COMPREHENSIVE PROGRAMS IN BETA CELL BIOLOGY
Release Date: August 14, 2001
RFA: RFA-DK-02-014
National Institute of Diabetes and Digestive and Kidney Diseases
(http://www.niddk.nih.gov/)
Letter of Intent Receipt Date: February 13, 2002
Application Receipt Date: March 13, 2002
PURPOSE
The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
is seeking to intensify investigator-initiated collaborative research aimed
at understanding the signaling pathways in the adult pancreatic beta cell,
and how these signaling networks are integrated by the different cell types
of the pancreatic islet. This initiative is intended to support large multi-
component projects of outstanding investigators with innovative, high impact
studies focused on the beta cell and the adult pancreatic islet; to attract
established investigators who can bring novel or advanced techniques, tools
and concepts from other areas of research to the study of beta cell biology;
and to foster interdisciplinary approaches to the study of beta cell biology.
Use of emerging genomic and proteomic methods to elucidate beta cell specific
trafficking events, signaling pathways, and novel components of the islet
microenvironment required for proper beta cell function is strongly
encouraged. The ultimate goal is to use this increased understanding of the
biology of the pancreatic islet to develop novel approaches to the treatment
of diabetes. In further support of this initiative, the NIDDK will hold a
workshop, “Beta Cell Biology in the 21st Century: Engineering a Pathway to
Greater Understanding”, on November 26-28. An important goal of this
workshop is to identify areas of research opportunity in the adult pancreatic
beta cell. Prospective applicants to this RFA are encouraged to attend this
important workshop http://www.betacellbiology.niddk.nih.gov.
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 Request for
Applications (RFA), COMPREHENSIVE PROGRAMS IN BETA CELL BIOLOGY, 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
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic and foreign, 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 (PI).
MECHANISM OF SUPPORT
This RFA will use the National Institutes of Health (NIH) R01 award mechanism
to support a full range of applications as outlined below. Responsibility
for the planning, direction, and execution of the proposed project will be
solely that of the applicant. The total project period for an application
submitted in response to this RFA may not exceed 5 years. This RFA is a one-
time solicitation. Future unsolicited competing continuation applications
will compete with all investigator-initiated applications and be reviewed
according to the customary peer review procedures. The anticipated award
date is September 30, 2002.
The R01 mechanism is highly flexible and can be used to accommodate a range
of project sizes and organizational structures. In this initiative, the
NIDDK is encouraging the formation of collaborations among scientists with a
variety of different expertise and ideas, so that multifaceted approaches,
diverse skills, unique tools, and special resources can be used to
investigate the biology of the adult beta cell. Numerous organizational
structures are possible. For example, the R01 can be used for large projects
in which all the work is coordinated by a single PI, and collaborating
projects are located at a single institution.
When collaborating investigators are at different institutions, but the
project is to be conducted under the auspices of a single PI, a large R01
with several subcontracts may be requested. This allows for integration of
multi-disciplinary approaches and a variety of resources under the direction
of one PI. With this scenario, the PI is responsible for ensuring that the
scientific goals are met, and for resource allocation. Furthermore, short-
term high-risk potentially high pay off studies, as well as studies aimed at
the development of novel technologies or reagents can be submitted as part of
a larger project.
When a project is better served by an organizational structure where several
senior investigators are located at different institutions, and/or desire to
have the same administrative status as principal investigator, the
interactive research project grant (IRPG) may be used. IRPGs are groups of
individual R01s that share a common theme AND demonstrate a high level of
interaction. The IRPG program is designed to foster interdisciplinary
collaborative research activities where the exchange of data, materials, and
ideas is more important than extensive, shared resources and central
oversight. The IRPG is described at
http://grants.nih.gov/grants/guide/pa-files/PA-96-001.html can be used
for this RFA, except that the R29 mechanism will not be allowed, and only new
projects (no competing continuation applications) may be included. The NIDDK
can choose to fund individual R01 applications outside the collaborative
arrangement owing to their special scientific merit and programmatic needs and
balance. IRPGs that are not successful in the RFA can be revised and
resubmitted at the normal R01 deadlines for revised applications. The revised
applications will be reviewed by standing NIH study sections, rather than by an
NIDDK convened special study section. In addition, it is not guaranteed that
individual RO1 projects of a revised IRPG will be reviewed by the same study
section.
