ORTHOPOXVIRUS GENOMICS AND BIOINFORMATICS RESOURCE CENTER
Release Date: October 20, 1999
RFA: AI-00-003
National Institute of Allergy and Infectious Diseases
Letter of Intent Receipt Date: December 15, 1999
Application Receipt Date: January 19, 2000
PURPOSE
As part of DHHS-wide efforts directed towards improving the
defense of civilians from the threat of possible
bioterrorism, the Division of Microbiology and Infectious
Diseases (DMID), National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health
(NIH), invites research proposals directed toward the design
and implementation of an ORTHOPOXVIRUS GENOMICS AND
BIOINFORMATICS RESOURCE CENTER. Genomic analyses will
include sequence and functional comparisons of conserved and
variable genes to provide insights for the selection of
targets for the design of antiviral and vaccine strategies.
Areas of research which should be addressed by applicants
include (but are not limited to): 1) The collection and/or
determination of orthopoxvirus genomic sequences including
variola and human and vertebrate (including human)
poxviruses that might serve as surrogates for variola; 2)
The design and maintenance of relational databases to store,
display, annotate and query genome sequence, structural
information, phenotypic data (e.g. drug susceptibility,
virulence, host specificity) and bibliographic information;
3) The application of innovative methods for global
functional analysis of the viral genomes; and 4)Service as a
repository of well-documented viral strains (including
clinical isolates and mutants, if relevant) and genomic
clones that are used in the genomic sequence analysis; and
5) Develop and maintain a website. NIAID will establish an
external steering committee to provide advice to the
Principal Investigator and the NIAID Scientific Coordinator
on research directions. Of the areas described above, items
1 and 2 are the main priorities for NIAID. However,
applications which propose only to sequence orthopoxviruses
are NOT responsive to this RFA.
HEALTHY PEOPLE 2000
The Public Health Service (PHS) is committed to achieving
the health promotion and disease prevention objectives of
"Healthy People 2000," a PHS-led national activity for
setting priority areas. This Request for Applications
(RFA), ORTHOPOXVIRUS GENOMICS AND BIOINFORMATICS, is related
to the priority area(s) of immunization and infectious
diseases. Potential applicants may obtain a copy of "Healthy
People 2000" at http://odphp.osophs.dhhs.gov/pubs/hp2000.
ELIGIBILITY REQUIREMENTS
Applications may be submitted by domestic for-profit and
non-profit organizations; public and private institutions,
such as universities, colleges, hospitals, laboratories,
units of State and local governments; and eligible agencies
of the Federal government. Foreign institutions are not
eligible to apply. Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply
as Principal Investigators.
MECHANISM OF SUPPORT
The administrative and funding mechanism to be used to
undertake this program will be the Cooperative Agreement
(U01), an "assistance" mechanism, rather than an
"acquisition" mechanism, in which substantial NIH scientific
and/or programmatic involvement with the awardee is
anticipated during the performance of the activity. Under
the cooperative agreement, 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 a
study funded under cooperative agreement(s) are discussed
later in this document under the section Terms and
Conditions of Award.
The total project period for applications submitted in
response to this RFA may not exceed five years. At present,
the NIAID is administratively limiting the duration of U01
cooperative agreements to four years; this administrative
limitation may change in the future. At this time, the
NIAID has not determined whether and how this solicitation
will be continued beyond the present RFA.
FUNDS AVAILABLE
The estimated total funds (direct and facilities and
administrative(F&A)costs) available for the first year of
support for all awards made under this RFA will be $500,000.
Depending on Fiscal Year 2000 budget appropriations, this
amount may increase. In Fiscal Year 2000 the NIAID plans to
fund approximately one award. The usual NIH policies
governing grants administration and management will apply.
Although this program is provided for in the financial plans
of the NIAID, awards pursuant to this RFA are contingent
upon the availability of funds for this purpose and the
receipt of a sufficient number of applications of high
scientific merit. Funding beyond the first and subsequent
years of the grant will be contingent upon satisfactory
progress during the preceding years and availability of
funds.
RESEARCH OBJECTIVES
Background
In recent years, there has been a significant change in both
the nature and degree of the threat posed by the use of
weapons of biological warfare. The risk of using such
weapons once appeared to be restricted to international
conflicts involving small numbers of industrialized nations.
