[bionet.molbio.genome-program] NIH Human Genome Annoucement, Research Grants

JP2@CU.NIH.GOV (01/10/90)

Following is the Human Genome Program Announcement for research
grants (RO1), Program Projects (PO1), FIRST awards (R29)
Resouces related projects and biotechnology resource grants (R24, and P41),
Research Career Development Awards (K04), Conference Grants (R13),
and Small Business Innovation Research grants (SBIR, R43 and R44).
Pilot projects may be submitted under the RO1 program.



TECHNOLOGY DEVELOPMENT, MAPPING, AND DNA SEQUENCING IN SUPPORT OF THE HUMAN
GENOME PROGRAM

P.T. 34; K.W. 1215018, 0755045, 1002058, 1004017, 1003012, 1002008, 0710030

Office of Human Genome Research

This Program Announcement restates the interest of the National Institutes of
Health (NIH) in receiving research grant applications for studies related to
the Human Genome Initiative.  The present announcement supersedes the previous
NIH-wide Program Announcement (November 4, 1988) on mapping and determining
the DNA sequence of the genomes of the human or of model organisms.  The
objective is to stimulate creative, innovative research that will
substantially improve the rapidity, efficiency and accuracy with which mapping
and DNA sequence data can be obtained, analyzed, and distributed.




                   Vol. 18, No. 26, July 28, 1989 - Page 3
BACKGROUND INFORMATION

The NIH is currently engaged, along with several other federal, private, and
international organizations, in a research program known as the Human Genome
Initiative.  This program is designed to characterize the human genome and the
genomes of selected model organisms.  It has several interrelated goals:  the
construction of high resolution genetic linkage maps; the development of a
variety of physical maps; the determination of the complete nucleotide
sequence of the DNA of selected organisms; the development of the capability
for collecting, storing, distributing, and analyzing the data and materials
produced; and the development of appropriate new technologies necessary to
achieve these objectives.  The information that will be obtained within the
genome project will be a resource for studies of gene structure and function
and will promote research into the genetic aspects of human disease.  In this
way, the Human Genome Initiative will serve as an underlying source of
information for, and stimulus to, a wide range of studies from the most basic
to targeted and clinical programs across the spectrum of NIH interests and
responsibilities.

In the past two years, several announcements/solicitations for grant
applications related to the Human Genome Initiative have been published in the
NIH Guide for Grants and Contracts.  These include two broad Program
Announcements and several Requests for Applications.  This Program
Announcement consolidates the prior announcements/solicitations in one
document and emphasizes the continuing, ongoing interest on the part of the
NIH in receiving grant applications for support of research projects that
address the goals of the genome program with a wide range of research
activities.  One area in which research activities are encouraged is the
development of improved technology for physical mapping, for the determination
of DNA sequences, and for the management of the information that accrues.  A
separate, but equally important, area includes research projects that seek to
increase the information available about specific genomic regions through the
expansion of genetic maps, the construction of physical maps, or pilot
projects for large-scale DNA sequence determination.

Creative, novel approaches in all these areas will be essential to the success
of the genome project.  To this end, the NIH encourages interdisciplinary
programs that draw from fields such as information science, chemistry,
physics, and engineering, in addition to the biological sciences.

Progress will be accelerated by cooperation and interaction among
investigators.  Therefore, it is expected that all materials and information
derived from this work will be made available to the scientific community in a
timely manner, in accord with Public Health Service policy.  Within the genome
program, awardees will be expected to share information and to work closely
with other laboratories involved in related projects.

RESEARCH SCOPE

This Program Announcement is intended to emphasize the ongoing commitment of
the NIH to the specific goals of the genome project and to the development of
methodological tools and resources which would support this effort, including
the storage and retrieval of materials and data.  Applications responsive to
this announcement will include a broad spectrum of research approaches to
genetic and physical mapping, DNA sequencing, data handling and new methods of
data interpretation.  Development of new and imaginative technologies needed
to support the genome project are especially encouraged.  The topics described
below are not intended to limit the types of applications that are acceptable
in response to this announcement, but rather to illustrate the range of work
that will be needed to attain the goals of the genome project.

However, research directed toward analysis of the biological function of
specific genes or gene systems, or the application of genetic information to
the understanding, diagnosis, prevention, or treatment of specific genetic
disorders is not within the scope of the genome program.  Such work is
currently supported by a number of other programs at the NIH.  Information
about these programs can be obtained from individual Institutes.  Potential
applicants are encouraged to contact one of the representatives listed below
to discuss the proposed research project and for additional information.

