INNOVATIVE GRANTS ON IMMUNE TOLERANCE
Release Date: February 9, 2000
RFA: AI-00-006
National Institute of Allergy and Infectious Diseases
http://www.niaid.nih.gov
National Institute of Diabetes and Digestive and Kidney Diseases
http://www.niddk.nih.gov
Letter of Intent Receipt Date: August 1, 2000
Application Receipt Date: September 14, 2000
THIS RFA USES THE MODULAR GRANT AND JUST-IN-TIME CONCEPTS. IT
INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS
THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.
PURPOSE
The National Institute of Allergy and Infectious Diseases (NIAID) and
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), National Institutes of Health (NIH), invite applications for
exploratory/developmental research project grants to support novel work
on the molecular mechanisms and applications of antigen-specific immune
tolerance, which is the selective and long-term inactivation of immune
responses. The projects should involve a high degree of innovation,
and have a clearly articulated potential to improve understanding of
immune tolerance. Investigators new to immune tolerance are
particularly encouraged to develop projects in this area. Research
projects will be supported by the exploratory/developmental research
grant mechanism, which provides the resources to carry out preliminary
tests of feasibility for new research hypotheses.
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), Innovative Grants on Immune Tolerance , is related
to the priority areas of Immunization and Infectious Diseases and
Diabetes and Chronic Diseases. Potential applicants may obtain a copy
of "Healthy People 2010" at <http://odphp.osophs.dhhs.gov/pubs/hp2000>.
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.
MECHANISM OF SUPPORT
Specific application instructions have been modified to reflect
MODULAR GRANT and JUST-IN-TIME streamlining efforts being examined
by the NIH. Complete and detailed instructions on Modular Grant
applications can be found at
http://grants.nih.gov/grants/funding/modular/modular.htm
The mechanism of support will be the Exploratory/Developmental Research
Project Grant (R21). The total project period for an application
submitted in response to this RFA may not exceed 3 years.
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.
NIH uses R21 grants to provide short-duration support for preliminary
studies of a highly speculative nature, which are expected to yield,
within a two- or three-year time frame, sufficient information upon
which to base a well-planned and rigorous series of further
investigations.
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 earliest anticipated award date is July, 2001.
FUNDS AVAILABLE
The estimated total funds (direct and facilities and administrative
[F&A] costs) available for the first year of support will be $1.7
million from NIAID. In FY 2001, the NIAID plans to fund approximately
eight to ten awards. NIDDK will provide $1.0 million in FY 2001, to
fund approximately 4-5 applications relevant to diseases within the
mission of the NIDDK. An applicant may request a project period of up
to three years and a budget for direct costs of up to $150,000 per
year, excluding F&A costs or consortium arrangements. Although this
program is provided for in the financial plans of the NIH, 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.
RESEARCH OBJECTIVES
Background
We are growing closer to the day when allergies, autoimmune diseases,
and transplant rejection will be treated by selective inactivation of
harmful immune responses, without the global impairment of protective
immunity. The past two decades of immunological research have produced
a wealth of information on the cells and molecules involved in
immunoregulation, identifying a variety of approaches to be tested for
selective immune inactivation, or tolerance induction. Of particular
note is the success achieved in defining certain mechanisms by which
antigen-specific immune tolerance can be induced in animal model
systems. Some of these mechanisms are now being tested in human
autoimmune disease and organ transplantation. There is still a strong
need to develop new concepts and practical approaches for tolerance
induction, because it is likely that a variety of protocols will be
needed to control the broad range of immune-mediated diseases that
exist in humans.
Immune-mediated diseases afflict millions of individuals and often
involve serious recurring or long-term chronic illness. As highlighted
by recent success in inducing long-term transplant tolerance in non-
human primates, very promising opportunities and important challenges
exist to develop effective protocols for the antigen-specific
prevention, or even reversal, of detrimental immune responses in human
allergy, asthma, autoimmune disease and transplantation. The
application of new technologies such as soluble MHC-peptide reagents,
the ability to conduct single cell assays, and progress in the genetic
manipulation of normal cells, offer opportunities for more definitive
analyses of the human immune system and for the construction of
experimental animal systems that more directly model human clinical
situations.
