MOUSE PHENOTYPING:  DEVELOPMENTAL AND FERTILITY DEFECTS

Release Date:  October 9, 2001

RFA:  RFA-HD-01-020

National Institute of Child Health and Human Development
 (http://www.nichd.nih.gov)

Letter of Intent Receipt Date:  February 11, 2002
Application Receipt Date:       March 13, 2002

PURPOSE

This Request for Applications (RFA) solicits applications to phenotype mutant 
mouse strains with developmental and fertility defects and to characterize 
the mutations responsible for their defects.  These projects should be 
designed to characterize mouse strains with defects in development and 
reproduction so as to isolate new alleles of known genes and identify new 
genes that are involved in the processes of development and fertility.  The 
mouse strains to be characterized should be obtained from existing mouse 
mutagenesis projects.  Appropriate sources of mutant strains include both 
small-scale mutagenesis projects and large-scale mutagenesis facilities, such 
as the NIH-funded mouse mutagenesis and phenotyping facilities at Baylor 
College of Medicine, Northwestern University, Jackson Laboratory, and the 
University of Tennessee.  Characterizing these mouse strains, and their 
mutations, is expected to help elucidate the basic cellular, molecular, and 
genetic mechanisms that direct embryonic and post-embryonic development, as 
well as yield insights into the mechanisms that control fertility.

These projects should identify and obtain mutant mouse strains with disrupted 
development and fertility, phenotype the strains to provide a detailed 
characterization of the defects, and characterize the mutations and the genes 
responsible for the defects.  The phenotypic characterization may also 
include high-throughput screens to identify a broad range of general features 
of these strains, where appropriate.  The detailed characterization should 
describe the specific cellular, molecular, and genetic features of the 
defects, whereas high-throughput screens, if included, should provide a 
general overview of the biological features of the animals with these 
defects.  Characterization of the mutations and genes should include analyses 
to increase the value of the mutants to the scientific community, such as 
genetic mapping to localize the mutations within the genome.

These projects will be part of NIH’s initiative to determine the function of 
mammalian genes.  Accordingly, their activities will be coordinated with 
related facilities, including the NIH-funded Mouse Mutagenesis and 
Phenotyping: Developmental Defects Facility at Baylor College of Medicine 
(http://www.mouse-genome.bcm.tmc.edu/ENU/MutagenesisProj.asp).  Additionally, 
the mutant strains, phenotypic and genetic information, protocols, assays, 
assessment criteria, and other materials and information generated by 
projects funded under this RFA will be made available to the wider biomedical 
community.  Further information about NIH initiatives on mouse genomics and 
genetics resources is available at http://www.nih.gov/science/mouse. 

HEALTHY PEOPLE 2010

The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS-
led national activity for setting priority areas.  This RFA is related to one 
or more priority areas.  Potential applicants may obtain "Healthy People 
2010" at http://www.health.gov/healthypeople/. 

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic, for-profit and non-profit 
organizations, public and private, such as universities, colleges, hospitals, 
and laboratories, units of State and local governments, and eligible agencies 
of the Federal government.  Applications will not be accepted from foreign 
institutions.  Racial/ethnic minority individuals, women, and persons with 
disabilities are encouraged to apply as Principal Investigators (PIs).

MECHANISM OF SUPPORT

This RFA will use the National Institutes of Health (NIH) Cooperative 
Research Project Grant (U01) award mechanism, an “assistance” mechanism 
(rather than an “acquisition” mechanism) in which substantial NIH scientific 
and/or programmatic involvement with the awardee is anticipated during 
performance of the activity.  Under the cooperative agreement, the NIH 
purpose is to support and stimulate the recipients’ activity by involvement 
in the activity and otherwise working jointly with the award recipients in a 
partner role, but it is not to assume direction, prime responsibility, or a 
dominant role in the activity.  Details of the responsibilities, 
relationships, and governance of the studies to be funded under cooperative 
agreements are discussed below under Terms and Conditions of Award.

This RFA is a one-time solicitation.  The earliest anticipated award date is 
September 30, 2002.