However, an increasing number of developing countries, as
well as terrorist groups, and rogue individuals now view the
use of biological weapons as agents of terror, rather than
as instruments of warfare. Recent events, such as
disclosures of international biological weapons programs,
the bacterial contamination of restaurant food by cultists,
and the delivery of a putative anthrax bacterial culture to
a DC office, have dramatized both the possibility of
bioterrorist attack and the vulnerability of the U.S.
population to such an event. Although the DOD has developed
defenses for biological warfare, there are additional
concerns that need to be addressed to provide an adequate
civilian defense from this threat. One is that the
populations to be protected are different as civilians
include people of all ages and physical conditions. Thus,
the important research goals for defense against biological
agents delivered by a potential terrorist include: 1) rapid,
accurate diagnosis; 2) effective therapy for those infected;
3) protective vaccination for those at risk of exposure; and
4) basic research, which provides the essential underpinning
of the other areas.
Of the potential organisms that might be used in
bioterrorism, smallpox would likely have the most horrific
impact on the health of the U.S. Smallpox is highly
contagious and mortality is in the range of 30%. There is
no available antiviral therapy. Furthermore, the U.S.
population is essentially entirely susceptible because
routine immunization was terminated in the early 1960 s.
Even older vaccinees are vulnerable as vaccine protection
wanes significantly after ten years. As a result of the
eradication of the disease, and with the exception of the
development of fowlpox vaccine vectors, the amount of
research on smallpox and related poxviruses has decreased
significantly.
This Request for Applications (RFA) will support the
acquisition and analysis of orthopoxvirus genomic
information to facilitate its application to the development
of therapies and improved vaccines for smallpox and related
viruses.
Research Objectives and Scope
Relevant research includes, but is not limited to, the
following:
1) The collection and/or determination of orthopoxvirus
genomic sequences including variola and human and vertebrate
(including human) poxviruses that might serve as surrogates
for variola; 2) The design and maintenance of relational
databases to store, display, annotate and query genome
sequence, structural information, phenotypic data (e.g. drug
susceptibility, virulence, host specificity) and
bibliographic information; 3) The application of innovative
methods for global functional analysis of the viral genomes;
and 4) Service as a repository of well-documented viral
strains (including clinical isolates and mutants, if
relevant)and genomic clones that are used in the genomic
sequence analysis; and 5) Develop and maintain a website.
NIAID will establish an external advisory committee to
provide advice to the Principal Investigator and the NIAID
Scientific Coordinator on research directions. Of the areas
described above, items 1 and 2 are the main programmatic
priorities for NIAID. However, applications that propose
only to sequence orthopoxviruses, are NOT responsive to this
RFA.
SPECIAL REQUIREMENTS
NIAID will establish an external steering committee to
provide advice to the Principal Investigator and the NIAID
Scientific Coordinator on research directions. Funds to
support the travel of five committee members, as well as the
Principal Investigator, to attend an annual one day meeting
in Bethesda should be included in the budget. Other
meetings will be scheduled as conference calls.
TERMS AND CONDITIONS OF AWARD
The administrative and funding instrument used for this
program is the cooperative agreement (U01), an assistance
mechanism (rather than an acquisition mechanism), in which
substantial NIH scientific and/or programmatic involvement
with the awardee is anticipated during the performance of
the activity. Under the cooperative agreement, 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.
Consistent with this concept, 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 research will be shared among
the awardees and the NIAID Scientific Coordinator.
Cooperative agreements are subject to the administrative
requirements outlined in OMB circulars A-102 and A-110. All
pertinent HHS, PHS, and NIH grant regulations, policies and
procedures, with particular emphasis on PHS regulations at
42 CFR part 52 and HHS regulations at CFR 45 Part74, are
applicable. These special terms and conditions pertaining to
the scope and nature of the interaction between the NIAID
and the investigators will be incorporated in the Notice of
Grant Award. However, these terms will be in addition to,
not in lieu of, the customary programmatic and financial
negotiations that occur in the administration of cooperative
agreements.
