OF APPLYING
The RFA label available in the PHS 398 (rev. 4/98) application form
must be affixed to the bottom of the face page of applications.
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. Enter the RFA number on the label. 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 sample RFA label available at:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been
modified to allow for this change. Please note this is in pdf format.
Submit a signed, typewritten original of the application, including the
Checklist, and three signed, exact 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 and
all five sets of any appendix material must be sent to:
Francisco O. Calvo, Ph.D.
Chief, Review Branch
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Blvd, Room 752
Bethesda, MD 20892-5452
Applications must be received by November 19, 2001. If an application
is received after the due 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.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by CSR and
responsiveness by the NIDDK. 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 the NIDDK in accordance with the review
criteria stated below.
As part of the initial merit review, a process may be used by the
initial review group in which applications receive a written critique
and 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, assigned a priority
score, and receive a second level review by the National Diabetes and
Digestive and Kidney Diseases Advisory Council.
NIH Review Criteria for Investigator-initiated projects:
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
In the written comments, reviewer will be asked to discuss the
following aspects of the application 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 the 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.
In addition to the criteria below, in accordance with NIH policy, all
applications will also be reviewed with respect to the following (where
relevant):
o Adequacy of plans to include both genders, minorities and their
subgroups, and children as appropriate for the scientific goals
of the research. Plans for the recruitment and retention of
subjects will also be evaluated.
o The reasonableness of the proposed budget and duration to the
proposed research.
o The adequacy of the proposed protection of humans, animals, or
the environment, to the extent that they may be adversely
affected by the project proposed in the application.
o For applications with foreign components: Availability of special
opportunities for furthering research programs through the use of
unusual talent resources, populations, or environmental
conditions in other countries which are not readily available in
the United States or which provide augmentation of existing U.S.
resources.
REVIEW CRITERIA FOR THE RESEARCH PROJECT-COOPERATIVE AGREEMENT (U19)
Overall Project
1. Significance. Does this collaborative Research Program adequately
address the central question of this initiative, i.e. development of a
Functional Atlas of Orphan Nuclear Receptors, in a way that would be
difficult to address by separate grants? Do the arrangements for data
sharing maximize the impact of the collaborative program?
2. Approach. Are the conceptual framework, design, methods, and
analyses adequately developed, well integrated, and appropriate to the
scientific aims of the collaborative program? Is the project
management plan adequate and comprehensive? Is the administrative
framework appropriate and designed to integrate the various components?
Do landmarks articulate key indicators set for appropriate times that
will demonstrate significant forward progress for the collaborative
program? Are the plans to monitor and evaluate progress of the
collaborative program adequate? Will the Bioinformatics Resource
support the objectives of the Functional Atlas? Are the plans to share
the data and findings with the larger community adequate? How will the
group take the views of the scientific community impacted by the large-
scale collaborative program into consideration?
3. Innovation. Will the collaborative program challenge existing
paradigms or develop new methodologies or technologies? Will the
collaborative program attack the problem in a significantly new way?
What will be the value added over individual grants?
4. Investigators. Is the principal investigator's major research
activity within the research area of the collaborative program? Is the
principal investigator well suited to the scientific and administrative
leadership required to carry out this work? Is the level of effort
proposed for the principal investigator and the members of the steering
committee appropriate? Is the work proposed appropriate to the
experience level of the collaborative program's research and technical
staff? Are the research grants of the participating investigators
within the area of the collaborative program? Are the participating
investigators well chosen for their roles in the collaborative program?
Is the plan to add and delete participating investigators to and from
the collaborative program satisfactory?
5. Environment. Will the proposed collaborative program take
advantage of unique features of the scientific environments of the
component projects? Is the level of institutional support adequate?
Are the requested Shared Resource facilities critical to achieving the
scientific goals of the collaborative program; are they cost effective?
Is access to the Shared Resource facilities appropriate?
In addition, the following criteria will be considered for merit
review: The commitment to the program by the principal investigator and
the members of the steering committee will be a consideration. For
applications that are multi-institutional or that involve industry, the
adequacy of plans to resolve intellectual property issues will be a
consideration. The commitment of the host and participating
universities to supporting the large scale collaborative program will
also be considered: this would be reflected in efforts to work out
ahead of time potential intellectual property issues and to remove any
institutional barriers to the establishment and healthy maintenance of
the collaborative program.
