RAT GENOME DATABASE

Release Date:  March 5, 1999

RFA:  HL-99-013

P.T.

National Heart, Lung and Blood Institute
National Institute of Neurological Disorders and Stroke
National Cancer Institute
National Center for Research Resources
National Human Genome Research Institute
National Institute on Alcohol Abuse and Alcoholism
National Institute of Child Health and Human Development
National Institute of Dental and Craniofacial Research
National Institute of Diabetes and Digestive and Kidney Diseases
National Institute on Drug Abuse
National Institute of Environmental Health Sciences
National Institute of Mental Health

Letter of Intent Receipt Date: April 1, 1999
Application Receipt Date: April 26, 1999

PURPOSE

In response to the recommendations of the Rat Genome Advisory Committee and
the Report of the NIH Model Organism Database Workshop
(http://www.nhlbi.nih.gov/) the NIH proposes to establish a Rat Genome
Database (RGDB).  The objective of this RFA is to establish a database that
will collect, consolidate, and integrate data generated from ongoing rat
genetic, genomic, and related research efforts, and to make these data widely
available to the scientific community.

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),
þRat Genome Databaseþ, is related to one or more of the priority areas. 
Potential applicants may obtain a copy of "Healthy People 2000" at
http://www.crisny.org/health/us/health7.html.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
organizations, public and private, such as universities, colleges, companies,
hospitals, laboratories, units of State and Local governments, and eligible
agencies of the Federal Government.  Racial/ethnic minority individuals,
women, and persons with disabilities are encouraged to apply as Principal
Investigators.

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) R01 mechanism.  The
total project period for an application submitted in response to this RFA may
not exceed 4 years.  The anticipated award date is September 30, 1999. 
Although this RFA is a one-time solicitation, it is anticipated that there
will be an ongoing need for a database effort to organize and relate rat data,
and that funding for such a database effort will continue beyond the four
years to be funded through this RFA.

This RFA is an initiative of the Institutes listed above.  However, the awards
will be made by the National Heart, Lung, and Blood Institute (NHLBI) and will
be managed by the NHLBI and the other participating Institutes.  This grant
may not be included in the Federal Demonstration Phase 3 or the Expanded
Authorities.

FUNDS AVAILABLE

Approximately $1.7 million (including direct and facilities and administrative
costs) is available for each year in the project period.  It is anticipated
that one award will be made.  Proposed funding levels are subject to change
due to budgetary, administrative, and/or scientific considerations.

RESEARCH OBJECTIVES

Background

The rat is used extensively as a model organism for studying normal and
disease processes in the human, primarily because of an extensive body of
knowledge of rat physiological mechanisms, a significant number of rat models
that mimic human diseases, the ease of breeding the rat, and the ability to
generate inbred congenic and consomic rat strains.  Once genes are identified
in rats, pathophysiological mechanisms can be elucidated lending clues to the
identification of human genetic counter-parts.

Recognizing the usefulness of the rat as a model system, the NIH funded the
Rat Genome Project and the Rat EST Project to develop genomic tools and
resources.  The genomic information and reagents developed through these
efforts has grown at an astounding pace.  Currently more than 6,000
"anonymous" genetic markers world-wide cover the rat genome and many hundreds
of known genes are placed within this genetic framework.  In addition to the
genetic map, multiple large insert genomic libraries, radiation hybrid (RH)
cell lines and a corresponding RH map, greater than 12 normalized cDNA
libraries, allele characterization for nearly all genetic markers in 48 inbred
strains of rats, a cytogenetic map, more than 50,000 ESTs with 2,000 of them
RH mapped, and a developing rat/human/mouse syntenic map have all been
generated.  These resources have already served to enhance the power of the
rat as a model system for identifying genes responsible for disease and
health, defining gene function, understanding how genes interact with the
environment, discovering and testing new drugs, and designing new prevention
strategies.  In addition to these genomic tools for studying the rat, emerging
genetic technologies are now being applied to the rat.  The production of
transgenic rats is routine in many academic and commercial laboratories. 
These rats are being used to study hypertension and neoplasia, among other
important public health problems.  Collectively these genomic and genetic
tools enable investigators to þwalkþ between rat and mouse and human using
comparative mapping techniques, thereby providing an approach for discovery of
gene function by linking physiology, genetics, and clinical phenotypes.