Research Objectives and Scope
The goal of this initiative is to support truly innovative projects on
immune tolerance and to encourage investigators working in other areas
of research to bring novel perspectives and expertise to this field.
High risk, high impact projects are sought that have the potential to
significantly increase our understanding of the mechanisms that induce
long-lived, antigen-specific immune tolerance for application to human
disease. Studies relevant to the etiology and/or treatment of Type 1
Diabetes are of particular interest to the NIDDK. Studies on HIV/AIDS
are excluded from this program. Exploratory/developmental research
grants (R21) will be used to provide funds to develop preliminary
studies of a very speculative nature. Within a two- or three-year
funding period, it is expected that successful projects will yield
sufficient data to support a well-planned and rigorous future grant
application to continue the work by competing within the general pool
of unsolicited applications.
Highly innovative, short-term pilot projects to evaluate new, but as
yet speculative, concepts in immune tolerance may include, but are not
limited to, research in the following areas:
o the mechanistic basis for differences in tolerance induced by
systemic versus mucosal routes,
o the identification and characterization of promising new T or B cell
molecular targets for tolerance induction,
o the parameters of tolerance induction to non-peptide self antigens,
alloantigens, or allergens,
o the molecular events responsible for the loss of tolerance to self
antigens,
o methods to extend the duration of antigen-specific tolerance,
o novel technologies to identify and quantitate tolerant T or B cells,
o the development or application of cell and tissue engineering methods
to predictably induce tolerance rather than immunity,
o the characterization of novel, antigen-specific immunosuppressive
cell types,
o the identification of mechanisms by which currently known tolerogenic
biological or pharmaceutical agents induce and maintain immune
tolerance,
o the development of simple and reliable assays for the identification
of tolerant states in humans, and
o the development of vaccine strategies to induce antigen-specific
tolerance to disease-related autoantigens or allergens.
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 subpopulations 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
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 "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which was published in the Federal
Register of March 28, 1994 (FR 59 14508-14513) and in the NIH Guide for
Grants and Contracts, Vol. 23, No. 11, March 18, 1994, available on the
web at:
<http://grants.nih.gov/grants/guide/notice-files/not94-100.html>.
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.
LETTER OF INTENT
Prospective applicants are asked to submit, by August 1, 2000, a letter
of intent that includes a descriptive title of the proposed research,
the name, address, and telephone number of the Principal Investigator,
the identities of other key personnel and participating institutions,
and the number and title of this RFA. Although a letter of intent is
not required, is not binding, does not commit the sender to submit an
application, 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 avoid conflict of interest
in the review. The letter of intent is to be sent (e-mail, fax or post)
to Dr. Nasrin Nabavi at the address listed under INQUIRIES.
APPLICATION PROCEDURES
Applicants are strongly encouraged to call NIAID or NIDDK program staff
with any questions regarding the responsiveness of their proposed
project to the goals of this RFA.
The modular grant concept establishes specific modules in which direct
costs may be requested as well as a maximum level for requested
budgets. Only limited budgetary information is required under this
approach. The just-in-time concept allows applicants to submit certain
information only when there is a possibility for an award. It is
anticipated that these changes will reduce the administrative burden
for the applicants, reviewers and Institute staff.
The research grant application form PHS 398 (rev. 4/98) is to be used
in applying for these grants, with the modifications, including a 15-
page limit for the research plan, noted below.
BUDGET INSTRUCTIONS
Modular Grant applications will request direct costs in $25,000
modules. R21 applications may request an annual maximum direct cost of
$150,000, and may be for up to two or three years.
For modular grant applications, the total direct costs must be
requested in accordance with the program guidelines and the
modifications made to the standard PHS 398 application instructions
described below:
PHS 398
o FACE PAGE: Items 7a and 7b should be completed, indicating Direct
Costs (in $25,000 increments up to a maximum of $150,000) and Total
Costs [Modular Total Direct plus Facilities and Administrative (F&A)
costs] for the initial budget period. Items 8a and 8b should be
completed indicating the Direct and Total Costs for the entire proposed
period of support.
o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form
Page 4 of the PHS 398. It is not required and will not be accepted with
the application.
o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete
the categorical budget table on Form Page 5 of the PHS 398. It is not
required and will not be accepted with the application.
o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget
Narrative page. (See
http://grants.nih.gov/grants/funding/modular/modular.htm for sample
pages.) At the top of the page, enter the total direct costs requested
for each year. This is not a Form page.
o Under Personnel, list key project personnel, including their names,
percent of effort, and roles on the project. No individual salary
information should be provided. However, the applicant should use the
NIH appropriation language salary cap and the NIH policy for graduate
student compensation in developing the budget request.