Applicants are encouraged to develop the organizational structure that works
best to promote the overall research goals of the project. The
organizational structure and a plan for oversight of the entire project
should be detailed in the application.
FUNDS AVAILABLE
The NIDDK intends to commit approximately $6 million (total costs) in FY 2002
to fund 2 to 8 new awards in response to this RFA. An applicant may request
a project period of up to 5 years. It is anticipated that the size of the
awards will vary because the nature and scope of research programs proposed
will vary. The requested budget for a large R01 grant with or without
multiple subcontracts or the combined budgets for an IRPG may be up to $2
million direct costs per year (excluding F&A costs for subcontracts).
Successful applicants will have the opportunity to request additional funds
for the development of infrastructure and bioinformatics resources, and for
the purchase of large equipment. Well justified requests designed to
accelerate the progress/productivity of the project will be considered on a
case-by-case basis, contingent on the availability of funds. Principal
Investigators anticipating the submission of applications with direct cost
budgets of $500,000 or more per year MUST consult with the program official
listed under INQUIRIES prior to extensive preparation of the application, in
order to obtain prior approval to submit such an application. Although the
financial plans of the NIDDK 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 applications of outstanding scientific and
technical merit. At this time, it is not known if this RFA will be reissued.
RESEARCH OBJECTIVES
Background
Beta cells of the adult pancreas are found in the islets of Langerhans in
close contact with other endocrine cells, specifically, the alpha and delta
cells that secrete the counter-regulatory hormones, glucagon and
somatostatin, and a small population of poorly understood endocrine cells
that secrete pancreatic polypeptide. Inter- and intracellular signaling by
the cells of the pancreatic islet in response to glucose and other
metabolites and hormones, as well as the interaction of these cells with
their microenvironment, are all thought to be critical to the proper
functioning of the beta cell. The beta cell plays a central role in the
regulation of energy metabolism. The controlled release of insulin in
response to a meal or to other cellular signals is essential for the uptake
of glucose from the blood, storage of glycogen and lipid, and regulation of
DNA and protein synthesis. Failure of the beta cell to properly synthesize
and secrete insulin in response to changes in nutrient status results in
diabetes mellitus. Since ideal glucose homeostasis is rarely attained by
insulin therapy, patients with diabetes remain at risk for the development of
serious long-term complications, such as kidney failure, loss of limbs,
blindness, and heart disease.
This RFA is a direct response to recommendations of the Congressionally-
established Diabetes Research Working Group detailed in its report
“Conquering Diabetes, A Strategic Plan for the 21st Century”,
http://www.niddk.nih.gov/federal/dwg/dwgsummary.htm. One of the
extraordinary research opportunities recommended by the plan was to better
define signaling in the beta cell. Subsequently, the NIDDK initiated the
“Comprehensive Beta Cell Project” to develop a greater knowledge of beta cell
development, structure, and function with the goal of developing new
approaches to the treatment of diabetes. This current initiative is one of
several ongoing initiatives. The “Functional Genomics of the Developing
Endocrine Pancreas” project
http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-99-007.html
is using genomics approaches to enumerate all the unique
protein coding regions in the developing and adult, human and mouse beta
cells, and to clone the associated mRNAs. The ongoing results of this effort
can be found in the “Endocrine Pancreas Consortium Database”,
http://www.cbil.upenn.edu/EPConDB. Information in this database may help to
identify new areas of research opportunity and promote additional studies in
the beta cell and pancreatic islet. Another component of the “Comprehensive
Beta Cell Project,” the “Beta Cell Consortium,” is designed to bring together
multidisciplinary teams of researchers to gain a better understanding of beta
cell development and differentiation in hopes of obtaining an unlimited
supply of new beta cells or islets for use in long-term treatment of type 1
diabetes mellitus
(http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-01-014.html).
Studies directed at improving methods for islet cell
transplantation
(http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-99-006.html),
at developing gene transfer approaches to enhance islet
transplantation
(http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-01-006.html),
and for developing new technologies for beta cell imaging
(http://grants.nih.gov/grants/guide/rfa-files/RFA-DK-02-002.html) have been
issued.
Much of the beta cell research reported to date has been carried out in cell
lines derived from insulin-producing tumors (e.g., mouse and rat
insulinomas), and in modified neuroendocrine cells (e.g., mouse AtT20 cells).
