KV4@CU.NIH.GOV (04/19/91)
REQUEST FOR APPLICATIONS
NEW TECHNOLOGIES FOR DETECTING ALL GENES
AND CODING REGIONS IN GENOMIC DNA
RFA HG-91-02
National Center For Human Genome Research
Letter of Intent Receipt Date: June 17, 1991
Application Receipt Date: July 15, 1991
The National Center for Human Genome Research (NCHGR) invites
applications for assistance awards to support the development of
new technologies capable of (1) detecting all coding sequences
and/or genes in genomic DNA or (2) preparing complementary DNA
(cDNA) libraries that are representative of all expressed genes.
The NCHGR sponsors basic and applied research concerned with the
development and application of new technologies for the
characterization and analysis of the human genome and the genomes
of selected model organisms. The activities encompassed by the
NCHGR program include genetic and physical mapping, DNA
sequencing, informatics related to mapping and sequencing, and
technology development which will facilitate all of these
efforts. The NCHGR, in conjunction with the Department of
Energy, recently formulated a five-year plan that identifies
areas where further research, including new technology
development, is needed if the characterization of the human and
other genomes is to proceed to the degree envisioned by the
scientific community. A copy of the five-year plan is available
from: Human Genome Management Information System; Oak Ridge
National Laboratory, Oak Ridge, TN 37831-6050; telephone number
(615) 576-6669.
BACKGROUND
One of the long-range objectives of the Human Genome Program is
the sequencing of the 3 billion base pairs of human DNA and the
genomes of select model organisms. A challenge attendant upon
acquisition of a large amount of DNA sequence is the
identification of all coding sequences or genes within it. To
date only a small fraction of the estimated 50,000 to 100,000
human structural genes have been identified. While over 5,000
diseases have been identified which are genetic in origin, only a
small number of genes associated with such diseases have been
mapped and fewer have been sequenced. The GenBank nucleic acid
sequence database lists approximately 2,800 expressed protein-
coding sequences which are of human origin. Most of these data
have been accumulated through the efforts of individual
investigators whose primary interest was in a particular gene and
its biology.
There are several approaches to detecting coding information in
the genome: (1) identification of cDNAs representing expressed
genes; (2) identification of sequences conserved across species;
and (3) identification of sequences capable of being expressed,
using techniques such as exon trapping. Problems
in using these approaches for thorough screening of the genome
include the low abundance of many mRNAs and the differential
tissue or developmental expression of many genes. Given the
magnitude of the effort necessary to identify all genes and/or
coding sequences and to differentiate non-coding sequences from
coding sequences, new or significantly improved strategies need
to be developed to insure that all coding sequences located
within a region of genomic DNA can be identified and
characterized in an expeditious and cost-effective manner.
The purpose of this Request for Applications (RFA) is to solicit
applications for investigator-initiated research projects in two
areas: (1) The development of new methods of identifying coding
sequences or genes. As a guideline, contigs on the order of two
million base pairs are currently being produced in the course of
physical mapping projects and new technologies for megabase
sequencing are being developed. Thus, two megabases of DNA
appears to be a reasonable target size in which to test the
ability of any new technology to identify all coding sequences.
(2) The development of more general and efficient methods of
preparing, isolating and characterizing libraries of intact
cDNAs. Current methods are limited, labor-intensive and
inefficient. These two areas represent a major challenge in
completely analyzing complex genomes.
RESEARCH SCOPE
Projects responsive to this RFA should seek to develop new
technologies or research strategies to identify genes and/or
coding sequences in genomic DNA or to isolate cDNAs in a rapid,
thorough and cost-effective manner. Applications in the
following areas are encouraged:
- Methods of identifying all the genes or complete coding
regions directly from genomic DNA;
- New methods of generating high quality, full-length cDNAs;
- New methods of generating and ordering cDNA libraries that
are representative of the complete coding information
content of genomic DNA or of all coding regions
expressed in various tissues.
Emphasis will be on projects that are based on experimental
rather than computational approaches. Computational-based
applications which focus on new technologies and approaches to
identifying all genes or coding sequences among several million
contiguous nucleotides of genomic sequence data should be
submitted under the regular program announcement, "Mapping, DNA
Sequencing, and Technology Development in Support of the Human
Genome Program," which was published July 27, 1990 in the NIH
Guide to Grants and Contracts, Vol. 19, No. 28. Proposals that
use standard or currently available techniques for the isolation
of candidate cDNAs associated with a specific function or
phenotype will not be considered responsive.
MECHANISM OF SUPPORT
Support for this program will be through research grants (R01s).
The total amount of support available for grants under this RFA
is approximately $1.5 million for the first year of the project
and is contingent upon the appropriation of funds for this
purpose. There is no set limit on the size of each award.
Rather, each investigator should propose a budget adequate to
accomplish the work proposed. Approximately 6 awards will be
made and will be contingent upon the quality of the applications
received.
