Full Text HD-93-013

TRANSGENIC MOUSE SPERM CRYOPRESERVATION

NIH Guide, Volume 22, Number 11, March 19, 1993

RFA:  HD-93-013

P.T. 34

Keywords: 
  Preservation of Organs/Tissue 
  Biological Resources 


National Institute of Child Health and Human Development

Letter of Intent Receipt Date:  July 1, 1993
Application Receipt Date:  August 19, 1993

PURPOSE

The National Institute of Child Health and Human Development (NICHD)
invites research grant applications for the support of investigations
into the basic cryobiology of mouse sperm, which may lead to improved
methods of cryopreservation of transgenic material in mouse sperm.  Two
NIH conferences have recommended that cryopreserved mouse sperm be
explored as a repository for transgenic material.

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), Transgenic Mouse Sperm Cryopreservation, is
related to the priority area of family planning.  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 202-783-3238).

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic for-profit and non-profit
organizations, public and private.  Minority individuals, persons with
disabilities, and women are encouraged to apply.

MECHANISM OF SUPPORT

This RFA will use the NIH individual research grant (R01).
Responsibility for the planning, direction, and execution of the
proposed project will be solely that of the applicant.  The total
project period for applications submitted in response to the present
RFA may not exceed five years.  The earliest expected award date is
April 1, 1994.

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.

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.

FUNDS AVAILABLE

It is expected that up to four new applications will be funded, within
the total cost limit of $400,000 available for the first year.  This
level of support is dependent on the receipt of a sufficient number of
applications of high scientific merit.  Although this program is
provided for in the financial plans of the NICHD, awards pursuant to
this RFA are contingent upon the availability of funds for this
purpose.

RESEARCH OBJECTIVES

Background

In recent years it has become possible to make specific additions or
alterations to the genetic material of organisms in order to study the
effect of the change on development, function, or evolution of disease
processes.  These changes can be maintained in vivo by propagating the
altered, so-called "transgenic," organisms.  The use of transgenic
animals to detect and manipulate key genes in mammalian development, as
well as those relevant to human diseases, has grown explosively with
the refinement and wide availability of the technology.  The mouse has
been the premier species, because of its well-characterized genetic
makeup and ease of use in the laboratory.  To date, the preservation of
most transgenic lines of mice has been done with cryopreserved mouse
embryos, or by maintaining breeding colonies of living transgenic mice.
However, these methods are expensive, labor-intensive, and/or
technically demanding.

An NICHD conference on "Transgenic Technology in  Medicine and
Agriculture" was held in December 1988.  A related conference was held
in November 1990 by the National Center for Research Resources (NCRR)
on "Development of Transgenic Animal Model Resources."  Both of these
conferences recommended the development of alternative strategies for
a repository of transgenic material.  Improved preservation of animal
genetic resources through cryopreservation was also recommended in the
1990 Report of the Committee on Preservation of Laboratory Animal
Resources, Institute of Laboratory Animal Resources, Commission of Life
Sciences, National Research Council.

A scientifically attractive and cost effective strategy is use of
cryopreserved sperm.  However, while cryopreservation techniques for
sperm have been used with some success for other mammalian species, for
example, the bovine, and to a degree, the human, the viability of mouse
sperm after cryopreservation is poor.  Some preliminary attempts using
empirical methods to cryopreserve mouse sperm have been made, but the
literature to date is contradictory.  Thus, this RFA is intended to
stimulate research in the basic cryobiology of mouse sperm, with
consequent development of cryopreservation methodology having a
rigorous scientific foundation.  The eventual benefit to the field and
to the public is anticipated to be the optimization of the procedures
necessary to generate a mouse sperm repository for preservation of
transgenic material.

Objecives

The long-term goal of this initiative is to support and encourage
research on improving the success and reliability of mouse sperm
cryopreservation.  It is generally agreed that an important approach to
this goal is to gain a better understanding of mouse sperm physiology
as it pertains to resistance to cryodamage.  Thus, it is the intent of
this RFA to support research on the basic cryobiology of mouse sperm,
with particular emphasis upon those physiological aspects that are
substantially related to the cryobiological properties of these cells.
Since there is a practical overall goal of this initiative, however, it
is expected that responsive applications would not only conduct
cryobiological experiments on mouse sperm but also conduct assessments
of viability and/or biological function.