The data and materials being developed by the Rat Genome and EST Projects are
presently available through websites (http://www-genome.wi.mit.edu/ ;
http://brahma.mscs.mu.edu/BIOMATH/Research/ratgenome.html ;
http://www.informatics.jax.org/rat/).  The advances in generating and
utilizing new genomic tools for the rat has produced an increased demand for
central accessibility of rat data to enhance access to the data and improve
its correlation with the existing physiological and phenotypic information
about the rat.  Thus a centralized Rat Genome Database is needed to enable
investigators from a large number of research areas and interests with a range
of computer expertise to have access to the full range of information about
the rat through one user interface.  Furthermore, a centralized effort will
provide the curation of rat data needed to provide links between
genomic/genetic data and existing physiological and phenotypic data.

This RFA calls for applications to establish and develop a comprehensive Rat
Genome Database to meet the needs of the broad research community and to
provide a foundation to enhance the use of the rat in discovering genes and
understanding their functions.  This resource will facilitate the translation
of the wealth of previously published functional and phenotypic data from rat
studies for integration with genetic and genomic data from the rat and other
organisms, including the human and mouse. 

Objectives and Scope

The primary goal of the Rat Genome Database will be to collect, consolidate,
and integrate data generated from ongoing rat genetic and genomic research
efforts and make these data widely available to the scientific community.  A
secondary but critical goal is to provide curation of mapped positions for
quantitative trait loci, known mutations and other phenotypic data.  It is
recognized that the data encompassed by this latter goal are extensive and
applicants must provide justification for their choice of data to be curated. 
The most responsive application will address the following elements:

o  A design based on rat biology:  The philosophy and design of the RGDB
should be derived from the biology of the organism, rather than the database
technology that is available.  The underlying organization of the database
should enable investigators  interested in utilizing rat genomic/genetic data
to ask critical questions about the relation of that data to their field of
interest whether it be in rat or another organism.  However, the RGDB must
recognize the hardware, software, and network capabilities of the research
communities.

o  Curation: The RGDB should be curated by experts in the field to insure the
high quality of the information and its correlation with other information
about the rat.

o  Priorities: The RGDB must set clear priorities for data content, data
capture, organization, curation, annotation, navigation, and presentation.

o  Utilization of existing database tools: Where possible, reuse or adaptation
of existing software should be proposed to take advantage of the experience of
others in the database field and to minimize expense.

o  Connection with rat research communities: A successful RGDB must have ties
to the various rat biology communities.  In addition, the RGDB must be able to
support data inquiry from the broader scientific community.

o  An advisory board:   An Advisory Board, representing scientists from the
rat community, from other communities that use rat data, and with database
expertise, should be established to provide advice and recommendations on a
consistent and continuing basis to the RGDB, the research communities
(specific and broad), and the NIH.

o  Database connections:  The RGDB should establish and maintain effective
cross-links between various model organism genomic/genetic databases, as well
as with other types of databases.

A more extensive discussion of model organism databases in general can be
found in the NIH Model Organism Database Workshop Report.  This Report may be
obtained from the NHLBI (http://www.nhlbi.nih.gov/nhlbi/nhlbi.htm) and NHGRI
(http://www.nhgri.nih.gov/) web sites or from Dr. Susan E. Old at the address
listed under INQUIRIES.

POST-AWARD MANAGEMENT

During the course of the grant period, technologies will improve,
methodologies will evolve, and the rate of progress and focus of work
supported by the RGDB may change.  It is expected that the Principal
Investigator will make any necessary adjustment in scientific direction, in
conjunction with the Advisory Committee and the NIH, to accommodate the
changing environment.  Annual Progress Reviews will be conducted by the NIH
using outside advisors to provide guidance and oversight in order to ensure
that the RGDB remains focused on appropriate goals, makes sufficient progress
in achieving the elements listed in this RFA, and maintains flexibility to
accommodate future scientific opportunities.  Funds for these Progress
Reviews, including travel for the progress review team, meeting space, etc.,
should be included in the application.  These annual Progress Review meetings
will take place either at the local institution or at the NIH.  The site will
be negotiated annually with the awardee.