These cell lines have proven very useful for in vitro studies of insulin
secretion. However, these culture systems do not accurately recapitulate
all of the normal physiology of the beta cell in the pancreas. Interaction
of the various endocrine cell types of the islet with each other, and with
their microenvironment, is critical to the proper functioning of the adult
beta cell.
The challenge that is upon us now is to understand more fully the complete
signaling environment of the pancreatic beta cell. To achieve this
formidable goal it will be necessary to determine which proteins are
expressed specifically in the beta cell, as well as in the other endocrine
cells of the adult pancreatic islet. It is also essential to understand the
intra- and intercellular signaling pathways that lead to responses such as
insulin secretion and amino acid transport; To elucidate the many signaling
pathways initiated at the plasma membrane, and to determine the molecules
(proteins, lipids, small metabolites and ions) important for integration of
these signals in the cytoplasm, and in the nucleus where complex cellular
machinery regulates the transcription and translation of beta cell specific
genes; To understand the interactions between the different cell-types of the
pancreatic islet and the extracellular matrix, both in time and space, and to
elucidate how these signaling pathways may be different in healthy islets and
in the dysfunctional islets resulting from the development of diabetes
mellitus. The use of gene inactivation and protein knock-in and knock-out
experiments to study the role of newly identified beta cell proteins in whole
animal physiology will be important. Further more, although it remains
instructive to use immortalized beta cell lines to characterize potential
ligands and intracellular binding partners for newly discovered beta cell
receptors, to identify potential substrates for beta cell specific enzymes,
as well as to try to understand the complex signaling networks functioning in
the beta cell, all findings will ultimately need to be confirmed in a
physiologically relevant milieu such as freshly isolated islets, islets
produced via differentiation of progenitor cells or in improved beta cell
models, as they become available.
Scope of Research
The NIDDK intends to support multidisciplinary investigator-initiated
projects that explore fundamental aspects of beta cell biology.
Investigators applying to this RFA are encouraged to use genome-wide studies
(genomics and proteomics), advanced imaging techniques, analytic methods, and
state-of-the art cell biological approaches to investigate broad areas of
research opportunity in the beta cell biology in order to:
o Obtain a comprehensive knowledge of the many cell-specific surface
molecules involved in the response of beta cells to extracellular signals,
determine their interaction partners, and investigate how these interactions
are impacted by nutrients and hormones, as well as by regulatory signals from
other endocrine cells of the islet.
o Delineate the signaling networks in the cytoplasm and the nucleus of the
beta cell responsible for amplification and integration of signals initiated
at the plasma membrane both in time and space, and elucidate how these
signaling pathways differ in healthy beta cells/islets, and in the altered or
dysfunctional beta cells/islets resulting from or contributing to the
development of diabetes mellitus.
o Understand the roles played by cell-cell contact and extracellular matrix
components in the islet, in signaling to and from the beta cell.
o Understand the metabolic networks and the control of flux of substrates,
intermediates, and products in the beta cell and the pancreatic islet in
response to nutrients, hormones, growth factors, cytokines, and
neurotransmitters.
Topics of research that may be part of these comprehensive projects may
include, but are not limited to the following:
o Explore the function of newly identified proteins specific for the beta
cell. For example, determine their subcellular localization, their
interaction partners, and role in beta cell function.
o Determine the hormone, growth factor, and/or cytokine receptors and/or
channels that are important for beta cell integrity and function.
o Elucidate the role of cytoskeletal elements and motor assemblies in the
normal functioning of the beta cell.
o Develop and use transgenic and knockout animal models to investigate the
function of various beta cell proteins in their physiological context(s).
o Explore which co-activators and co-repressors are responsible for
regulating the transcription of beta cell specific genes.
o Develop and use model cell systems to study how different extracellular
matrix components or synthetic substrata impact beta cell survival and
function. An example might be to develop a successful, functioning co-
culture of two or more pancreatic islet cell types.
o Investigate the extent to which the different cell populations in the
pancreatic islet function as a synchronous and integrated unit coordinating
their responses to nutrients through changes in electrical activity, and the
synthesis and release of insulin and other hormones.
o Investigate the normal physiology of the individual cell populations that
constitute the pancreatic islet, study the impact of the development of
diabetes on gene and protein expression levels, and predict how normal and
diseased beta cells respond to various metabolic challenges, nutritional
states, and drug interventions.
o Study proteins specific to the beta cell that are involved in glucose
sensing, transcription of insulin responsive genes, or maintenance of the
beta cell phenotype.