LETTER OF INTENT
Because of the specialized interest of this NCHGR program, and
the potential for overlap with other NIH programs, it is strongly
recommended that potential applicants contact NCHGR staff to
discuss research objectives. Potential applicants are also asked
to submit a letter of intent by June 17, 1991. This letter
should include a descriptive title of the proposed research, name
of the principal investigator and other key investigators and
their institutions. The letter of intent is requested in order
to provide an indication of the number and scope of applications
to be reviewed. The letter of intent does not commit the sender
to submit an application, nor is it a requirement for submission
of an application. Letters of intent should be sent to:
Bettie J. Graham, Ph.D.
Chief, Research Grants Branch
National Center for Human Genome Research
National Institutes of Health
Building 38A, Room 610
9000 Rockville Pike
Bethesda, MD 20892
Telephone: (301) 496-7531
E-MAIL: B2G@NIHCU.BITNET; B2G@CU.NIH.GOV
APPLICATION AND REVIEW PROCEDURES
Applications in response to this announcement will be reviewed in
accordance with the usual NIH peer review procedures.
Simultaneous submission of identical applications to different
NIH solicitations is not allowed, nor can essentially identical
applications be reviewed by different initial review committees.
Therefore, if the application submitted in response to this RFA
is identical to or substantially the same as one already
submitted to the NIH, but has not yet been reviewed, the
applicant will be asked to withdraw either the pending
application or the new one. Similarly, an application which 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 a previously reviewed application
which has undergone substantial revision; however, such
application must address, in the Introduction, the previous
critique.
Applications will first be screened for responsiveness to this
RFA by NIH staff. Those deemed non-responsive will be returned
to applicants or referred to the Division of Research Grants for
processing by the regular procedure. If a large number of
responsive applications is received, they will undergo a
preliminary peer review by the Genome Research Review Committee,
NCHGR, to identify the most meritorious ones. Applications that
are deemed non-competitive by this process will receive only a
brief critique and will not be reviewed further. The remaining
applications will be reviewed for scientific and technical merit
by the Genome Research Review Group, NCHGR. The second level of
review will be conducted by an appropriate national advisory
council. Review criteria include the following:
- Originality and innovativeness of the approach;
- Overall scientific and technical merit of the research;
- The potential of the proposed work to attain the research
objectives outlined in this RFA;
- Training, experience, research competence, and dedication
of the investigator(s);
- Adequacy of available facilities;
- Provision for the protection of human subjects and the
humane care of animals; and
- Appropriateness of the requested budget for the work
proposed.
Applications should be submitted using the form PHS 398 (rev.
10/88). The RFA label available in the revised application kit
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. Application kits are available in the business or grants
office at most academic or research institutions, or from the
Division of Research Grants, National Institutes of Health.
Applications will be accepted in accordance with the following
schedule:
TIMETABLE:
Receipt Date: July 15, 1991
IRG Review: November 1991
Council Review: February 1992
Earliest Funding Date: April 1992
It is essential that applicants type " New Technologies for
Detecting Genes in Genomic DNA" and the RFA number, HG-91-02, on
line 2 on the face page of the application form. The original
and four copies of the application should be submitted to:
Grant Application Receipt Office
Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
5333 Westbard Avenue
Bethesda, MD 20892
To expedite the review process, it is also important to submit
two copies of the application directly to:
Office of Scientific Review
National Center for Human Genome Research
National Institutes of Health
Building 38A, Room 604
9000 Rockville Pike
Bethesda, MD 20892
It is important to send these two copies to the NCHGR at the same
time as the original and four copies are sent to the Division of
Research Grants; otherwise the NCHGR cannot guarantee that the
application will be reviewed in competition for the RFA.
Funding decisions will be based on recommendations of the initial
review group and the advisory council regarding scientific merit
and program relevance, and on the availability of funds.
Prospective applicants are encouraged to contact staff very early
in the planning phase of the application. For more information
regarding the program, please contact:
Bettie J. Graham, Ph.D.
Chief, Research Grants Branch
National Center for Human Genome Research
Building 38A, Room 610
National Institutes of Health
Bethesda, MD 20892
Telephone: (301) 496-7531
E-mail: B2G@NIHCU.BITNET; B2G@CU.NIH.GOV
For information about PHS Grant Policy, applicants may contact:
Ms. Alice Thomas
Chief, Grants and Contracts Management Branch
National Center for Human Genome Research
Building 38A, Room 613
National Institutes of Health
Bethesda, Maryland 20892
Telephone: (301) 402-0733
The program and grants management officials welcome the
opportunity to clarify any issues or questions related to this
RFA and encourage written or telephone inquiries.
This program is described in the Catalog of Federal Domestic
Assistance No. 93.172. Awards will be made under the authority
of the Public Health Service Act, Sections 301 (Public Law
78-410, as amended 42 U.S.C. 241) and 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 requirement of Executive Order 12372 or to Health Systems
Agency review.