Full Text CA-97-011
 
NOVEL TECHNOLOGIES FOR EVALUATION OF MOLECULAR ALTERATIONS IN TISSUE
 
NIH GUIDE, Volume 26, Number 2, January 17, 1997
 
RFA:  CA-97-011
 
P.T. 34

Keywords: 
  Biology, Cellular 
  Biology, Molecular 
  Gene Products 
  Genetic Manipulation 

 
National Cancer Institute
National Institute on Deafness and Other Communication Disorders
 
Letter of Intent Receipt Date:  February 15, 1997 and August 15, 1997
Application Receipt Date:  May 8, 1997 and November 13, 1997
 
PURPOSE
 
The Technology Development Branch of the Cancer Diagnosis Program,
Division of Cancer Treatment, Diagnosis and Centers (DCTDC), National
Cancer Institute (NCI) and the Division of Human Communication of the
National Institute on Deafness and Other Communication Disorders
(NICDC) invites applications proposing the development of novel
technologies to facilitate generation of a comprehensive molecular
profile of human tissues.  Development of these innovative
technologies is intended to impact the discovery process in research
on the biology of human disease at the level of both gene discovery
and molecular cellular biology.  This initiative supports development
of efficient, cost effective, sensitive technologies to permit the
simultaneous, rapid evaluation of the spectrum of molecular
alterations in tissue specimens and, ultimately, in single cells.
These technologies can be designed to detect genome-wide molecular
alterations at the level of DNA, RNA or protein.  Investigators may
propose technologies to scan the entire genome of a cell or tissue
for constellations of cytogenetic changes or other DNA alterations.
They may also propose development of technologies to identify changes
in gene expression at the level of both RNA and protein. Technologies
to evaluate the function status of proteins including proteins of
cellular regulatory pathways are also appropriate.  As a secondary
goal, this initiative is intended to encourage the development of all
components of integrated analytical systems including preparation of
samples, sample analysis and appropriate informatics systems for data
collection and analysis.
 
Applications may be submitted as either research project grants
(R01s) or exploratory/developmental grants (R21s).  Investigators
with sufficient preliminary data are encouraged to apply for funding
using the R01 grant mechanism.  Use of the R21 mechanism is designed
to support applications where insufficient preliminary data has been
generated to support a full R01 application.  Approximately $1.5
million from NCI and $150,000 from NIDCD will be available for each
receipt date.  It is anticipated that six to eight applications will
be funded following each round of review.
 
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), Novel Technologies for Evaluation of
Molecular Alterations in Tissue, is related to the priority area of
cancer.  Potential applicants may obtain a copy of "Healthy People
2000" (Full Report:  Stock No. 017-001-00474-0 or Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone
202-512-1800).
 
ELIGIBILITY REQUIREMENTS
 
Applications may be submitted by domestic and foreign, for-profit,
and nonprofit organizations, public and private, such as
universities, colleges, hospitals, laboratories, units of State and
local governments, and eligible agencies of the Federal government.
Applications may be from single institutions but collaborative
studies between companies developing technologies and institutions
with clinical resources and expertise are also encouraged.
Racial/ethnic minority individuals, women and persons with
disabilities are encouraged to apply as principal investigators.
 
MECHANISM OF SUPPORT
 
Support for this program will be through the National Institutes of
Health (NIH) research project grant (R01) and
exploratory/developmental grant (R21) mechanisms.  The R21 mechanism
is designed to support applications proposing novel technologies
where insufficient preliminary data has been generated to support a
full R01 application.  The total budget for R21 applications should
not exceed $100,000 and the project period should not exceed three
years.  R21 grants are not renewable but the project can be
recompeted through other mechanisms such as R01 grants.  Proposals
not meeting the R21 criteria should propose use of the R01 grant
mechanism.  The total project period for the R01 applications should
not exceed four years.  Applicants will be responsible for the
planning, direction and execution of the proposed research project.
The anticipated award dates are September 30, 1997 (1st application
receipt date) and July 1, 1998 (2nd application receipt date).
Awards will be administered under PHS grants policy as stated in the
Public Health Service Grants Policy Statement.
 
FUNDS AVAILABLE
 
Approximately $1.5 million from NCI and $150,000 from NIDCD will be
available for each receipt date.  It is anticipated that six to eight
applications will be funded following each round of review.  The
number and size of awards may vary depending on the number of
meritorious R01 and R21 applications received.  Grant awards will be
contingent on the receipt of high quality applications and the
availability of funds.
 
RESEARCH OBJECTIVES
 
Background
 
Recent advances in our understanding of the complexity of the
molecular alterations underlying human disease processes and
continued progress toward obtaining the complete sequence the human
genome have provided an opportunity to change the way research in
human disease is carried out. The continued development of new and/or
improved technologies for the simultaneous evaluation of large
numbers of molecular alterations in tissue specimens will build on
these advancements and will develop the contextual information
necessary to fully understand molecular processes underlying human
disease.  This initiative will support the development of
technologies to evaluate all or a subset of molecular alterations in
human tissue specimens and, ultimately, in single cells.  These
technologies will facilitate the evaluation of the relative
contribution of specific molecular alterations to disease processes.
 