SPECIAL REQUIREMENTS
Recipients of this award, as well as designated key personnel or senior
investigators, are expected to attend annual Comprehensive Studies in Beta
Cell Biology meetings to be held in Bethesda, Maryland, along with institute
staff and other NIDDK supported investigators. The goal of these meetings
will be to facilitate progress by providing a forum for sharing ideas,
technology, skills, tools, data, and biological reagents among investigators
focused on various aspects of Beta Cell Biology. Therefore, applicants must
budget for travel funds that will allow the principal investigator, and other
key research scientists, to participate in these meetings.
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 are 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 complete copy of the updated Guidelines are 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.
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.
REQUIRED EDUCATION ON THE PROTECTION OF HUMAN SUBJECT PARTICIPANTS
NIH policy requires education on the protection of human subject participants
for all investigators submitting NIH proposals for research involving human
subjects. This policy announcement is found in the NIH Guide for Grants and
Contracts Announcement dated June 5, 2000, at the following website:
http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
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:
http://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.
PRE-APPLICATION WORKSHOP
A workshop will be held prior to the submission deadline for grants
responding to this RFA. The workshop, “Beta Cell Biology in the 21st Century:
Engineering a Pathway to Greater Understanding,” will be held on November 26-
28, 2001 on the NIH campus in Bethesda, Maryland at the Natcher Conference
Center. The purpose of the workshop is to highlight current state-of-the-art
research relevant to inter- and intracellular signaling networks in the adult
pancreatic beta cell and other related cellular systems. The workshop will
bring together investigators from multiple disciplines with interests in
numerous aspects of cell biology such as vesicle trafficking and secretion,
nutrient regulation of gene transcription, whole cell genomics and
proteomics, animal models of disease, and signaling networks within cells,
between cells, and in relation to the extracellular environment. Through
this workshop, the NIDDK hopes to establish a research agenda for the
pancreatic beta cell, and to help foster interdisciplinary activities to
further these objectives. Additional information about the workshop can be
found at http://www.betacellbiology.niddk.nih.gov. The workshop will
conclude with a public briefing for those interested in responding to this
RFA. While attendance is encouraged, it is not required that prospective
applicants attend the workshop.
LETTER OF INTENT
Prospective applicants are asked to submit a letter of intent that includes a
descriptive title of the proposed research, the name, address, and telephone
number of the Principal Investigator(s); the 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
a subsequent application, the information that it contains allows IC staff to
estimate the potential review workload and plan the review.
The letter of intent is to be sent to:
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Rm. 752 MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
APPLICATION PROCEDURES
The research grant application form PHS 398 (rev. 5/01) at
http://grants.nih.gov/grants/funding/phs398/phs398.html is to be used in
applying for these grants with the modifications listed below if preparing an
IRPG or large R01 with subcontracts.
Potential applicants are strongly encouraged to contact program staff for
pre-application guidelines to help ensure that applications will be
responsive to the NIDDK mission and intent for this program. Applications
requesting $500,000 or more in direct costs for any year MUST contact the
NIDDK program staff before submitting the application, i.e., as plans for the
study are being developed. Furthermore, the application must obtain
agreement from the staff that the NIDDK will accept the application for
consideration for award. Finally, the applicant must identify, in a cover
letter sent with the application, the staff member and who agreed to accept
assignment of the application.
Special Instructions to Applicants
Applicants should state their willingness to share data with the community at
large by timely submission of data to public databases or by making the
information available to the scientific community in another way. Applicants
should also state their willingness to share freely reagents such as knock-in
and knock-out mice, expression vectors, and antibodies.
INSTRUCTIONS FOR PREPARING LARGE R01S WITH SEVERAL SUBCONTRACTS
The following instructions address ONLY the parts of the PHS 398 research
grant application form for which information about the proposed interactive
research is requested. All other parts of the grant application should be
prepared according to the instructions in the PHS 398 booklet (rev. 5/01).
The application should specify the administrative and organizational
structure that will be used to support the research, and the synergies
enabled by the structure. It is anticipated that these projects will be
multi-disciplinary and will draw on a variety of resources. Thus, a well
thought-out and carefully described organization will be required. The PI is
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 (and reallocated, if necessary) to meet those
goals.