FUNDS AVAILABLE

The NICHD intends to commit approximately $3 million in total costs [direct 
plus Facilities and Administrative (F&A) costs] in FY 2002 to fund about four 
new grants in response to this RFA.  An applicant may request a project 
period of up to five years.  Because the nature and scope of the research 
proposed may vary, it is anticipated that the size of each award also will 
vary, with an average total cost of approximately $750,000 per year.  
However, in no case should total costs requested exceed $1.5 million per 
year.  Although the financial plans of the NICHD provide support for this 
program, awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of meritorious applications.
 
RESEARCH OBJECTIVES

Background

In 1998, the NIH convened a large group of distinguished scientists to 
recommend priorities for generating mouse genetic and genomic resources to 
help elucidate the genetic basis of human health and disease.  The 
recommendations included functional analyses of the mouse genome (see 
http://www.nih.gov/welcome/director/reports/mgenome.htm).  In response to 
this recommendation, 13 of the NIH institutes issued a pair of RFAs to 
support facilities to perform genome-wide mutagenesis and large-scale 
phenotyping of the resulting mutants.  Those RFAs led to the establishment of 
four mutagenesis and phenotyping facilities in 2000 and early 2001.  One is 
focused on developmental defects (Baylor College of Medicine) and three are 
focused on the nervous system and behavior (Northwestern University, 
University of Tennessee, and Jackson Laboratory).  Several other similar 
facilities are currently in operation and others will begin soon.  These 
facilities are producing a large number of mutant mouse strains that are 
providing new and critical insights into the mechanisms that govern normal 
and disrupted biological processes.  The projects to be funded by the current 
RFA will aid in characterizing the strains that display defects in 
development and in fertility regulation, and in identifying the mutations and 
the genes that control these processes.

Scope and Objectives

This RFA will support projects to phenotype mouse strains of utility for 
understanding embryonic development, post-embryonic development, and 
reproduction, and to characterize the mutations and the genes involved in 
these processes.  The scope of the proposed research may range from small 
projects that focus on the specific details of a few phenotypes to larger 
projects that examine many phenotypes and that characterize a broad range of 
features of those phenotypes.  Funded projects will make available obtained 
phenotypic and genetic data for wide distribution.  Additionally, they will 
make available mutant strains that are generated by the projects.  In 
particular, these projects will be required to:

o  Identify and obtain mutant mouse strains that are appropriate for studying 
embryonic and post-embryonic development and fertility regulation.  Include 
strains with mutations that are recessive and dominant, and viable and 
embryonic lethal, as appropriate.  These strains may be obtained from any 
appropriate source, including small-scale mutagenesis projects and large-
scale mutagenesis facilities, such as the four NIH-funded mouse mutagenesis 
and phenotyping facilities mentioned above.  Describe the source(s) of the 
mutant mouse strains to be used, justify their appropriateness for the 
proposed studies, and provide evidence of their availability.

o  Perform phenotypic analyses to identify and characterize developmental 
and/or fertility defects (see examples, below).  The goal of the 
characterization should be to elucidate the defect’s biological and genetic 
features.  The scope of projects may range from those designed to identify 
and examine a few categories of defects to those designed to identify and 
examine many categories of defects.  Additionally, projects may include high-
throughput phenotypic screens to identify and summarize a broad range of 
features of the mutant strains with developmental and/or fertility defects.  
If included, these screens should be designed to identify and characterize 
the developmental, reproductive, anatomical, cellular, physiological, 
molecular, genetic, metabolic, and/or pathological features of the mutants 
with the defects. 

o  Characterize the mutations by performing analyses that will make the 
mutants maximally useful to the scientific community.  Analyses should 
include rapid genetic mapping of the mutations to identify the region of the 
genome that contains the mutated genes, and other appropriate analyses of the 
mutations, genes, and gene products.

o  Develop and maintain a database including all of the phenotypic and 
mapping data on these mutant mice.

o  Propose a sharing plan to ensure that animals, preserved embryos/sperm, 
phenotyping assays, and phenotypic and genetic data for the mutant strains 
are widely available to the scientific community.  This plan should also 
address if, or how, the PI and grantee institution will exercise their 
intellectual property rights regarding patentable research resources.  These 
issues are addressed below under SPECIAL REQUIREMENTS.

o  The distribution plan must ensure that the mice, and their embryos and/or 
sperm, will be free from pathogens.