The NCI has established the Cancer Genome Anatomy Project (CGAP) in
order to capitalize on the exciting advancements in cancer molecular
biology and genetics and the genome initiative.  CGAP has two initial
goals:  developing an index for all genes expressed in tumor tissue
and developing novel technologies for the analysis of the molecular
phenotype of tumor tissue or cells.  This initiative addresses the
second goal of CGAP by supporting the early stages of technology
development.  These technologies are intended to facilitate
development of molecular profiles of tumor cells.  These molecular
profiles will identify new targets for research and will facilitate
the generation of new testable hypotheses.  These technologies will
impact the discovery process in cancer biology research at the level
of both gene discovery and molecular cellular biology.  Once
developed, these technologies will provide information about the
molecular mechanisms underlying tumor initiation and progression.
This information may ultimately be useful clinically by facilitating
more effective cancer detection, improved diagnosis and prognosis,
selection of more effective therapies for individual patients and
more accurate monitoring response to therapies.
 
Research Goals and Scope
 
This RFA is intended to encourage applications from investigators
proposing the development of technologies for the evaluation of
molecular alterations in tissues.  The novel technologies developed
in response to this initiative will impact gene discovery and
molecular cellular biology research, but should ultimately be
appropriate for automation and adaptation to high-throughput
applications. To be useful, the technologies should be sensitive,
specific, efficient and cost effective.  Investigators may propose
the development of technologies to analyze the molecular profile of
tissue at all levels of cellular function.  For example, at the
nucleic acid level, technologies may be proposed for identification
of genetic alterations genome wide.  These may include cytogenetic
alterations or spectra of point mutations such as all possible
mutations in a single gene or mutations in multiple genes, including
genes that are members of cellular regulation pathways.  Technologies
to evaluate deletions, amplifications and other DNA alterations also
will be considered responsive to this RFA.  Technologies to determine
patterns of gene expression, including changes in patterns of DNA
methylation, are also appropriate. Protein-based technologies are
currently at an early stage of development and are particularly
encouraged.  Applications for technologies to effectively determine
patterns of protein expression and the status of proteins functioning
in pathways of cellular regulation are responsive. Technologies to
identify patterns of protein/protein or protein/nucleic acid
interactions or post-translational modifications of proteins that
result in changes in protein function are also appropriate.
 
Investigators responding to this RFA should focus their proposal on
the development of molecular detection technologies.  Discussion of
other aspects of an integrated analytical system may be presented and
may be proposed as part of the supported research, however.  The
detection technologies developed under this initiative will require
associated technologies in order to maximize their utility. An
effective method of preparing appropriate sample materials from
tissue will be necessary, for example. Information systems for the
acquisition, analysis and management of research data will also be
required. Development of these technologies may require an
interdisciplinary team approach to research.  Collaborations among
clinical and academic investigators, basic researchers developing the
technologies, engineers and specialists in bioinformatics are
encouraged.  The applications should propose development of
appropriate technologies and studies to demonstrate their utility in
analysis of tissue specimens.  The emphasis of this initiative is the
application of the technologies to the analysis of human disease but
use of other mammalian systems may be proposed for early stage
technology development and proof of principle studies.
 
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 new policy results
from the NIH Revitalization Act of 1993 (Section 492B of Public Law
103-43) and supersedes and strengthens the previous policies
(Concerning the Inclusion of Women in Study Populations, and
Concerning the Inclusion of Minorities in Study Populations), which
have been in effect since 1990.  The new policy contains some
provisions that are substantially different from the 1990 policies.
 
All investigators proposing research involving human subjects should
read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research," which have been published in the
Federal Register of March 28, 1994 (FR 59 14508-14513) and reprinted
in the NIH Guide for Grants and Contracts, Volume 23, Number 11,
March 18, 1994.
 
Investigators also may obtain copies of the policy 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 February 15, 1997 (1st
application receipt date) or August 15, 1997 (2nd application receipt
date), 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, 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 NCI staff to estimate the potential review workload
and avoid conflict of interest in the review.
 
The letter of intent is to be sent to:
 
James W. Jacobson, Ph.D.
Division of Cancer Treatment, Diagnosis and Centers
National Cancer Institute
6130 Executive Boulevard, Room 513, MSC 7388
Bethesda, MD  20892-7388
Telephone:  (301) 496-1591
FAX:  (301) 402-1037
Email:  JJ37D@NIH.GOV
 
APPLICATION PROCEDURES
 
The research grant application form PHS 398 (rev. 5/95) is to be used
in applying for these grant.  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 301/435-0714, email: ASKNIH@odrockm1.od.nih.gov, and from
the NIH program administrator listed under INQUIRIES.
 