LETTER OF INTENT

Prospective applicants are asked to submit, by than April 1, 1999, a letter of
intent that includes a descriptive title, the name, address, and telephone
number of the Principal Investigator, the identities of other key personnel
and participating institutions, and 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
subsequent applications, the information that it contains allows Institute
staff to estimate the potential review workload and to avoid conflict of
interest in the review.

The letter of intent is to be sent to:

C. James Scheirer, Ph.D.
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7220, MSC 7924
Bethesda, MD  20892-7924
Telephone:  (301) 435-0266
FAX:  (301) 480-3460
Email:  js110j@nih.gov

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in
applying for these grants.  These forms are available at most institutional
offices of sponsored research and 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:
GrantsInfo@nih.gov.

The RFA label available in the PHS 398 (rev. 4/98) 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
may 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, typewritten original of the application, including the
Checklist, and three signed, photocopies, in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710
BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)

At the time of submission, two additional copies of the application must also
be sent to Dr. James Scheirer, as listed under LETTER OF INTENT.

Applications must be received by April 26, 1999.  If an application is
received after that date, it will be returned to the applicant without review. 
The Center for Scientific Review (CSR) will not accept any application in
response to this announcement that is essentially the same as one currently
pending initial review, unless the applicant withdraws the pending
application.  The CSR will not accept any application that is essentially the
same as one already 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and
responsiveness by the NHLBI.  Incomplete applications will be returned to the
applicant without further consideration.  If the application is not responsive
to the RFA, CSR 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 NHLBI in accordance with the review criteria stated below.  As part of the
initial merit review, a process will be used by the initial review group in
which applications receive a written critique and undergo a process in which
only those applications deemed to have the highest scientific merit, generally
the top half of the applications under review, will be discussed, assigned a
priority score, and receive a second level review by the NHLBI National
Advisory Council.

Review Criteria

The goal of NIH-supported databases is to provide tools for use in advancing
our understanding of biological systems, improving the control of disease, and
enhancing health.  In the written comments reviewers will be asked to discuss
the following aspects of the application in order to judge the likelihood that
the proposed database will have a substantial impact on the pursuit of these
goals.  Each of these criteria will be addressed and considered in assigning
the overall score, weighting them as appropriate for each application.  Note
that the application does not need to be strong in all categories to be judged
likely to have major scientific impact and thus deserve a high priority score. 
For example, an investigator may propose to carry out important work that by
its nature is not innovative but is essential to move a field forward.

(1) Significance: Does this database address the seven elements identified in
this RFA? If the aims of the application are achieved, will scientific
knowledge be advanced? Does this database provide value added data for the
scientific communities?

(2) Approach: Are the conceptual framework, design, methods, and products
adequately developed, well-integrated, and appropriate to the aims of the
project? Does the applicant acknowledge potential problem areas and consider
alternative tactics?

(3) Innovation/Database Design: Where appropriate, does the project make the
best use of existing software, database technology, and design? When
necessary, does the project develop new methodologies or technologies? Where
appropriate, does the project employ novel concepts, approaches or methods? 

(4) Investigator: Are the investigators appropriately trained and well suited
to carry out this work? Is the work proposed appropriate to the experience
level of the principal investigator and other researchers (if any)?  Does the
investigator or collaborators have an understanding of the needs of the rat
scientific community and its relationship to the science of other communities?

(5) Environment: Does the scientific environment in which the work will be
done contribute to the probability of success? Do the proposed goals take
advantage of unique features of the scientific environment or employ useful
collaborative arrangements? Is there evidence of institutional support?

In addition to the above criteria, in accordance with NIH policy, all
applications will also be reviewed with respect to the following:

o  The reasonableness of the proposed budget and duration in relation to the
proposed research.

o  The adequacy of the proposed protection for humans, animals, or the
environment, to the extent they may be adversely affected by the project
proposed in the application.