1. AWARDEE RIGHTS AND RESPONSIBILITIES
Awardees will have primary responsibility for defining the
research objectives, approaches and details of the projects
within the guidelines of the RFA and for performing the
scientific activity. Specifically, awardees have primary
responsibility as described below.
a. The Principal Investigator defines the details of the
project within the guidelines of the RFA, retains primary
responsibility for the performance of the scientific
activity, and agrees to accept close assistance of NIAID
staff in aspects of scientific and technical management of
the project in accordance with the terms mutually agreed
upon prior to the award.
b. The awardee is to plan and conduct the research
stipulated in the application and to ensure that the results
obtained are analyzed and published in a timely manner. The
awardee should adhere to NIAID policy on release of genome
sequence data (March 19, 1999 issue of the NIH Guide).
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.
c. The awardee is to participate in an annual meeting of
investigators funded under this and related RFAs to discuss
progress and strategies for future research.
d. The awardee, as described above, is to participate in
meetings of the steering committee.
2. NIAID STAFF RESPONSIBILITIES
Assistance via Cooperative Agreement differs from the
traditional research grant in that, in addition to the
normal programmatic and administrative stewardship
responsibilities, the component awarding the Cooperative
Agreement anticipates substantial programmatic involvement
during performance of the project. NIAID staff will
participate in, but not direct, the research to ensure that
important disease targets are addressed. The Chief,
Virology Branch, DMID will serve as Scientific Coordinator
and will participate as a member of the research team. The
Scientific Coordinator will interact with the Principal
Investigators and Co-investigators in the overall research
planning and in data analysis. During performance of the
award, the NIAID Scientific Coordinator may provide
appropriate assistance by participating in the design of
research group activities; advising in the selection of
sources or resources; coordinating or participating in
collection and/or analysis of data; and, advising in
management and technical performance. The Scientific
Coordinator may assist with arrangements for the further
evaluation, both in vitro and in animal models, of agents
resulting from this research. However, the role of NIAID
will be to facilitate and not to direct the activities.
Specifically, it is presently envisioned that the NIAID will
be actively engaged in the facilitation of components
including assisting the awardees in:
a. Collaborative participation in overall research planning
and data analysis. Specifically, the NIAID Scientific
Coordinator may suggest studies within the scope of the
award's objectives and research activities; may present to
the investigators experimental findings from published
sources or from contract projects in support of these
suggestions; may participate in the design of experiments;
and may participate in the analysis of results.
b. Provision of needed resources and information that may
not be otherwise available to the investigator. This will
include the facilitation of collaborations between awardee
and awardees funded under other components of the
Bioterrorism program to expedite application of genetic
information to the development of drugs, diagnostics and
vaccines.
c. In the event that an awardee's research results in a
procedure or a product that requires testing of a nature
beyond the awardee's capabilities, the NIAID Scientific
Coordinator may provide resources available to the Institute
for comprehensive preclinical efficacy evaluations.
d. Coordination of consultations with the Steering Committee
and implementation of their recommendations which the
Principal Investigator and NIAID Scientific Coordinator
agree warrant action.
e. Coordination of communications and collaborations, when
appropriate, with other genomics and or bioterrorist
research activities supported by NIAID, DoD (DARPA,
USAMRIID), CDC and DoE.
f. The NIAID Scientific Coordinator will organize an annual
symposium in Bethesda, Maryland at which the Principal
Investigators will discuss their progress. This will
facilitate overall program planning and development, the
evaluation of the feasibility of the attempted approaches,
and will promote productive interactions among the
successful applicants. The NIAID Scientific Coordinator
will also ensure the participation in this symposium of
investigators from other NIAID preclinical and clinical
programs to provide the most relevant antiviral expertise
possible to facilitate planning for future research and
expedite the design and development of novel antiviral
agents.
3. Collaborative Responsibilities
NIAID will establish an external steering committee to
provide advice to the Principal Investigator and the NIAID
Scientific Coordinator on research directions. In planning
research programs, the awardee will consider recommendations
from the steering committee. In addition, the steering
committee will make recommendations to NIAID and the awardee
concerning policy for release and distribution of repository
reagents.
4. Arbitration
Any disagreement that may arise on scientific or
programmatic matters (within the scope of the award) between
award recipients and the NIAID may be brought to
arbitration. An arbitration panel will be composed of three
members -- one selected by the individual awardee in the
event of an individual disagreement, a second member
selected by the NIAID, and the third member with expertise
in the relevant area and selected by the two prior members
will be formed to review any scientific or programmatic
issue that is significantly restricting progress. While the
decisions of the Arbitration Panel are binding, these
special arbitration procedures will in no way affect the
awardee's right to appeal an adverse action in accordance
with PHS regulations at 42 CFR Part 50, subpart D, and HHS
regulations at 45 CFR Part 16.