Projects should examine mutant mouse strains with defects in development 
and/or fertility.  Phenotypes of interest include, but are not limited to:

Developmental Defects:

o  Defects leading to embryonic lethality,

o  Patterning defects, such as alterations in the basic body plan, or absence 
or duplication of structures,

o  Alterations in organogenesis,

o  Alterations in growth rate,

Fertility Defects Resulting from Alterations in:

o  sex differentiation,

o  gametogenesis and gamete function,

o  development and function of the reproductive tract and gonads,

o  neuroendocrine control of reproduction,

o  neural mechanisms involved in mating behavior.

Guidance and Management Structure

The overall guidance and management of the program will be provided by a 
Steering Committee (SC).  The SC is the projects’ main governing committee 
and the committee through which the NIH interacts and collaborates with the 
projects.  It will consist of the PIs of each of the projects to be funded by 
this RFA, one or two NICHD Project Scientists, and a nonvoting, independent 
chairperson. 

Additional advice will be provided by the Mouse Genomics and Genetics 
Scientific Panel  (MSP), which will help integrate and coordinate the 
projects funded under this RFA with other related facilities.  It consists of 
about 10 scientists who are not affiliated with any of the projects.

SPECIAL REQUIREMENTS 

Meetings

PIs are expected to participate in two SC meetings annually, of two days 
duration each.  Budget requests should include travel funds for the PI and 
critical staff to attend those meetings in the Bethesda, MD area.

Milestones and Evaluations

Applications should define yearly milestones, which may be modified at the 
time of the award.  The awardee"s milestones will be provided to the SC.  It 
is expected that the milestones should be adjusted annually at the award 
anniversary date, both to incorporate the group"s scientific accomplishments 
and progress in the field in general, as well as to reflect the 
recommendations of the SC and the MSP.  In accordance with the procedure 
described under Terms and Conditions of Award, below, NICHD program staff may 
recommend augmenting any project, as discussed with the SC, or reducing or 
withholding funds if a project substantially fails to meet its milestones or 
to remain state-of-the-art.

Research Resources 

Restricted availability of unique research resources, upon which further 
studies are dependent, can impede the advancement of research.  The timely 
sharing of biomaterials, data, and software is an essential element of the 
rapid progress that has been made in the genetic analysis of mammalian 
genomes.  Accordingly, the NIH is interested in ensuring that the research 
resources developed by these projects become readily available to the broader 
research community in a timely manner for further research, development and 
application, in the expectation that this will lead to products and knowledge 
that benefit public health.  Resources to be shared will include biomaterials 
(pathogen-free mutant animals, preserved embryos and sperm), other patentable 
research resources (e.g., phenotyping assays, protocols, and 
instrumentation), and phenotypic and genetic data produced in projects funded 
by this RFA.  Additionally, NIH policy requires that investigators make 
unique research resources readily available for research purposes to 
qualified individuals within the scientific community when they have been 
published.

To address the joint interests of the government in the availability of, and 
access to, the results of publicly funded research, there are two special 
requirements regarding research resources produced in the applications 
submitted in response to this RFA:  (1) applicants are required to include a 
specific plan by which they will share research resources with the wider 
scientific community.  This plan must address if, and how, applicants will 
exercise their intellectual property rights while making available to the 
broader scientific community patentable research resources (e.g., mutant 
mice, phenotypic and genetic information, phenotyping assays, protocols, 
instrumentation, and methodologies), (2) NIH has made a Determination of 
Exceptional Circumstances (DEC) to eliminate the potential for patents on new 
mutant strains that are generated by this project and on newly identified 
uses of existing mutant strains.  These requirements are discussed below.