For the purpose of this RFA, basic physiology of mouse sperm related to
cryobiology would include, but not be limited to, the following topics:

o  Osmotic and hydrologic properties
o  Membrane physiology
o  Organelle physiology
o  Intracellular biochemistry

as they apply to cryopreservation research.

Assessments of potentially enhanced viability and biological function
of thawed, cryopreserved, mouse sperm would include, but not be limited
to, the following monitoring parameters:

o  Acrosome reaction
o  Motility
o  Fertilizing ability
o  Pregnancy outcome
o  Chromosomal or genetic integrity

LETTER OF INTENT

Prospective applicants are strongly encouraged, but not required, to
submit, by July 1, 1993, 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 subsequent applications, the information
that it contains allows NICHD staff to estimate the potential review
workload and to avoid conflict of interest circumstances in the review
process.

The letter of intent is to be sent to Dr. Donna L. Vogel at the address
listed under INQURIES.

APPLICATION PROCEDURES

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 business offices; and from the Office of Grants
Inquiries, Division of Research Grants, National Institutes of Health,
Westwood Building, Room 449, Bethesda, MD 20892, telephone (301)
496-7441.

The RFA label available in the PHS 398 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 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:

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:

Susan Streufert, Ph.D.
Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03
Bethesda, MD  20892

Applications must be received by August 19, 1993.  If an application is
received after that date, it will be returned to the applicant.  The
Division of Research Grants (DRG) 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 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.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed by NICHD staff for
completeness and responsiveness.  Incomplete applications will be
returned to the applicant without further consideration.  If the
application is not responsive to the RFA, it will be returned to the
applicant, who may then submit it to DRG for review in competition with
unsolicited applications at the next available review cycle.

Responsive applications may be triaged by a peer review group to
determine their relative competitiveness.  The NIH will withdraw from
further competition those applications judged to be non-competitive for
award and notify the applicant Principal Investigator and institutional
official.  Those applications judged to be competitive will undergo
further evaluation for scientific merit.  Those applications that are
complete and responsive will be evaluated in accordance with the
criteria stated below for scientific/technical merit by an appropriate
peer review group convened by the NICHD.  The second level of review
will be provided by the National Advisory Child Health and Human
Development (NACHHD) Council.

Review criteria for RFAs are generally the same as those for
unsolicited research grant applications, including:

o  scientific, technical, or medical significance and originality of
proposed research;

o  appropriateness and adequacy of the experimental approach and
methodology proposed to carry out the research;

o  qualifications and research experience of the Principal Investigator
and staff, and of collaborators, if applicable;

o  adequacy of time and effort dedicated to the project;

o  availability of the resources necessary to perform the research;

o  appropriateness of the proposed budget and duration in relation to
the proposed research;

AWARD CRITERIA

The earliest anticipated date of award is April 1, 1994.  Funding
decision will be based on peer review and NACHHD Council
recommendations, program relevance, and availability of funds. In some
cases, if the proposed research has relevance to the research program
of the National Center for Research Resources (NCRR) as well as that of
the NICHD, the application may be dually assigned to, and considered
for funding by, the NCRR.  Any such assignment will be made
independently of peer review procedures.

INQUIRIES

Written and telephone inquiries concerning this RFA are encouraged.
The opportunity to clarify any issues or questions from potential
applicants is welcome.

Direct inquiries regarding scientific issues and address the letter of
intent to:

Donna L. Vogel, M.D., Ph.D
Center for Population Research
National Institute of Child Health and Human Development
Building 61E, Room 8B01
Bethesda, MD  20892
Telephone:  (301) 496-6515
FAX:  (301) 496-0962

Direct inquiries regarding fiscal matters to:

Melinda Nelson
Office of Grants and Contracts
National Institute of Child Health and Human Development
Building 61E, Room 8B17
Bethesda, MD  20892
Telephone:  (301) 496-5481

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance
No. 93.864, Population Research.  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 12374 or Health Systems Agency review.

.

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