Technology Development

The objective is to stimulate creative, innovative research that will lead to
substantial improvements in the speed, efficiency and accuracy with which
mapping and DNA sequence data can be obtained, analyzed, and distributed.
Such improvements can be achieved through automation of existing methodology,
development of new approaches, or both.  Multi-disciplinary approaches to the


                   Vol. 18, No. 26, July 28, 1989 - Page 4
attainment of these goals are encouraged.  Examples of the problems for which
improved technological solutions and/or automation are needed are:

  o  generating, purifying, and cloning large DNA fragments;

  o  constructing physical maps, including long-range restriction maps
     and overlapping sets (contigs) of DNA fragments that are derived
     from specific chromosomal regions and are connected into more
     extensive physical arrays;

  o  determining relationships between genetic and physical maps;

  o  locating specific genes on genetic and physical maps and within
     regions of sequenced DNA;

  o  determining DNA sequence, including assembling overlapping DNA
     sequences into longer arrays;

  o  storing, analyzing, and distributing the data obtained in each of
     these activities; and

  o  storing and distributing the materials generated by all of these
     activities.

Applicants are advised to take several general considerations into account
when designing new projects.

  o  Methodological improvements have played an important role in
     advancing biological research, never more so than in the past
     twenty years.  In general, when technology development has been
     successful, it has been driven by the desire to solve specific
     scientific problems.  Therefore, it is reasonable to expect that,
     within the context of the genome program also, the most successful
     new technologies will come from those endeavors in which the
     attempt to develop better technology occurs in the context of a
     specific research problem related to genomic analysis.  Applicants
     are encouraged to clearly define the biological problem for which
     the technological solution is being devised.  Applicants whose
     expertise is primarily non-biological and who are interested in
     addressing problems of genome analysis with new, non-biological
     tools are especially encouraged to interact closely with
     biologists.

  o  It has been suggested that to significantly increase the rate at
     which mapping and sequence data can be acquired, efforts should be
     directed toward improving by three- to five-fold the scale and/or
     efficiency with which particular steps in mapping, sequence
     determination, or data analysis can be accomplished.  Such an
     incremental increase can serve as a useful benchmark in designing a
     research program.

  o  Achievement of such a significant improvement in analytical
     capability may require entirely new approaches.  Methods that have
     been useful for addressing particular needs in the past, such as
     determining the sequence of a few kilobases of DNA, may not be
     adequate for addressing comparable problems on a much larger scale.
     The NIH recognizes that novel approaches may involve a considerable
     degree of risk and encourages submission of high-risk, high pay-off
     projects in response to this announcement.

Mapping and DNA Sequencing

The objective is to increase our knowledge of the genetic and physical maps
and the DNA sequence of selected organisms, leading up to the complete maps of
the human genome and the complete human DNA sequence.  Research projects in
the following areas are encouraged:

  o  expanding the genetic map of the human, or of those model organisms
     for which such information would serve to promote the objectives of
     the overall genome program;

  o  constructing physical maps of the chromosomes of the human and of
     model organisms, including projects for large-scale physical
     mapping; and

  o  pilot projects for large-scale DNA sequence determination,
     involving the DNA of model organisms or regions of the human
     genome.

                   Vol. 18, No. 26, July 28, 1989 - Page 5
The primary goal of research projects proposed under this section will be the
generation of a substantial amount of new mapping and/or sequence information.
The project may utilize current technology or propose new or improved
technology.  If current technology is used, it should be used at or near its
limits in order to explore its capabilities.

Because of the extensive amount of information already available about the
genetics and molecular biology of E. coli, S. cerevisiae, D. melanogaster, C.
elegans, and M. musculus, the genome program is particularly interested in
promoting study of these models.  However, research projects that involve
other models are also expected to make important contributions to the Human
Genome Initiative by means of both development of new technology and improved
understanding of genome structure through comparative studies.  Thus, no model
organism is excluded from the genome program a priori.  However, applicants
proposing to study models other than those named above must provide a
rationale, in terms of the goals of the overall genome program, for the use of
such another model.

MECHANISMS OF SUPPORT

Support for this program will be through research grants, including project
grants (R01), program project grants (P01), FIRST awards (R29), resources
related research projects and biotechnology resource grants (R24, P41),
Research Career Development Awards (K04), conference grants (R13) and Small
Business Innovation Research (SBIR) grants (R43, R44).  Because not all
institutes support all of the above mechanisms, potential applicants are
encouraged to contact the representatives listed below for additional
information.  Policies that govern research grant programs of the NIH apply to
this program.  Consortium arrangements and collaborative projects among
scientists with skills in biological sciences, chemistry, physics, information
science, and engineering are encouraged.