(1) Plan to Share Research Resources 

The plan to share research resources must make unique research resources 
readily available and accessible for research purposes to qualified 
individuals within the scientific community in accordance with the NIH Grants 
Policy Statement (see NIH Grants Policy Statement at 
http://grants.nih.gov/archive/grants/policy/nihgps_2001/index.htm and Principles and 
Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining 
and Disseminating Biomedical Research Resources at 
http://www.ott.nih.gov/policy/rt_guide_final.html).  These documents also 
define terms, parties, responsibilities, prescribe the order of disposition 
of rights, prescribe a chronology of reporting requirements, and delineate 
the basis for and extent of government actions to retain rights.  This plan 
should include an elaboration of the applicant"s anticipated plans to 
generate, or not generate, patents and/or exclusive or non-exclusive 
licensing of biomaterials and other patentable subject matter created in 
projects funded under this RFA.  This plan is also expected to include 
disclosure of any pre-existing intellectual property rights, including 
options to for-profit research sponsors, that are associated with 
biomaterials and data that may be generated.  Standard patent rights clauses 
may be found at 37 CFR Part 401.14 and are accessible from the Interagency 
Edison web page, http://www.iedison.gov.  Applicants are encouraged to 
discuss their plans for addressing this requirement with their institutional 
offices of technology transfer.

It is also expected that this plan will include all elements of the 
guidelines developed by the NIH and the Department of Energy (DOE) to address 
the special needs of genome research 
http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html. 

Where appropriate, the awardee may work with the private sector to make 
unique resources available to the wider biomedical research community at a 
reasonable cost.  Applicants may request funds to defray the costs of sharing 
resources, with adequate justification.

The Scientific Review Group will evaluate the adequacy of the proposed plan 
for sharing and data access.  NICHD program staff also will consider the 
adequacy of the plan when determining whether a grant shall be awarded.  The 
approved plan will become a condition of the award.  Progress Reports must 
contain information on activities for the sharing of research resources and 
intellectual property, if any.  Evaluation of any future renewal applications 
will include an assessment of the effectiveness of research resource release.

(2) Determination of Exceptional Circumstances 

NIH is interested in ensuring that the research resources developed through 
this RFA become readily available to the research community in accordance 
with the NIH Mouse Mutagenesis and Phenotyping Initiative.  To ensure 
unrestricted availability of mutant mice developed under this RFA, NIH has 
made a Determination of Exceptional Circumstances (DEC) pursuant to 37 C.F.R. 
401.3(a)(2) that covers mutant animals, embryos and sperm generated by the 
project, and newly identified uses of existing mutant strains.  The purpose 
of the DEC is to eliminate the potential for patents on mutant mice, embryos, 
sperm, and newly identified uses of existing mutant strains that could 
undermine the development of a widely available national resource that is the 
fundamental purpose of the NIH initiative to determine the function of 
mammalian genes.

Terms and Conditions of Award

The following Terms and Conditions will be incorporated into the award 
statement.  They are to be followed in addition to, and not in lieu of, 
otherwise applicable OMB administrative guidelines, HHS grant administration 
regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when state and 
local governments are eligible to apply), and other HHS, PHS, and NIH grant 
administration policies.

The administrative and funding instrument used for this program will be the 
U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in 
which substantial NIH scientific and/or programmatic involvement with the PI 
is anticipated during performance of the activities.  Under the cooperative 
agreement, the NIH purpose is to support and/or stimulate the PI"s activities 
by involvement in and otherwise working jointly with the PI in a partnership 
role, it is not to assume direction, prime responsibility, or a dominant role 
in the activities.  Consistent with this concept, the dominant role and prime 
responsibility resides with the PI for the project as a whole, although 
specific tasks and activities may be shared between the awardee and NIH 
program staff.  Facilities and administrative cost (indirect cost) award 
procedures apply to cooperative agreements in the same manner as for grants.  
Business management aspects of these awards will be administered by the NICHD 
Grants Management Branch in accordance with HHS, PHS, and NIH grant 
administrative requirements.

1.  Awardee Rights and Responsibilities

The PI will coordinate project activities scientifically and administratively 
at the awardee institution and at other sites that may be supported by 
subawards to this award.  The PI will have the primary responsibility for 
defining the details for the project within the guidelines of this RFA, and 
for performing the scientific activities.  The PI will agree to accept close 
coordination, cooperation, and participation of the NICHD Project Scientist, 
the Steering Committee (SC) and the Mouse Genomics and Genetics Scientific 
Panel (MSP) in those aspects of scientific and technical management of the 
project described under "Project Scientist Responsibilities," "Steering 
Committee Functions," and " Mouse Genomics and Genetics Scientific Panel 
Functions" (below).  Specifically, the PI will:

o  Determine experimental approaches, design protocols, direct experiments, 
and set project milestones, in consultation with NICHD program staff and the 
SC,

o  Implement approved plans for sharing research resources,

o  Submit periodic progress reports in a standard format, as agreed upon by 
the SC,

o  Present results and plans at SC meetings,

o  Accept and implement the common guidelines and procedures approved by the 
SC and the MSP,

o  Solicit the views of the broad biomedical research community for the 
phenotypes and/or genotypes of interest,

o  Release data and publish results, as agreed upon by NICHD program staff 
and the SC.

