Subject: RFA CA-9l-07 2/l5/9l NIH Guide.
From: Dot Baker <[email-masked]>
To: [email-masked]
Date: Wed, 13 Feb 91 12:53 EST

Hi Paul,
   # 2 coming to you.  Please post to the NIH Listserver as:
        RFACA-91-07.910215
                          Dottie
 ---------------------------- Text of forwarded message -----------------------
 
REQUEST FOR APPLICATIONS
 
RFA:  CA-91-07
 
MOLECULAR ANALYSES OF RADIATION-INDUCED GENETIC
DAMAGE
 
P.T. 34; K.W. 1002028, 0725015, 1002019, 1002004
 
National Cancer Institute
 
Letter of Intent Receipt Date:  April 24, 1991
Application Receipt Date:  May 24, 1991
 
I.  INTRODUCTION
 
The Division of Cancer Etiology of the National
Cancer Institute (NCI) invites grant applications from
interested investigators through an announcement of
Request for Applications (RFA) for molecular studies on
the mutagenic effects of ionizing radiation on
mammalian DNA, in vitro and in vivo.
 
II.  BACKGROUND
 
The nature and frequency of mutations induced by
exposure of mammalian cells to ionizing radiation is
not well characterized for low linear energy
transfer (LET) radiations (e.g., gamma and x-rays);
it is even less well characterized for high-LET
radiations (e.g., neutrons and alpha particles).  In
particular, it is not known if mutations induced by
ionizing radiations are preferentially distributed
at the molecular level into characteristic mutation
spectra as appears to be the case for point
mutations induced by chemical mutagens and by
ultraviolet light.  If characteristic or unique
mutation spectra could be demonstrated in mammalian
cells exposed to the various forms of ionizing
radiation, they would be candidates as molecular
markers for radiation exposure and a possible means
of distinguishing radiation-induced genetic damage
from that which occurs spontaneously or is induced
by other mutagens.
 
III.  RESEARCH GOALS AND SCOPE
 
The purpose of this RFA is to encourage research to
characterize the distributions of mutations induced
in the DNA of mammalian cells exposed to ionizing
radiations in vitro and in vivo.  The objective will
be the quantitative analyses of mutations by
location and frequency of occurrence in defined DNA
targets (or chromosomal location for large-scale
genetic events) with sufficient sensitivity and
precision to be applied directly to small
populations of somatic cells.  Primary emphasis
should be placed on basic studies with cultured
mammalian cells, including human cells.  Such
research could involve a variety of genetic
endpoints and techniques including the use of
specific gene targets, repetitive DNA sequences, and
chromosome-specific DNA probes.
 
This RFA will permit a wide range of research
activities, including, but not limited to, the
following studies:
 
o  To determine if mutation spectra based on point
mutations, deletions, and/or other mutational
endpoints may be uniquely characteristic of
radiation exposure and can be used to discriminate
between cellular exposures to the different forms of
ionizing radiation, between exposures to ionizing
radiations versus exposure to other types of
mutagens, or between mutations induced by
exposure to ionizing radiation and those of
spontaneous origin.
 
o  To determine the feasibility and merit of
amplifying mutations directly from somatic cells
without using genetic selection and subculturing to
amplify mutated DNA for molecular analysis.  In vivo
studies should consider the possible complications
that may result from the clonal expansion of
mutations in progenitor cells into populations of
somatic cells.
 
o  To investigate mutational responses in radiation-
exposed somatic cells as functions of varying doses
and dose rates.
 
o  To compare and validate radiation-induced
mutation spectra obtained with cultured cells
exposed in vitro with mutation spectra obtained from
somatic cells exposed in vivo.
 
IV.  MECHANISM OF SUPPORT
 
This program will be supported through the National
Institutes of Health (NIH) traditional research
project grant (R01).  The applicant will have the
sole responsibility for planning, directing, and
executing the proposed research.  Awards will be
administered under Public Health Service grants
policy as stated in the PHS Grants Policy Statement,
DHHS Publication No. (OASH) 90-50,000, revised
October 1, 1990.
 
The total project period for applications submitted
in response to the present RFA should not exceed
four (4) years.  The intent of this research
initiative is to fund approximately 6 individual
research grants, with total program costs not to
exceed $950,000 in total costs for the first year.  This funding
level is dependent on receipt of a sufficient number
of grant proposals of high scientific merit.
Support for this RFA is provided for in the
financial plans of the
NCI.  However, award of grants responding to this
RFA will be contingent on the availability of funds
at the time the awards are made.  Non-profit, for-
profit, and both foreign and domestic institutions
are eligible to apply.
 