Schedule

Letter of Intent Receipt Date:    April 1, 1999
Application Receipt Date:         April 26, 1999
Peer Review Date:                 TBD
Council Review:                   September 16-17, 1999
Earliest Anticipated Start Date:  September 30, 1999

AWARD CRITERIA

Factors that will be used to make award decisions are as follows:

o  Quality of the proposed project as determined by peer review;
o  Promise of the proposed program to accomplish the objectives listed in this
RFA;
o  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:

Susan E. Old, Ph.D.
Division of Heart and Vascular Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 9150 (MSC 7940)
Bethesda, MD  20892-7940
Telephone:  (301) 435-0477
FAX:  (301) 480-1336
Email:  so40y@nih.gov

Thomas P. Jacobs, Ph.D.
Division of Stroke, Trauma and Neurodegenerative Disorders
National Institute of Neurological Disorders and Stroke
7750 Wisconsin Avenue, Room 8A13
Bethesda, MD  20892-9155
Telephone:  (301) 496-4226
FAX:  (301) 480-1080
Email: tj12g@nih.gov

Grace L. Shen, Ph.D.,
Cancer Genetics Branch
National Cancer Institute
6130 Executive Boulevard, Room 501, MSC 7381
Rockville, MD  20892-7531
Telephone:  (301) 496-7381
FAX:  (301) 435-5226
Email:  gs35r@nih.gov

Neal B. West, Ph.D.
Comparative Medicine Area
National Center for Research Resources
6705 Rockledge Drive, Room 6030 (MSC 7965)
Bethesda, MD  20892-7965
Telephone:  (301) 435-0744
FAX:  (301) 480-3819
Email:  nealw@ncrr.nih.gov

Lisa Brooks, Ph.D.
Genome Informatics Program
National Human Genome Research Institute
38 Library Drive, Room 614, MSC 6050
Bethesda, MD  20892-6050
Telephone:  (301) 496-7531
FAX:  (301) 480-2770
Email:  lisa_brooks@nih.gov

Robert Karp, Ph.D.
Division of Basic Research
National Institute on Alcohol Abuse and Alcoholism
6000 Executive Boulevard, Suite 402, MSC 7003
Bethesda, MD  20892-7003
Telephone:  (301) 443-2239
FAX:  (301) 594-0673
Email:  rkarp@willco.niaaa.nih.gov

Steven L. Klein, Ph.D.
Developmental Biology, Genetics and Teratology Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 4B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  (301) 496-5541
FAX:  (301) 402-4083
Email: kleins@hd01.nichd.nih.gov

Eleni Kousvelari, Ph.D.
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Natcher Building, Room 4AN 18A
Bethesda, MD  20892-6402
Telephone:  (301) 594-2427
FAX:  (301)480-8318
Email: kousvelari@de45.nidr.nih.gov

Catherine McKeon, Ph.D.
Metabolic Diseases and Gene Therapy Research
National Institute of Diabetes and Digestive and Kidney Diseases
45 Center Drive, Room 5AN.18B, MSC 6600
Bethesda, MD  20892-6600
Telephone:  (301) 594-8810
FAX:  (301) 480-3503
Email:  mckeonc@ep.niddk.nih.gov

Theresa Lee, Ph.D.
Division of Basic Research
National Institute on Drug Abuse
5600 Fishers Lane, Rm. 10A-19
Rockville, MD  20857
Telephone:  (301) 443-6300
FAX:  (301) 594-6043
Email:  tl37h@nih.gov

William A. Suk, Ph.D., M.P.H.
Division of Extramural Research and Training
National Institute of Environmental Health Sciences
P.O. Box 12233
Research Triangle Park, NC  27709
Telephone:  (919) 541-0797
FAX:  (919) 541-2843
Email:  suk@niehs.nih.gov

Hemin Chin, Ph.D.
Genetics Research Branch
National Institute of Mental Health
5600 Fishers Lane, Room 10C-26
Rockville, MD  20857
Telephone:  (301) 443-1706
FAX:  (301) 443-9890
Email:  hemin@codon.nih.gov

Direct inquiries regarding fiscal matters to:

Ms. Jane Davis
Division of Extramural Affairs
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Room 7174, MSC 7926
Bethesda, MD  20892-7926
Telephone:  (301) 435-0166
FAX:  (301) 480-3310
Email:  davisj@gwgate.nhlbi.nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No.
93.837.  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. 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. 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. This is consistent with the PHS mission to
protect and advance the physical and mental health of the American people.

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