The RFA label available in the PHS 398 (rev. 5/95) application form
must be affixed to the bottom of the face page of the application.
Failure to use this label could result in delayed processing of the
application such that it might 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.
 
Submit a signed, type-written original of the application, including
the Checklist, and three signed photocopies in one package to:
 
DIVISION OF RESEARCH GRANTS
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, SUITE 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)
 
To expedite the review process, at the time of submission, send two
additional copies of the application to:
 
MS. TOBY FRIEDBERG
REFERRAL OFFICER
NATIONAL CANCER INSTITUTE
EXECUTIVE PLAZA NORTH, ROOM 636A
6130 EXECUTIVE BOULEVARD, MSC 7405
BETHESDA, MD 20892-7405
ROCKVILLE, MD 20852 (for express/courier service)
Telephone:  (301) 496-3428
FAX:  (301) 402=0275
 
Applications must be received by May 8, 1997 (1st application receipt
date) and November 13, 1997 (2nd application receipt date).  If an
application is not received by these dates, it will be returned to
the applicant without review.  The Division of Research Grants (DRG)
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 DRG will not
accept any application that is essentially the same as one already
reviewed.  This does not preclude the submission of a substantially
revised application, but such applications must include an
introduction addressing the previous critique.
 
REVIEW CONSIDERATIONS
 
Upon receipt, applications will be reviewed for completeness by the
DRG and for responsiveness by the NCI program staff, in consultation
with the NIDCD program staff.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, DRG staff may contact the
applicant to determine whether to return the application to the
applicant or submit it for review in competition with unsolicited
applications at the next review cycle.
 
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 NCI in accordance with the review
criteria stated below.  As part of the initial merit review, a
process may be used by the initial review group in which applications
will be determined to be competitive or non-competitive based on
their scientific merit relative to other applications received in
response to the RFA.  Applications judged to be competitive will be
discussed and will be assigned a priority score.  All applicants will
receive a summary statement consisting of the reviewers' written
comments.  Summary statements for competitive applications will also
contain a summary of the review committee's discussion.  The second
level of review will be provided by the National Cancer Advisory
Board.
 
Review criteria that will be used to assess the scientific merit of
an application are:
 
o  scientific and technical merit and novelty of the proposed
technologies;
 
o  appropriateness and adequacy of the experimental approach proposed
to carry out the research;
 
o  qualifications and research experience of the Principal
Investigator and staff, particularly, but not exclusively, in the
area of the proposed research;
 
o  availability of the resources necessary to perform the research;
 
o  appropriateness of the proposed budget and duration in relation to
the proposed research;
 
NOTE:  Although R21 applications must meet all of the above criteria,
they are not required to have extensive preliminary data in support
of the proposed research project.
 
The initial review group will also examine the provisions for the
protection of human and animal subjects, the safety of the research
environment, and conformance with the NIH Guidelines for the
Inclusion of Women and Minorities as Subjects in Clinical Research.
 
AWARD CRITERIA
 
The following criteria will be considered in making funding
decisions:  the quality of the proposed project as determined by peer
review; the responsiveness of the proposed project to the goals of
this RFA; and the availability of funds.
 
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:
 
James W. Jacobson, Ph.D.
Division of Cancer Treatment, Diagnosis and Centers
National Cancer Institute
6130 Executive Boulevard, Room 513, MSC 7388
Bethesda, MD  20892-7388
Telephone:  (301) 496-0591
FAX:  (301) 402-1037
Email:  JJ37D@NIH.GOV
 
Kenneth A. Gruber, Ph.D.
Division of Human Communication
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-C, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-3458
FAX:  (301) 402-6251
Email:  kenneth_gruber@nih.gov
 
Direct inquiries regarding fiscal matters to:
 
Ms. Dawn Hewitt
Grants Administration Branch
National Cancer Institute
6120 Executive Boulevard, Room 243, MSC 7150
Bethesda, MD  20892-7150
Telephone:  (301) 496-7800, ext.  202
FAX:  (301) 496-8601
Email:  HEWITTD@GAB.NCI.NIH.GOV
 
Ms. Sharon Hunt
Grants Management Branch
Division of Extramural Activities
National Institute on Deafness and Other Communication Disorders
6120 Executive Boulevard, Room 400-B, MSC 7180
Bethesda, MD  20892-7180
Telephone:  (301) 402-0909
FAX:  (301) 402-1758
Email:  sh79f@nih.gov
 
AUTHORITY AND REGULATIONS
 
This program is described in the Catalog of Federal Domestic
Assistance No. 93.394, Cancer Detection and Diagnostic Research.
Awards are made under authorization of the Public Health Service Act,
Title IV, Part A (Public Law 78-410, as amended by Public Law 99-158,
42 USC 241 and 285) and administered under PHS grants policies and
Federal Regulations 42 CFR 52 and 45 CFR Part 74 and Part 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.
This is consistent with the PHS mission to protect and advance the
physical and mental health of the American people.  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.
 
.

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