LETTER OF INTENT
Prospective applicants are asked to submit, by December 15,
1999, a letter of intent that includes a descriptive title
of the overall proposed research; the name, address and
telephone number of the Principal Investigator; and the
number and title of this RFA. In addition, the letter of
intent should identify other key personnel who will be
involved in the research and their institutions. Although
the 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 subsequent applications, the
information that it contains allows NIAID staff to estimate
the potential review workload and to avoid conflict of
interest in the review. The letter of intent is to be sent
to Dr. Anna Ramsey-Ewing at the address listed under
INQUIRIES.
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,
compelling rationale, and justification are 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",
published in the Federal Register of March 28, 1994 (FR 59
14508-14513) and the NIH Guide for Grants and Contracts,
Vol. 23, No. 11, March 18, 1994 which is available via the
WWW. at:
http://grants.nih.gov/grants/guide/notice-files/not94-100.html
NIH POLICY AND GUIDELINES ON THE 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 which is available
at the following URL address:
http://grants.nih.gov/grants/guide/notice-files/not98-024.html
Investigators may obtain copies from these sources or from
Dr. Catherine Laughlin (listed in INQUIRIES below) who may
also provide additional relevant information concerning the
policy.
APPLICATION PROCEDURES
Applicants are strongly encouraged to call NIAID program
staff with any questions regarding the responsiveness of
their proposed project to the goals of this RFA.
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, 6700 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-99-015) and the words ORTHOPOXVIRUS
GENOMICS AND BIOINFORMATICS 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 January 19, 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. Anna Ramsey-Ewing 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
Review Considerations
Upon receipt, applications will be reviewed for completeness
and adherence to the Special Instructions above by the NIH
Center for Scientific Review and for responsiveness by NIAID
staff; those judged to be incomplete 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 the NIAID. As
part of the initial merit review, a process will be used by
the initial review group in which all applications receive a
written critique and undergo a process in which 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 Allergy and
Infectious Diseases Advisory Council.
Review Criteria
The 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 the goal of the
RFA? 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.
AWARD CRITERIA
Funding decisions will be made on the basis of scientific
and technical merit as determined by peer review, program
balance, and the availability of funds. The earliest
anticipated date of award is September 2000.
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 (research scope and
eligibility) issues to:
Dr. Catherine Laughlin
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases
Rockledge-B Building, Room 3136
6700-B Rockledge Drive MSC 7630
Bethesda, MD 20892-7630
(zip for express mail is 20817)
Telephone: (301) 496-7453
FAX: (301) 496-8030
E-mail: CL28R@NIH.GOV
Direct inquiries regarding review issues; address the letter
of intent to; and mail two copies of the application and all
five sets of appendices to:
Anna Ramsey-Ewing, Ph.D.
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive MSC 7616, Room 2220
Bethesda, MD 20892-7616
(zip for express mail is 20817)
Telephone: (301) 435-8536
FAX: (301) 402-2638
E-mail: AR15O@NIH.GOV
Direct inquiries regarding fiscal matters to:
Annette Hanopole
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
6700-B Rockledge Drive MSC 7614, Room 2122
Bethesda, MD 20892-7614
(zip for express mail is 20817)
Telephone: (301) 496-7075
Fax: (301) 480-3780
E-mail: ahanopole@niaid.nih.gov
Schedule
Letter of intent receipt date: December 15,1999
Application receipt date: January 19, 2000
Scientific review date: June, 2000
Advisory Council date: September, 2000
Earliest award date: September, 2000
AUTHORITY AND REGULATIONS
This program is supported under authorization of the Public
Health Service Act, Sec. 301 (c), Public Law 78-410, as
amended. The Catalogue of Federal Domestic Assistance
Citations are Sec. 93.856, Microbiology and Infectious
Diseases Research, and No. 93.855 - Immunology, Allergy, and
Transplantation Research. Awards will be administered under
PHS grants policies and Federal Regulations 42 CFR Part 52
and 45 CFR Part 74. 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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