The application should explain how different components of the organization,
including key personnel, will interact, why they are essential to
accomplishing the research, and how the combined resources create
capabilities that are more than the sum of the parts. If any of the
components is physically separated from the others (i.e., different
departments or institutions), the application should address how that
separation will be managed. The NIDDK does not specify a specific
organizational structure, preferring that applicants develop the structure
they feel will best promote the research. However, applicants should note
that the effectiveness of the proposed structure will be a criterion of the
evaluation prior to an award and will be monitored after an award is made.
A timeline for the project should be presented. This timeline should
indicate how the project's goals can be met within the time frame of the
grant. The timeline will also assist the investigators, NIDDK, and its
advisors in evaluating progress toward the project's goals. In many cases
applicants may choose to present explicit, quantitative milestones that can
be evaluated.
If the application is to be a multi-component RO1 or an RO1 with two or more
large subcontracts, the narrative detailing the integrated activities of all
projects (a-d) can be up to 40 pages. Please note that there is no
requirement to submit this maximum number of pages. Concise, articulate
applications are desired.
INSTRUCTIONS FOR INTERACTIVE RESEARCH GRANT PROJECTS (IRPG)
An IRPG should consist of at least two investigator-initiated applications
for independent research on related topics, with a formalized agreement to
collaborate in specific ways to enhance the achievement of the goals of all
of the projects. The collaboration may involve limited shared resources.
The IRPG, therefore, offers a means of promoting collaborative efforts
between or among projects that are scientifically related, while providing a
record of independently obtained awards and retaining the research autonomy
of each principal investigator. Each principal investigator may apply for
competing supplements to support promising new research directions as they
evolve. Other benefits of the IRPG program include the establishment of
collaborations on an equal footing at separate sites (including foreign
locations) and the possibility of transferring an award with the principal
investigator to another institution without disrupting the IRPG group.
Furthermore, each participating investigator may benefit because the IRPG
establishes a larger framework of reference for the proposed work and fosters
formal collaborations tailored to achieving investigator-initiated research
objectives.
Instructions for preparing an IRPG application are described in
http://grants.nih.gov/grants/guide/pa-files/PA-96-001.html and can be used
for this RFA except that the R29 mechanism will not be allowed, only new
projects (no competing continuation applications) may be included in the IRPG.
For components requesting greater than $250,000 direct costs in any year must
follow the detailed budget directions found in the traditional PHS 398
application instructions.
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:
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.
Submit a signed, typewritten 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 must be
sent to:
Chief, Review Branch
Division of Extramural Activities, NIDDK
6707 Democracy Boulevard, Rm. 752 MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Applications must be received by the application receipt date listed in the
heading of the RFA. If an application is received after that date, it will
be returned to the applicant without review. Supplemental documents
containing significant revision or additions will not be accepted, unless
applicants are notified by the Scientific Review Administrator.
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 the CSR and
responsiveness by the NIDDK. Incomplete and/or non-responsive applications
will be returned to the applicant without further consideration.
Applicants are encouraged to submit and describe their own ideas about how
best to meet the goals of this RFA. All applications will be judged on the
basis of the scientific merit of the proposed project and the documented
ability of the investigators to meet the RESEARCH OBJECTIVES. Although the
technical merit of the proposed protocol is important, it will not be the
sole criterion for evaluation of a study. Other factors considered to be
important for review include demonstrated expertise in signaling,
endocrinology, cell biology, physiology, transgenic methodologies, mouse
genetics, functional imaging, or beta cell biology; a multi-disciplinary team
of collaborators; substantial interactions among collaborating researchers;
and demonstration of appropriate facilities and resources.
For IRPG applications and applications with distinct
subprojects/subcontracts, the initial review group will evaluate the
scientific merit of each individual effort. Additionally, the initial review
group will consider the overall strength and likelihood of effective
collaboration and the potential importance/contribution of the individual
projects to the success of the overall effort. Any core facilities or shared
resources will be assessed for their quality, cost-effectiveness and utility
to the overall effort. As part of the initial merit review, all applications
will 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 NIDDK Advisory Council.
Review Criteria
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health. To
ensure that applications from this Comprehensive Beta Cell Biology program
are evaluated appropriately, the standard NIH review criteria will be
considered as adapted below. This RFA strongly encourages collaborative
studies and thus the organizational structure and plans for collaboration as
a means of meeting the program goals will also be evaluated. In the written
comments reviewers 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.
