Full Text RR-95-001


NIH GUIDE, Volume 23, Number 38, October 28, 1994

RFA:  RR-95-001

P.T. 34

  Animal Breed. & Facil., Scientific 
  Preservation of Organs/Tissue 

National Center for Research Resources

Letter of Intent Receipt Date:  December 1, 1994
Application Receipt Date:  January 25, 1995


The National Center for Research Resources (NCRR) invites
applications to establish a "National Resource for Transgenic
Animals," to be awarded competitively in Fiscal Year 1995.

The primary objectives of this initiative are to (1) create a
repository of embryos and embryonic stem (ES) cells of transgenic
rats and mice, and (2) conduct research to perfect cryopreservation
methods for these important animal species.  This award will
establish a resource center where embryos and ES cells are preserved,
maintained (banked), and distributed; where transgenic rats and mice
are produced on request from the maintained embryos and ES cells; and
where research is conducted to improve cryopreservation techniques.


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), National Resource for Transgenic Animals, is
related to the priority areas of immunology, reproductive biology,
atherosclerosis, carcinogenesis, and infectious diseases.  Potential
applicants may obtain a copy of "Healthy People 2000" (Full Report:
Stock No. 017-001-00474-0) or "Healthy People 2000" (Summary Report:
Stock No. 017-001-00473-1) through the Superintendent of Documents,
Government Printing Office, Washington, DC 20402-9325 (telephone


Applications may be submitted by domestic, for-profit and non-profit
organizations, public and private, such as universities, colleges,
laboratories, hospitals, or medical centers.  Applications from
foreign institutions are ineligible for the center program mechanism.
Applicant institutions must demonstrate an established research and
resource base in areas related to the RFA.  Racial/ethnic minority
individuals, women, and persons with disabilities are encouraged to
apply as Principal Investigators/Program Directors.


This RFA will use the National Institutes of Health (NIH) Animal
(Mammalian and Nonmammalian) Model, and Animal and Biological
Materials Resource grant (P40).  Responsibility for the planning,
direction, and execution of the proposed project will be solely that
of the applicant.  The total project period for an application
submitted in response to the RFA may not exceed five years.  The
anticipated award date is September 30, 1995.

Because the nature and scope of the research proposed in response to
this RFA may vary, it is anticipated that the size of an award will
vary also.  However, applicants must limit their requests to no more
than $350,000 (direct costs) for the initial budget period.  Future
budget period escalations should not exceed a four percent increase
over the previous budget period.

This RFA is a one-time solicitation.  Future unsolicited competing
continuation applications will compete with all
investigator-initiated applications and be reviewed according to the
customary peer review procedures.


The estimated funds (total costs) available for the first year of
support for this activity are approximately $500,000.  It is
anticipated that one new award for approximately $500,000 (total
costs) will be made in FY 1995.



An NCRR-sponsored conference on "Development of Transgenic Animal
Model Resources" was held in November 1990.  This conference
recommended the development of transgenic technology and
cryopreservation of transgenic embryos and sperm.  Improved
preservation of animal genetic resources through cryopreservation was
also recommended in the 1990 Report of the Committee on Preservation
of Laboratory Animal Resources, Institutes of Laboratory Animal
Resources, Commission of Life Sciences, National Research Council.
The NCRR announced RFA RR-93-002, "National Resource for Transgenic
Animals" in FY 1993.  As a result of that RFA, one award was made for
a resource grant concerning transgenic and targeted mouse mutant

Since the time of the above referenced reports, rapid progress has
been made in developing the technology necessary for production of
other transgenic animals and transgenic tissue.  Many of the studies
have involved mice, primarily because of the extremely high level of
genetic characterization of this species.  Comparatively, the genetic
characterization level of rats is considerably lower.  Despite this
factor, and considering the developed technology, unique advantages
may accrue with further development of rat transgenic models; thus, a
goal of this RFA is to extend the NCRR initiative for resources for
transgenic animals to include transgenic rats.  Basically, the four
major reasons for such a development are:

1.  The expression of a gene in one species may not give phenotypic
expression in another.  For example, the genes controlling
osteoarthritis show no phenotypic expression in the mouse, but do in
the rat.

2.  Some disease states are better defined in rats than in mice.  For
example, the steroid hormone induction of mammary cancer is well
known in the rat, but not in the mouse.  Similarly, behavioral
paradigms have been established in rats, but are difficult to study
in mice.

3.  There is often better control of reproductive events in rats.
Recovery of sperm, oocytes and embryos is comparatively easy.  Rats
require unique methods of gonadotropin administration, but are larger
than mice and more convenient for some studies.

4.  Finally, the larger body size of rats may provide unique
advantages for animal model development.


The objective of this RFA is to initiate a long-term, stable, program
for safeguarding national animal research resources of importance to
biomedical research.  This initiative will:

1.  Provide support to a center with capabilities to serve as a
multi-categorical research and service resource for the preservation
and supply of both transgenic rats and mice.  The center is to serve
biomedical research users throughout the United States.