2.  NICHD Responsibilities

NICHD Project Scientist:

The NICHD Project Scientist(s) will be staff member(s) of the Developmental 
Biology, Genetics and Teratology Branch and/or the Reproductive Sciences 
Branch.  They will have substantial scientific/programming involvement that 
includes facilitating the partnership between NIH and the phenotyping 
projects, helping to balance the projects’ activities with new and emerging 
research opportunities, and ensuring that the projects’ activities are 
consistent with the mission of NICHD.  They will help to maintain scientific 
balance between accomplishing goals and addressing emerging research 
opportunities.  The role of the NICHD Project Scientist will be to 
facilitate, but not to direct activities.  It is anticipated that decisions 
will be reached by consensus with the PI through the SC.  One or two Project 
Scientists will participate as members of the SC.  NICHD staff will have a 
total of one vote.  The NICHD Project Scientist(s) will:

o  Provide relevant expertise and overall knowledge,

o  Provide information about ongoing NIH-supported research and resource 
collections,

o  Attend SC meetings as one voting member and participate with other SC 
members in the group process of setting research priorities, deciding optimal 
research approaches and protocol designs, and contributing to the adjustment 
of research protocols or approaches as warranted. The Project Scientist(s) 
will assist and facilitate the group process and not direct it.  They will 
help develop operating guidelines, quality control procedures, and consistent 
policies for dealing with situations that require coordinated action.  The 
Project Scientist(s) must be informed of all major interactions of SC 
members,

o  Serve as liaison to the MSP, attend MSP meetings as a non-voting member to 
help coordinate the activities of the projects with those of other NIH 
mutagenesis and phenotyping projects, and with other NIH mouse genomics and 
genetics initiatives.  The Project Scientist will also coordinate the 
activities of projects funded under this RFA with other US and international 
efforts,

o  Serve as liaison between the grantees and the other NIH program staff,

o  Coordinate the projects’ activities with NIH-funded repositories and 
databases, to ensure the rapid and efficient distribution and long-term 
storage of biomaterials and data,

o  Assist in developing timetables for, and facilitating, the timely and wide 
distribution of biomaterials and data to the biomedical community,

o  Participate in data analysis, interpretations and, where warranted, co-
author publications that report results of studies performed under this RFA.

NICHD Project Officer:

The NICHD will appoint a Project Officer, apart from the Project Scientist, 
who will:

o  carry out continuous review of all activities to ensure that the objective 
are being met and that all regulatory, fiscal, and administrative matters are 
handled according to NIH guidelines.

o  have the option to withhold support to a participating institution if 
technical performance requirements are not met.

o  Perform other duties normally required for program stewardship of grants.

3. Collaborative Responsibilities

Steering Committee Functions:

The Steering Committee (SC) will be the main governing body of the projects 
to be funded by this RFA.  It will oversee and coordinate interactions among 
the projects, and will mediate interactions between the projects and the NIH.  
The SC will discuss scientific goals and progress, and recommend how mutant 
strains should be obtained, analyzed, and shared in order to be maximally 
valuable to all interested investigators.  It will help to monitor the plans 
for sharing research resources.  It will also address the recommendations 
made by the MSP.  The SC will consist of the PIs of each of the projects, one 
or two NICHD Project Scientists, and a nonvoting independent chairperson.  
Each PI will have one vote and the NIH Project Scientist(s) will have a total 
of one vote.

Mouse Genomics and Genetics Scientific Panel (MSP) Functions:

The MSP coordinates activities among the projects, facilities and resources 
participating in NIH"s mouse mutagenesis and phenotyping initiative, 
including those to be funded in response to this RFA.  The MSP uses its 
knowledge of the activities of all of the participating projects to ensure 
adequate investigation, communication and sharing, and to avoid redundant 
activities.  It helps to coordinate activities that involve the mutagenesis, 
phenotyping, mapping, maintenance, and distribution and sharing of mutant 
mouse strains.  The MSP evaluates and makes recommendations regarding the 
coordination of the activities of the projects that are funded by the 
mutagenesis and phenotyping initiatives, and other related activities that 
may be developed in the future. 