(1) Significance: Does this study address an important problem in beta cell
biology? If the aims of the application are achieved, how will scientific
knowledge be advanced? What will be the effect of these studies on the
concepts or methods that drive this field?
(2) Approach: Are the conceptual framework, design, methods, and analyses
adequately developed, well integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics? What is the scientific gain from combining multiple
components (i.e., the degree of interrelatedness and synergy among the
components and the appropriateness of the organizational design)? Is the
management plan appropriate and of high quality for the type of project
proposed? Where appropriate, are adequate bioinformatics plans to store,
organize, analyze, or visualize data that is generated from the projects
presented?
(3) Innovation: Does the project employ novel concepts, approaches or
methods in signaling and cell biology? Are the aims original and innovative?
Does the project challenge existing paradigms or develop new methodologies or
technologies that will advance the field toward a cellular replacement for
diabetes?
(4) Investigator: Is the investigator appropriately trained and well suited
to carry out this work? Have collaborations been established or consultants
identified to provide appropriate depth and breadth of scientific expertise
required for the project? Where appropriate, is the PI appropriately
qualified to lead and coordinate the activities, and develop and implement
the management plan, as required for the project’s success?
(5) Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Are there adequate resources
available, including space, equipment, services, infrastructure, and
facilities? Do the proposed experiments take advantage of unique features of
the scientific environment or employ useful collaborative arrangements? Is
there evidence of institutional support?
(6) Collaboration: What is the likelihood of effective collaboration among
the investigators? Is there evidence of active collaboration? What is the
likelihood that the collaborative effort will achieve the goals of the
research project?
(7) Data Sharing: Do investigators state their willingness to submit data to
a public database in a timely fashion or make the information available to
the community at large in another way? Do the investigators agree to share
reagents such as knock-out mice, plasmids and antibodies?
In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:
o The 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 in relation to the
proposed research.
o 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 The adequacy of the proposed plan to share data, if appropriate.
SCHEDULE
Letter of Intent Receipt Date: February 13, 2002
Application Receipt Date: March 13, 2002
Peer Review Date: July, 2002
Council Review: September, 2002
Earliest Anticipated Start Date: September 30, 2002
AWARD CRITERIA
The intent of this RFA is to enable the NIDDK to assemble research projects
composed of highly qualified individuals or teams of investigators whose
complementary scientific skills and expertise will enable them to gain a
comprehensive understanding of the molecular basis of pancreatic beta cell
biology, and to generate new reagents and research tools that could result in
the prevention and treatment of diabetes.
Applications recommended by the NIDDK Advisory Council will be considered for
award based upon (a) scientific and technical merit; (b) the importance of
the proposed research in beta cell biology; (c) the degree of originality and
innovation in project design; (d) the creativity of the approaches and
technologies for the development of reagent, assays, and animal models; (e)
the likelihood for substantial contribution by the applicants to a successful
Comprehensive Studies in Beta Cell Biology Program; (f) the evidence for
willingness to work cooperatively; (g) the quality and availability of
research infrastructure and resources;(h) the availability of funds.
INQUIRIES
Inquiries concerning this RFA are encouraged. The opportunity to clarify any
issues or answer questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Dr. Carol Renfrew Haft
Program Director
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institutes of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 605
6707 Democracy Blvd. MSC-5460
Bethesda, MD 20892-5460
Telephone: (301) 594-7689
FAX: (301) 480-3503
E-mail: cr84g@nih.gov
Direct inquiries regarding review issues to:
Dr. Francisco O. Calvo
Chief, Review Branch
Division of Extramural Activities
National Institutes of Diabetes and Digestive and Kidney Diseases
6707 Democracy Boulevard, Rm. 752 MSC 5452
Bethesda, MD 20892-5452
(for express/courier service: Bethesda, MD 20817)
Telephone: (301) 594-8897
FAX: (301) 480-3505
E-mail: fc15y@nih.gov
Direct inquiries regarding fiscal matters to:
Mr. Ephraim Johnson
Grants Management Specialist
Division of Extramural Activities
National Institutes of Diabetes and Digestive and Kidney Diseases
2 Democracy Plaza, Room 726 MSC-5460
6707 Democracy Boulevard
Bethesda, MD 20892-5460
Telephone: (301) 594-8868
E-mail: ej47e@nih.gov
AUTHORITY AND REGULATIONS
This program is described in the Catalog of Federal Domestic Assistance No.
93.847. 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 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 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.
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