2.  Encourage applied research on the development of improved
techniques for cryopreservation of eggs, sperm, and embryos of rats
and mice and utilization of ES cells.

3.  Incorporate the resources/equipment for the freezing and
maintenance of embryos, ES cells, sperm, and eggs of transgenic rats
and mice, and provide live animals on a full-cost recovery basis.  A
plan must be presented that describes the cost recovery procedures to
be implemented.

4.  Provide a means for extensive, long-term support to maintain the
embryos and ES cells of those rat and mouse species and models
considered to be of national importance, and which cannot be
preserved through alternate methods.

5.  Establish a national advisory committee to review, plan, and
prioritize national needs for preservation of important laboratory
animal resources.  This committee will also act as a central point
for the review and evaluation of stocks to be accepted into the
repository.  It is suggested that the committee be composed of no
fewer than five members, with the principal investigator serving as
the chairperson of the committee.  A minimum of two members from
outside the grantee institution should be appointed.  The committee
should meet formally at least twice a year during the first year, and
at least once a year thereafter.  Committee conference telephone
calls should be held on an as-needed basis to coordinate and plan the
activities of the center.

6.  Establish effective cooperation with other institutions and
organizations with similar interests to minimize costs and avoid

7.  Establish a modern database for: classification of all rat and
mouse embryos and ES cells maintained by the resource; maintenance of
nomenclature for transgenic embryos and ES cells being held; and
tracking distribution of all embryos, ES cells, or animals provided
to users of the resource.

8.  Encourage users who have developed transgenic animals with
research funds provided through the extramural programs of the
National Institutes of Health (NIH) to store constructs in the

9.  Encourage complete budgetary self-sufficiency of the center by
the end of its project period.  A detailed plan should be presented
which describes how such self-sufficiency will be achieved.

For purposes of this RFA, users of the center are defined as those
individuals who have active peer-reviewed research projects involving
transgenic animals, with highest priority given to those funded by
the extramural programs of the National Institutes of Health,
followed by those funded by other agencies of the U.S. Public Health
Service, then by those funded by other sources of peer-reviewed
research support.


Prospective applicants are asked to submit, by December 1, 1994, 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, 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 a subsequent application, the information that it contains is
helpful in planning for the review of applications.  It allows NCRR
staff to estimate the potential review workload and avoid conflict of
interest in the review.

The letter of intent is to be sent to:

Director, Laboratory Animal Sciences Program
National Center for Research Resources
Westwood Building, Room 857
Bethesda, MD  20892
Telephone:  (301) 594-7933
FAX:  (301) 594-9149


The research grant application form PHS 398 (rev. 9/91) is to be used
in applying for these grants.  These forms are available at most
institutional offices of sponsored research; from the Office of
Grants Information, Division of Research Grants, National Institutes
of Health, 5333 Westbard Avenue, Room 449, Bethesda, MD 20892,
telephone 301/710-0267; and from the program administrator listed

Budgetary Considerations - Allowable Costs

Unless otherwise indicated, allowable costs and policies governing
the research grant programs of the NIH will prevail.

It is expected that most equipment necessary to carry out this work
will already be available.  However, requests for major equipment
under this RFA will be considered.  This would include, but not be
limited to, equipment for producing and maintaining (freezing)
transgenic rat and mouse embryos, ES cells, ova, and sperm.

While costs of animal maintenance (i.e., per diem charges) for
research animals are allowable, it is expected that the costs of
production of live animals from transgenic embryos or ES cells will
be recovered from the users through a cost recovery system.
Applicants should separately identify all costs related to the
maintenance of research animals and to animal production.  Applicants
should budget for the consultant fees and travel expenses of the
national advisory committee members who will meet throughout this
period of grant support to advise on center activities.

The RFA label available in the PHS 398 (rev. 9/91) 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 2a of the face page of the application and the YES box must be

Submit a signed, typewritten original of the application, including
the Checklist, and three signed photocopies in one package to:

Division of Research Grants
National Institutes of Health
Westwood Building, Room 240
Bethesda, MD  20892**

At the time of submission, two additional copies of the application
must be sent to:

Comparative Medicine Review Committee
Office of Review
National Center for Research Resources
Westwood Building, Room 10A16
Bethesda, MD  20892

Applications must be received by close of business January 25, 1995.
If an application is received after that date, 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 substantial
revisions of applications already reviewed, but such applications
must include an introduction addressing the previous critique.


Upon receipt, applications will be reviewed for completeness by the
DRG and responsiveness by the NCRR.  Incomplete and/or non-responsive
applications will be returned to the applicant without further
consideration.  Only those applications that propose an integrated
resource including both mice and rats will be considered responsive.