The MSP’s responsibilities include making recommendations that lead to 
exchanging mutants among the projects, sharing assay strategies, adopting 
common policies on data sharing, creating compatible databases, and other 
activities that will make these facilities of maximal utility to the 
scientific community.  The MSP also sets standards for data format and 
nomenclature, as well as developing common guidelines and procedures for 
deposition of the primary phenotypic data, and for the preservation of mutant 
mouse strains.

The committee consists of about 10 scientists who are not affiliated with any 
of the mutagenesis and phenotyping projects, and are not members of the 
advisory committees of those projects.  Collectively, they have broad 
expertise in relevant topics such as developmental biology, reproduction, 
neurobiology, behavior, mutagenesis, phenotyping, mouse genetics, husbandry, 
genomics, and databases issues.  The NIH Project Scientist(s) attend the MSP 
as non-voting members and act as a representative of the SC.   The MSP meets 
at least once each year. 

4.  Arbitration Process

Any disagreements that may arise in scientific or programmatic matters within 
the scope of the award between grantees and the NIH may be brought to 
arbitration.  This special arbitration procedure in no way affects the 
awardee"s right to appeal an adverse action that is otherwise appealable in 
accordance with PHS regulations 42 CFR Part 50, Subpart D, and HHS regulation 
at 45 CFR Part 16.  An Arbitration Panel will help resolve both scientific 
and programmatic issues that develop during the course of work that restrict 
progress.  The Arbitration Panel will be composed of three members:  a 
designee of the SC chosen without the NIH staff voting, one NIH designee, and 
a third designee with expertise in the relevant area who is chosen by the 
other two members.

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, Internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to review the Internet sites.  Reviewers are cautioned that their anonymity 
may be compromised when they directly access an Internet site.

PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT

The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at:  
http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. 

Applicants may wish to place data collected under this RFA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application.  In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

LETTER OF INTENT

Prospective applicants are asked to submit a letter of intent that includes a 
descriptive title of the proposed research, the name, address, telephone 
number, and e-mail address of the Principal Investigator, the identities of 
other key personnel and participating institutions, and the number and title 
of this RFA.  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 allows NICHD staff to estimate the potential 
review workload and plan the review.

The letter of intent is to be sent to Dr. Steven Klein, at the address listed 
under INQUIRIES, below, by February 11, 2002.

APPLICATION PROCEDURES

The PHS 398 research grant application instructions and forms (rev. 5/2001) 
at http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in 
applying for these grants. This version of the PHS 398 is available in an 
interactive, searchable PDF format.  Beginning January 10, 2002, the NIH will 
return applications that are not submitted on the 5/2001 version.  For 
further assistance contact GrantsInfo, Telephone 301-435-0714, Email: 
GrantsInfo@nih.gov. 

Application Instructions

Applicants must describe the project in the Research Plan section of the 
application within the normal page limitation (25 pages).  The application’s 
Research Plan must include sections on:  (1) overall purpose, strategy and 
plans, (2) phenotyping, (3) characterizing the mutations and the genes, (4) 
database/ bioinformatics, and (5) procedures for sharing research resources, 
including plans to exercise, or not to exercise, intellectual property rights 
(see SPECIAL REQUIREMENTS, above).  However, if necessary, you may use up to 
five additional pages to describe the procedures for sharing mice, and 
phenotypic and genetic data (sections 4 and 5).  This exception is made to 
enable a more complete description of these components, which are critical to 
the goals of this RFA.

For the purpose of accomplishing the goals of this RFA, the project may 
include investigators at more than one site, and subcontracts may be included 
in the budget to support investigators at sites other than the awardee 
institution.  Applications should define yearly milestones, which may be 
modified at the time of award.  Budget requests should include travel funds 
for the PI and other critical staff to attend the SC meetings in the 
Bethesda, MD area twice per year.