For Consortium/Contractual costs, provide an estimate of total costs
(direct plus facilities and administrative) for each year, each rounded
to the nearest $1,000. List the individuals/organizations with whom
consortium or contractual arrangements have been made, the percent
effort of key personnel, and the role on the project. Indicate whether
the collaborating institution is foreign or domestic. The total cost
for a consortium/contractual arrangement is included in the overall
requested modular direct cost amount. Include the Letter of Intent to
establish a consortium.
Provide an additional narrative budget justification for any variation
in the number of modules requested.
o BIOGRAPHICAL SKETCH - The Biographical Sketch provides information
used by reviewers in the assessment of each individual"s
qualifications for a specific role in the proposed project, as well as
to evaluate the overall qualifications of the research team. A
biographical sketch is required for all key personnel, following the
instructions below. No more than three pages may be used for each
person. A sample biographical sketch may be viewed at:
http://grants.nih.gov/grants/funding/modular/modular.htm
- Complete the educational block at the top of the form page,
- List position(s) and any honors,
- Provide information, including overall goals and responsibilities, on
research projects ongoing or completed during the last three years.
- List selected peer-reviewed publications, with full citations.
o RESEARCH PLAN The research plan (a-d) is limited to 15 pages.
Applications that exceed the page limit will be returned without
review. An appendix may be included in the application, however, the
appendix is not to be used to circumvent the page limit of the research
plan.
o CHECKLIST - This page should be completed and submitted with the
application. If the facilities and administration (F&A) rate agreement
has been established, indicate the type of agreement and the date. All
appropriate exclusions must be applied in the calculation of the F&A
costs for the initial budget period and all future budget years.
o The applicant should provide the name and phone number of the
individual to contact concerning fiscal and administrative issues if
additional information is necessary following the initial review.
Applications are to be submitted on the grant application form PHS 398
(rev. 4/98). These forms are available at most institutional offices of
sponsored research, from the Division of Extramural Outreach and
Information Resources, National Institutes of Health, 6701 Rockledge
Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 301/710-0267,
email: grantsinfo@nih.gov, and on the internet at
http://grants.nih.gov/grants/funding/phs398/phs398.html
For purposes of identification and processing, item 2a on the face page
of the application must be marked "YES" and the RFA number "AI-00-006"
and the words "INNOVATIVE GRANTS ON IMMUNE TOLERANCE" must be entered
on the face page.
The RFA label and line 2 of the application should both indicate the
RFA number. The RFA label must be affixed to the bottom of the face
page. 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.
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.
Applications must be received by September 14, 2000. Applications not
received as a single package on the receipt date or not conforming to
the instructions contained in PHS 398 (rev. 4/98) Application Kit (as
modified in, and superseded by, the special instructions below, for the
purposes of this RFA), will be judged non-responsive and will be
returned to the applicant.
If the application submitted in response to this RFA is substantially
similar to a grant application already submitted to the NIH for review,
but that has not yet been reviewed, the applicant will be asked to
withdraw either the pending application or the new one. Simultaneous
submission of identical applications will not be allowed, nor will
essentially identical applications be reviewed by different review
committees. Therefore, an application that is essentially identical to
one that has already been reviewed cannot be submitted in response to
this RFA. This does not preclude the submission of substantial
revisions of applications already reviewed, but such applications must
include an introduction addressing the previous critique.
Submit a signed, typewritten original of the application, including the
checklist, and three signed, exact, single-sided 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 mail or courier service)
At the time of submission, two additional exact copies of the grant
application and all five sets of any appendix material must be sent to
Dr. Nasrin Nabavi at the address listed under INQUIRIES.