Applications that are complete and responsive to the RFA will be
evaluated for scientific and technical merit in accordance with the
review criteria stated below, by an appropriate peer review group
convened by the NCRR.  As part of the initial merit review, a process
(triage) may be used by the initial review group in which
applications will be determined to be competitive or noncompetitive
based on their scientific merit relative to other applications
received in response to the RFA.  Applications judged to be
competitive will be discussed and be assigned a priority score.
Applications determined to be noncompetitive will be withdrawn from
further consideration and the principal investigator/ program
director and the official signing for the applicant organization will
be notified.

Review Criteria

The initial review of the grant applications will focus on scientific
merit and be based on the following criteria:

1.  Overall Program

o  The potential of the center to meet the objectives stated in this
RFA.  An application must describe how all objectives outlined in
this RFA will be met.

o  The scientific merit of the program as a whole, including the
significance of the overall program goals and the development of a
well-defined central focus.

o  The potential of the identified participants to develop research
programs of high scientific merit as evidenced by previous

2. Administration and Planning

o  The scientific and administrative leadership ability and
experience of the Principal Investigator and his/her commitment and
ability to devote adequate time to the effective management of the

o  The composition of the advisory committee, and how the national
needs for preservation of the laboratory animal resources will be
reviewed, planned, and prioritized.

o  Maintenance of internal communication and cooperation among the
investigators involved in the center, and adequacy of plans for such

o  Appropriateness of the budget for the various components of the

o  Appropriateness of the plan that details full-cost recovery for
production of live rats and mice from embryos or ES cells.

o  Appropriateness of the plan that describes how the resource will
achieve budgetary self-sufficiency by the end of the project period.

o  Quality of the plan to develop a database that will classify all
rat and mouse embryos and ES cells maintained by the resource;
maintain nomenclature for the transgenic embryos and ES cells being
held; and track distribution of all embryos, ES cells, or animals
sent to users of the resource.

3.  Scientific Expertise of Key Personnel

o  Quality and appropriateness of expertise available for research on
the development of improved cryopreservation techniques, maintenance
of animals, and development of the database.

o  Nature and degree of interdisciplinary approach for promoting
collaboration among scientists with expertise in transgenic animal

o  Qualifications, experience, and evidence of the commitment of the
investigators within the applicant institution, and their willingness
to interrelate with other elements proposed for the center.

4.  Institutional Commitment

o  The institutional commitment to the program, including lines of
responsibility for the proposed center and the institution's
contribution to the management capabilities of the center.

o  The degree of institutional contributions for administrative and
planning activities.

o  The research environment and the availability of expertise,
resources, equipment, and space for the freezing and maintenance of
rat and mouse embryos, ES cells, sperm, and ova of transgenic

o  The availability of expertise and resources required to provide
users with live animals from embryos or ES cells, at their request.

o  The potential for interaction with scientists from other
departments and institutions to minimize costs and avoid duplication.

o  The institutional commitment to any newly-recruited individuals
responsible for conducting essential grant functions and activities.

In compliance with NIH policy and usual practice, the initial review
group will also examine the provisions for the protection of animal
subjects and the safety of the research environment.

Following the initial scientific merit review, competitive
applications will receive a second-level review by the National
Advisory Research Resources Council.


Applications will compete for available funds with all other
applications submitted in response to this RFA and recommended by
peer review.  The following factors will be considered in making
funding decisions:

o  Quality of the application as determined by peer review o
Availability of funds
o  Overall program balance represented by the applications
recommended by peer review


Letter of Intent Receipt Date:  December 1, 1994
Application Receipt Date:       January 25, 1995
Initial Review:                 June 1995
Second Level Review:            September 1995
Anticipated Date of Award:      September 30, 1995


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:

Director, Laboratory Animal Sciences Program
Comparative Medicine Program
National Center for Research Resources
Westwood Building, Room 857
Bethesda, MD  20892
Telephone:  (301) 594-7933
FAX:  (301) 594-9149

Direct inquiries regarding fiscal matters to:

Mr. Paul Karadbil
Grants Management Office
National Center for Research Resources
Westwood Building, Room 853
Bethesda, MD  20892
Telephone:  (301) 594-7955
FAX:  (301) 594-7910


This program is described in the Catalog of Federal Domestic
Assistance No. 93.306, Laboratory Animal Sciences and Primate
Research.  Awards are made under authorization of the Public Health
Service Act, Title III, Section 301 (Public Law 78.410, as amended;
42 USC 241) and administered under PHS grants policies and Federal
Regulations 42 CFR Part 52 and 45 CFR Parts 74.  This program is not
subject to the intergovernmental review requirements of Executive
Order 12372 or Health Systems Agency review.

The Public Health Service (PHS) strongly encourages all grant
recipients to provide a smoke-free workplace and promote the non-use
of all tobacco produces.  This is consistent with the PHS mission to
protect and advance the physical and mental health of the American


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