Submission Instructions

The RFA label available in the PHS 398 (rev. 5/01) application form must be 
stapled to the bottom of the face page of the application and must display 
the RFA number, HD-01-020.   A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note this 
is the pdf format.  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 should be 
sent to:

Director, Division of Scientific Review
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 5E03F, MSC 7510
Bethesda, MD  20892-7510
Rockville, MD  20852  (for express/courier service)

Applications must be received by March 13, 2002.  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 RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  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 CSR, and for 
responsiveness to this RFA by NICHD.  Incomplete and/or nonresponsive 
applications will be returned to the applicant without further consideration.  
Applications that are complete and responsive will be evaluated for 
scientific and technical merit by an appropriate peer review group convened 
by NICHD, in accordance with the review criteria stated below.  These reviews 
will not include site visits.  As part of the initial merit review, all 
applications will receive a written critique and may undergo a process in 
which only those applications deemed to have the highest scientific merit 
will be discussed, assigned a priority score, and receive a second level 
review by the National Advisory Child Health and Human Development Council.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance 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 
research 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.

o  Significance:  What will be the expected impact of the phenotypic and 
mapping information produced by the project on our understanding of the 
genetic bases of development and reproduction? 

o  Approach:  Does this study specify methodologies for phenotyping the 
mutants and for characterizing the mutations responsible for their defects?  
Is the conceptual framework for conducting phenotyping and mapping adequately 
developed, well integrated, and appropriate to the aims of the project?  Will 
the proposed strategies enable identification of both dominant and recessive 
mutations that alter the processes of development and/or fertility?  Does the 
applicant acknowledge potential problem areas and consider alternative 
tactics?

o  Innovation:  Does the project employ novel concepts, approaches or 
methods?  Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?

o  Investigator:  Is the investigator 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)?

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

Reviewers will also evaluate:

o  the response to the Research Objectives described above,

o  Integration with other resources:  Are the plans adequate to ensure that 
the project will be able to obtain appropriate mutant strains?  Are the plans 
adequate to integrate the mutants and the phenotypic data with those 
collected in other comparable projects?  

o  Exportability and Accessibility:  What is the likelihood that the mutant 
mouse strains developed and/or used in the project will be made widely 
available in a timely fashion to the scientific community?  What is the 
likelihood that patentable research results, such as phenotypic and mapping 
information and methodologies, will be widely available for the scientific 
community, given the proposed plan to exercise, or not to exercise, 
intellectual property rights on those products?  Does the project specify 
plans for creation of a highly efficient and organized bioinformatics 
database?  Do the investigator"s quality control plans assure that databases 
provided to the wider scientific community will be accurate and highly 
efficient?

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:  February 11, 2002
Application Receipt Date:       March 13, 2002
Peer Review Date:               June 2002
Advisory Council Date:          September 2002
Earliest Award Date:            September 30, 2002

AWARD CRITERIA

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

o  Scientific and technical merit of the proposed project as determined by 
peer review,

o  Cost effectiveness of the proposed strategy,

o  Promise of the proposed project to accomplish the goals of this RFA,

o Geographical distribution of projects,

o  Availability of funds.

INQUIRIES

Inquiries concerning this RFA are strongly encouraged.  NICHD staff welcomes 
the opportunity to clarify issues or questions from potential applicants.  
Direct inquiries regarding programmatic issues to:

Dr. Steven Klein
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:  301-480-0303
E-mail:  kleins@exchange.nih.gov 

Dr. Tracy L. Rankin
Reproductive Sciences Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8B01, MSC 7510
Bethesda, MD  20892-7510
Telephone:  301-435-6979
Fax:  301-480-2389
E-mail:  tr44x@nih.gov 

Direct inquiries regarding fiscal matters to:

Mr. Chris Myers
Grants Management Branch
National Institute of Child Health and Human Development
6100 Executive Boulevard, Room 8A17, MSC 7510
Bethesda, MD  20892-37510
Telephone:  301-435-6996
E-mail:  myersc@exchange.nih.gov 

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.864 and 93.865.  Awards are made under authorization of Sections 301 and 
405 of the Public Health Service Act as amended (42 USC 241 and 284) and 
administered under NIH grants policies and Federal Regulations 42 CFR 52 and 
45 CFR Parts 74 and 92.  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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