Applicants from institutions that have a General Clinical Research
Center (GCRC) funded by the NIH National Center for Research Resources
may wish to identify the GCRC as a resource for conducting the proposed
research. If so, a letter of agreement from either the GCRC Program
Director or Principal Investigator should be included with the
application.
REVIEW CONSIDERATIONS
Upon receipt, applications will be reviewed for completeness by the NIH
Center for Scientific Review and for responsiveness by NIAID staff,
those judged to be incomplete or not in the format specified in this
RFA will be returned to the applicant without review. Those considered
to be non-responsive will be returned without review.
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 NIAID in accordance with the review criteria
stated below. As part of the initial merit review, a process will be
used by the initial review group in which all applications will receive
a written critique but only those applications deemed to have the
highest scientific merit will be discussed, assigned a priority score,
and receive a second level review by the National Advisory Councils of
the NIAID and NIDDK.
Review Criteria
The five criteria to be used in the evaluation of grant applications
are listed below. To put those criteria in context, the following
information is contained in instructions to the peer reviewers.
The goals of NIH-supported research are to advance our understanding of
biological systems, improve the control of disease, and enhance health.
The reviewers will comment on the following aspects of the application
in their written critiques 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
by the reviewers 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 a 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? 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?
3. Innovation. Does the project employ novel concepts, approaches or
method? Are the aims original and innovative? Does the project
challenge existing paradigms or develop new methodologies or
technologies?
4. Investigator. Is the investigator appropriately trained and well
suited to carry out this work? Is the work proposed appropriate to the
experience level of the principal investigator and other researchers
(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? Is there
evidence of institutional support?
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
The personnel category will be reviewed for appropriate staffing based
on the requested percent effort. The direct costs budget request will
be reviewed for consistency with the proposed methods and specific
aims. For modular grant applications, any budgetary adjustments
recommended by the reviewers will be in $25,000 modules. The duration
of support will be reviewed to determine if it is appropriate to ensure
successful completion of the requested scope of the project.
AWARD CRITERIA
Award criteria that will be used to make award decisions include:
o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities
INQUIRIES
Inquiries concerning this RFA are encouraged. The opportunity to
clarify any issues or questions from potential applicants is welcome.
Direct inquiries regarding programmatic issues to:
Helen Quill, Ph.D.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Dr., Room 5140
Bethesda, MD 20892-7640
Telephone: (301) 496-7551
FAX: (301) 402-2571
Email: Hquill@niaid.nih.gov
Barbara Linder, M.D., Ph.D.
Division of Diabetes, Endocrinology and Metabolic Diseases
National Institute of Diabetes and Digestive and Kidney Diseases
Building 45, Room 5AN18A
Bethesda, MD 20892
Telephone: (301) 594-0021
Fax: (301) 480-3503
Email: linderb@extra.niddk.nih.gov
Direct review inquiries to:
Nasrin Nabavi, Ph.D.
Scientific Review Program,
Division of Extramural Activities, NIAID
6700-B Rockledge Dr., Room 2212, MSC 7616
Bethesda, MD 20892-7616
Telephone: (301) 435-3567
Fax: (301) 402-2638
Email: nn30t@nih.gov
Direct inquiries regarding fiscal matters to:
Ms. Pamela Fleming
Grants Management Specialist
Division of Extramural Activities, NIAID
6700-B Rockledge Dr., Room 2119, MSC 7614
Bethesda, MD 20892-7614
Telephone: (301) 402-6580
FAX: (301) 480-3708
Email: pfleming@niaid.nih.gov
Schedule:
Letter of Intent Receipt Date: August 1, 2000
Application Receipt Date: September 14, 2000
Peer Review Date: January, 2001
Council Review: June, 2001
Earliest Anticipated Start Date: July, 2001
AUTHORITY AND REGULATIONS
This program is described in the Catalogue of Federal Domestic Health
Service Act, Sections 93.856, Microbiology and Infectious Diseases
Research, No. 93.855 - Immunology, Allergy, and Transplantation
Research and 93.847 Diabetes, Endocrinology and Metabolism Research.
Awards will be made under the PHS Act Sections 301 & 405 as amended,(42
USC 241 & 284) and administered under NIH grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Part 74 & 92. This program is
not subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems review.
The Public Health Service 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.
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