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Date: Fri, 19 Apr 91 08:19 EST
From: Dot Baker <UNCDOT@UNC.BITNET>
Subject: RFA HG-91-02    NIH Guide, April l9, l99l
To: pjones@UNCVX1.BITNET

Hello Again,
   Please post this to the NIH Listserver as:
        RFAHG9102.910419
Thanks.   Dottie
 ---------------------------- Text of forwarded message -----------------------
 
$$XID RFA HG9102 HG-91-02 P1O1 *****************************************
NEW TECHNOLOGIES FOR DETECTING ALL GENES AND CODING REGIONS
IN GENOMIC DNA
 
RFA:  HG-91-02
 
P.T. 34; K.W. 1215018, 0755045, 1002008, 1002058
 
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 has been
identified.  While over 5,000 diseases that are genetic in origin
have been identified,
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.
 
SPECIAL INSTRUCTIONS FOR INCLUSION OF WOMEN AND MINORITIES IN
RESEARCH STUDIES
 
NIH policies concerning research on human subjects apply to this
program.  For projects involving clinical research, NIH requires
applicants to give special attention to the inclusion of women and
minorities in study populations.  Basic research or clinical studies
in which human tissues cannot be identified or linked to individuals
are excluded from this requirement.  However, every effort should
be made to include human tissues from women and racial/ethnic
minorities when it is important to apply the results of the study
broadly, and this must be addressed by applicants.
 
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:
 
     o Methods of identifying all the genes or complete
       coding regions directly from genomic DNA;
 
     o New methods of generating high quality, full-length
       cDNAs;
 
     o 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 that 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 traditional 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 six awards will be made and will be contingent
upon the quality of the applications received.
 
ELIGIBILITY
 
Domestic universities, medical colleges, hospitals, and other public
or private research institutions, including State and local
government units, are eligible.  Applications from minority
investigators and women are encouraged.
 
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:
 
o Originality and innovativeness of the approach;
 
o Overall scientific and technical merit of the
research;
 
o The potential of the proposed work to attain the
research objectives outlined in this RFA;
 
o Training, experience, research competence, and
dedication of the investigator(s);
 
o Adequacy of available facilities;
 
o Provision for the protection of human subjects and
the humane care of animals; and
 
o Appropriateness of the requested budget  for the work
proposed.
 
Applications must 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 and from the Division of Research
Grants, National Institutes of Health, Westwood Building, Room 449,
Bethesda, MD 20892, telephone (301) 496-7441.  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
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, MD  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.