Renewal applications will compete with all other
unsolicited applications and will be reviewed by a
standing Division of Research Grants (DRG) study section.
However, should the NCI determine that there is a
sufficient need for programmatic support related to
the RFA, the NCI may announce a request for renewal
applications.
 
V.  REVIEW PROCEDURES AND CRITERIA
 
a.  Review Procedures
 
Upon receipt, applications will be initially
reviewed by DRG
for completeness.  Incomplete applications will be
returned to the applicant without further
consideration.  Review of the responsiveness of
applications will be carried out by NCI program
staff.  If a grant application to the RFA is judged to
be nonresponsive, the applicant will be contacted by
program staff and given an opportunity to have the
proposal considered along with unsolicited
grant applications received.
 
Applications responsive to the RFA solicitation will be
reviewed by a review group convened by the Division
of Extramural Activities of the NCI for that
purpose.  The initial review will be for scientific
merit.  A second level of review will be carried out
by the National Cancer Advisory Board where
qualified applications will be considered
with respect to the needs and priorities of the NCI.
 
b. Review Criteria
 
Applications should be responsive to the stated
purpose and objective of the RFA.  Those factors
considered to be important for review will include:
 
1. A demonstrated knowledge of the applicable
science and competence with relevant methodology.
 
2. The scientific merit and innovation of
proposed research.
 
3. Adequacy of facilities and special resources
relevant to the RFA.
 
4. Cost effectiveness of the proposal and
quality of scientific collaboration.
 
VI.  METHOD OF APPLYING
 
Applications must be submitted on PHS 398, revised
10/88, available at most institutional business
offices and may be obtained from the Office of
Grants Inquires, DRG, NIH, Room 449, Westwood
Building, 5333 Westbard Avenue, Bethesda, Maryland
20892.  The format and instructions applicable to
individual research grant applications should be
followed in preparing a grant in response to the
RFA.
 
The RFA label available in the 10/88 revision of
Application Form 398 must be affixed to the bottom
of the face page.  Failure to use this label could
result in delayed processing of a grant application,
and could prevent it from reaching the review
committee in time for review.  In addition, the
number and title of the RFA must be typed on line
2 of the face page of the application and YES must
be checked.  A signed, typewritten original grant
application, including the checklist, and four (4)
signed, exact photocopies, must be mailed, in one
package, to the Division of Research Grants at the
address below.  The photocopies must be clear and
single-sided.
 
DIVISION OF RESEARCH GRANTS
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**
 
At the time of submission, two (2) additional copies
of the application must also be sent to:
 
REFERRAL OFFICER
Division of Extramural Activities
National Cancer Institute
Westwood Building, Room 848
5333 Westbard Avenue
Bethesda, MD  20892
 
Applications must be received by May 24, 1991.  If
an application is received after that date, it will
be returned to the applicant.
 
If the application submitted in response to this RFA is
substantially similar to a research grant application already
submitted to the NIH for review, but 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 cannot be submitted in response to this
RFA that is essentially identical to one that has already been
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.
 
Animal and human subject approval clearances, when
applicable, should be submitted with the application
to expedite the review process.
 
Letter of Intent
 
Prospective applicants are requested to submit a
letter of intent to respond to the RFA that includes
a descriptive title of the proposed research,
the
name and address of the Principal Investigator, the
names of other key personnel, the participating
institutions, and the number and title of the RFA in
response to which the application is being
submitted.  The letter of intent helps NCI staff to
estimate the review workload and to avoid possible
conflict of interest in the review.  The request for
a letter of intent does not bind the respondent to
respond formally to the RFA, nor is it a requirement to apply.
The letter of intent does not
enter into the review of applications.
 
The letter of intent must be sent to:
 
Richard A. Pelroy, Ph.D.
Radiation Effects Branch
National Cancer Institute
Executive Plaza North, Suite 530
9000 Rockville Pike
Bethesda, MD  20892
Telephone:  (301) 496-9326
 
VII. INQUIRIES
 
Written or telephone inquires concerning the
objectives and scope of this RFA are encouraged and
may be directed to Dr. Richard A. Pelroy at the
above address.
 
This program is described in the Catalog of Federal
Domestic Assistance No. 93.393, Cancer Cause and
Prevention Research.  Awards are under authorization
of Public Health Service Act, Section 301(c) and
Section 402 (Public Law 78-410, as amended; 42 USC
241; 42 USC 282) and administered under PHS grant
policies and Federal regulations 42 CFR Part 52 and
45 CFR Part 74. This program in not subject to the
intergovernmental review requirements of Executive
Order 12372 and Health Systems Agency review.