Review Criteria for Research Components (Bridging and Pilot Projects)
1. Significance. Does this project address an important problem
relevant to the overall scope of the Functional Atlas? If the aims of
the application are achieved, how will scientific knowledge be
advanced? What will be the effect of these studies on the achieving the
goals of the collaborative program? Will the bridging project tie or
enhance the independent work of the participating investigator to the
collaborative program, or will the pilot project add an essential
missing aspect to the collaborative program?
2. Approach. Are the conceptual framework, design, methods, and
analyses adequately developed, well-integrated, and appropriate to the
aims of the program?
3. Innovation. Does the collaborative nature of the project enhance
potential innovation?
4. Investigator. Is the participating investigator appropriately
trained and well suited to carry out a collaborative project? Is the
work proposed appropriate to the experience level of the participating
investigator and other researchers (if any)?
5.Environment. Does the scientific environment in which the work will
be done contribute to the probability of success? Do the proposed
experiments take advantage of unique features of the scientific
environment or employ useful collaborative arrangements?
Review Criteria for Shared Resources.
1. Facilities within the Shared Resource compared to the state of the
art; the contributions of the Shared Resources to fulfilling the goals
of collaborative program.
2. The extent to which Shared Resource units promote greater
collaboration and cohesiveness among the participating investigators.
Does this resource promote an economy of scale? Are there unique
aspects of the resource that contribute to achieving the overall goals
of the program?
3. Qualifications, experience, and commitment to the large-scale
collaborative program mission of the investigators responsible for the
Shared Resources and their abilities to devote the required time and
effort to the program.
4. Appropriateness of the budgetary requests.
AWARD CRITERIA
Award criteria that will be used to make funding decisions include:
o scientific merit (as determined by peer review)
o program priorities
o program balance
o availability of funds
SCHEDULE
Application Receipt Date: November 19, 2001
Peer Review Date: Feb.-March 2002
Advisory Council Date: May 2002
Earliest Anticipated Award Date: September 30, 2002
INQUIRIES
Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.
Direct inquiries regarding programmatic issues relevant to NIDDK to:
Ronald Margolis, Ph.D.
Senior Advisor, Molecular Endocrinology
Division of Diabetes, Endocrinology, and Metabolism
National Institute of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 6107 MSC 5460
Bethesda, MD 20892-5460
Telephone: (301) 594-8819
FAX: 301-435-6047
E-mail: rm76f@nih.gov
Direct inquiries regarding fiscal matters to:
Cheryl Chick
Division of Extramural Activities
NIDDK
6707 Democracy Boulevard, Rm. 714 MSC 5460
Bethesda, MD 20892-5460
Telephone: (301) 594-8825
FAX: 301-480-3504
E-mail: cc149o@nih.gov
Direct inquiries regarding programmatic issues relevant to NIA to:
Frank Bellino, Ph.D.
Biology of Aging Program
National Institute on Aging
7201 Wisconsin Avenue, Suite 2C231 MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-6402
FAX: (301) 402-0010
Email: FB12A@nih.gov
Direct inquiries regarding fiscal matters to:
Linda Whipp
Grants and Contracts Management Office
National Institute on Aging
7201 Wisconsin Avenue, Suite 2N212, MSC 9205
Bethesda, MD 20892-9205
Telephone: (301) 496-1472
FAX: (301) 402-3672
Email: lw17m@nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance
No. 93.847 for DEM (NIDDK), and No. 93.866 (NIA). Awards are made
under authorization of the Public Health Service Act, Title IV, Part A
(Public Law 78-410, as amended by Public Law 99-158, 42 USC 241 and
285) and administered under NIH grants policies and Federal Regulations
42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to
the intergovernmental review requirements of Executive Order 12372 or
Health Systems Agency review.
The PHS strongly encourages all grant and contract recipients to
provide a smoke-free workplace and promote the non-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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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Office of Extramural Research (OER) |
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National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892 |
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Department of Health and Human Services (HHS) |
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