APPLICATION AND REVIEW PROCEDURES

Applications in response to this announcement will be reviewed in accordance
with the usual NIH peer review procedures.  They will first be reviewed for
scientific and technical merit by a special study section in the Division of
Research Grants organized for this purpose.  Following the initial review, the
applications will be considered by the appropriate National Advisory Board or
Council.  Review criteria that will be used to assess the scientific merit of
an application are the following:

  o  Scientific merit;

  o  Potential value of the research for furthering the goals of the
     genome project;

  o  Feasibility of the research and adequacy of the experimental
     design;

  o  Significance and originality of the research and methodological
     approaches, as they relate to the genome project;

  o  Training, experience, research competence, and dedication of the
     investigator(s);

  o  Adequacy of available facilities;

  o  Provisions for the protection of human subjects, the humane care of
     animals, and biosafety conditions;

  o  Appropriateness of the requested budget for the work proposed.

Because the significance of the proposed research project to the goals of the
Human Genome Initiative is a criterion for review, consultants must consider
this aspect in the evaluation of an application submitted in response to this
Program Announcement.  Applicants are, therefore, encouraged to consult with
one of the staff listed below before submission, to discuss the relevance of a
proposed application to the genome program.

METHOD OF APPLYING

Applications should be submitted on Form PHS 398 (rev.  10/88).  Application
kits are available in most institutional business offices and from the Office
of Grants Inquiries, Division of Research Grants, Westwood Building, Room 449,
National Institutes of Health, Bethesda, Maryland 20892; telephone (301)
496-7441.


                   Vol. 18, No. 26, July 28, 1989 - Page 6
Applications will be accepted in accordance with the usual NIH receipt dates
that apply for the various mechanisms listed under MECHANISMS OF SUPPORT.  It
is essential that applicants type "Technology Development, Mapping, and DNA
Sequence Determination in Support of the Human Genome Initiative" in item 2 on
the face page of the application form.  The original and six copies of the
application should be submitted to the following office:

Application Receipt Office
Division of Research Grants
Westwood Building, Room 240
National Institutes of Health
Bethesda, Maryland  20892**
Telephone:  (301) 496-7273

The conventional presentation for grant applications should be utilized.

Funding decisions will be based on recommendations of the initial review group
and of the National Advisory Council regarding scientific merit and program
relevance, as well as on the availability of funds.

INQUIRES

It is strongly recommended, but not required, that potential applicants
contact the Office of Human Genome Research (OHGR) or the staff member at the
appropriate NIH institute to discuss research objectives.

BID    CONTACT                     BUILDING     ROOM   TELEPHONE

OHGR   Bettie Graham, Ph.D.        Shannon      201    496-0844
NIDDK  Robert Katz, Ph.D.          Westwood     607    496-7997
NCI    Cheryl Marks, Ph.D.         Executive    630    496-7028
                                     Plaza South
FIC    Lynn Amende, Ph.D.          38A          613    496-6688
DRR    Charles Coulter, Ph.D.      Westwood     8A11   496-5411
NIA    Huber R. Warner, Ph.D.      31           5B39   496-6402
NICHD  Delbert Dayton, M.D.        Executive    5C19   496-5541
                                     Plaza North
NINDS  N.C. Myrianthopoulos, Ph.D. Federal      8C04   496-5821
NLM    Arthur Broering, Ph.D.      38A          8C16   496-4621
NIDR   John Townsley, Ph.D.        Westwood     506    496-7807
NIGMS  Irene Eckstrand, Ph.D.      Westwood     920    496-7137
NIAMS  Steven Hausman, Ph.D.       Westwood     403    496-7495
NHLBI  Carol Letendre, Ph.D.       Federal      506    496-6402
NIAID  William Duncan, Ph.D.       Westwood     754    496-5598
NEI    Jack McLaughin, Ph.D.       31           6A08   496-9110

Mailing address for the above offices:  Bethesda, Maryland 20892
All Bethesda telephone numbers are in area code 301.


**THE MAILING ADDRESS GIVEN FOR SENDING APPLICATIONS TO THE DIVISION OF
RESEARCH GRANTS OR CONTACTING PROGRAM STAFF IN THE WESTWOOD BUILDING IS THE
CENTRAL MAILING ADDRESS FOR THE NATIONAL INSTITUTES OF HEALTH.  APPLICANTS WHO
USE EXPRESS MAIL OR A COURIER SERVICE ARE ADVISED TO FOLLOW THE CARRIER'S
REQUIREMENTS FOR SHOWING A STREET ADDRESS.  THE ADDRESS FOR THE WESTWOOD
BUILDING IS:

5333 Westbard Avenue
Bethesda, Maryland 20816