DEVELOPING THE POTENTIAL OF XENOPUS TROPICALIS AS A GENETIC MODEL

Release Date:  January 31, 2001

RFA:  RFA-HD-01-008

Trans-NIH Xenopus Working Group
 (http://www.nih.gov/science/models/xenopus)
National Institute of Child Health and Human Development, NICHD
 (http://www.nichd.nih.gov/)
National Institute of Neurological Disorders and Stroke, NINDS
 (http://www.ninds.nih.gov/)
National Institute of Environmental Health Sciences, NIEHS
 (http://www.niehs.nih.gov/)
National Institute of General Medical Sciences, NIGMS
 (http://www.nigms.nih.gov/)
National Institute of Mental Health, NIMH
 (http://www.nimh.nih.gov/)

Letter of Intent Receipt Date:  May 16, 2001
Application Receipt Date:       July 11, 2001

THIS RFA USES THE "MODULAR GRANT" AND "JUST-IN-TIME" CONCEPTS.  IT INCLUDES 
DETAILED MODIFICATIONS TO STANDARD APPLICATION INSTRUCTIONS THAT MUST BE USED 
WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS RFA.

PURPOSE

This Request for Applications (RFA) solicits research grant applications to 
examine the feasibility of using Xenopus tropicalis for standard genetic 
manipulations.  The research proposed should optimize the conditions required 
to perform efficient, large-scale mutagenesis, and should use the optimized 
parameters to perform small-scale mutagenesis; phenotyping; and gene cloning, 
identification, and characterization.  Mutant animals, protocols, and data 
produced by these projects should be made available to the scientific 
community.  We anticipate that the mutants, data and procedures developed by 
the projects funded under this RFA will enable Xenopus tropicalis to play a 
significant role in identifying and characterizing genes that regulate 
cellular and developmental processes.

Over the past few years, the National Institutes of Health (NIH) has asked a 
broad representation of the biomedical research community to recommend which 
non-mammalian models would help to elucidate the bases of human health and 
disease.  The community has repeatedly recommended that Xenopus be a component 
of the NIH strategy.  For example, Xenopus was one of the five models 
highlighted at the NIH Non-Mammalian Models Meeting in 1999. The NIH responded 
to the community’s recommendations by establishing the Trans-NIH Xenopus 
Initiative.  Development of the X. tropicalis system has been one of the 
community’s highest priorities.  Accordingly, this RFA is a major component of 
the NIH Xenopus initiative.  The entire initiative is described on the NIH 
Xenopus Website (http://www.nih.gov/science/models/xenopus).

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 Request for Applications (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 and foreign, for-profit and non-
profit organizations, public and private, such as universities, colleges, 
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) Individual Research 
Project Grant (R01) award mechanism.  Responsibility for the planning, 
direction, and execution of the proposed project will be solely that of the 
applicant.  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 anticipated award date is April 1, 2002.

Specific application instructions have been modified to reflect “MODULAR 
GRANT” and “JUST-IN-TIME” streamlining efforts being examined by the NIH.  
Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm. 

FUNDS AVAILABLE

The participating Institutes intend to commit up to approximately $2.25 
million in total costs [direct plus Facilities and Administrative (F&A) costs] 
in FY 2002 to fund up to six new grants in response to this RFA.  An applicant 
may request a project period of up to five years and a budget for direct costs 
of up to $250,000 per year. Because the nature and scope of the research 
proposed may vary, it is anticipated that the size of each award also will 
vary.  Although this program is provided for in the financial plans of the 
participating Institutes, 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

The NIH is interested in helping to develop and support tools and resources to 
improve the ability of model organisms to elucidate the genetic mechanisms 
that regulate normal and abnormal biological processes.  To accomplish this 
goal, the NIH has held a series of workshops at which a broad representation 
of the biomedical research community provided advice and recommendations.  The 
workshops’ participants recommended which animal models were most likely to 
provide insights into biological processes, and which tools and resources 
would improve the ability of those models to make significant contributions to 
biomedical research.  The NIH progress and plans for implementing the 
community’s recommendations are described on the NIH Model Organism Website 
(http://www.nih.gov/science/models/).  This RFA solicits applications to 
develop critical research tools and resources for one of the animal models, 
the amphibian, Xenopus tropicalis.

The amphibian has a long and illustrious history as a major model system for 
elucidating cellular and developmental processes.  For the past few decades, 
Xenopus laevis has been the predominant amphibian used because it possesses 
many unique advantages.  These advantages include the production of large 
embryos in large numbers, external development, and rapid development.  The 
embryos also recover well from experimental manipulations, and their cells and 
identified regions can be excised and cultured in a simple salt solution.  
These advantages have enabled Xenopus to clarify two areas of vertebrate 
biology:  embryonic development and cell biological processes. In the former 
area, Xenopus has led the way in identifying the mechanisms of early fate 
decisions, patterning the basic body plan, organogenesis, and signaling 
pathways in development.  Contributions to cell biology and biochemistry 
include seminal work on chromosome replication, chromatin and nuclear 
assembly, cell cycle components, cytoskeletal elements, and intercellular and 
intracellular signaling pathways.  In addition, Xenopus is well suited to 
identify novel expressed genes that regulate developmental processes, and it 
has been widely utilized to characterize the activities of genes that are 
broadly expressed across vertebrates.  Xenopus’ advantages and wealth of 
research findings have been combined with molecular techniques, such as in 
situ hybridization, antisense oligonucleotides, dominant negative proteins, 
and expression cloning.  These advantages, findings, and techniques make 
Xenopus laevis an important model for elucidating the cellular and molecular 
mechanisms that control much of vertebrate biology.  

Despite Xenopus’ advantages for cellular and molecular studies, it has not 
been used for classical genetic studies because the species of the Xenopus 
genus that has been used by researchers, X. laevis, is pseudotetraploid and 
has a long generation time (one – two years).  However, several years ago 
researchers began examining the related diploid species, X. tropicalis, which 
has a short generation time (three – five months).  X. tropicalis maintains 
the advantages of X. laevis and has performed successfully in preliminary 
genetic studies.  Additionally, it shows a high degree of sequence similarity 
and functional interchangeability with X. laevis.  Thus, procedures, probes, 
and reagents developed in one species can be used in the other species.  
However, detailed examinations must be performed to establish that X. 
tropicalis is amenable to genetic manipulations such as insertional and 
chemical mutagenesis, and to optimize these procedures.

This RFA solicits projects to optimize the procedures to mutagenize and 
phenotype X. tropicalis, and to create and characterize mutants with 
interesting phenotypes.  The mutants, data, and procedures developed by these 
projects will enable X. tropicalis to play a significant role in identifying 
and characterizing genes that regulate cellular and developmental processes.   
Additionally, verification that X. tropicalis is amenable to genetic 
manipulations will lead to large-scale mutagenesis and phenotyping projects; 
to the production of resources for gene mapping, such as PACs, BACs, and 
radiation hybrid panels; and, ultimately, to sequencing the X. tropicalis 
genome.  These genetic resources will enable X. tropicalis to become an 
extremely important model for studying developmental and cell biological 
processes because they will enable researchers to examine the cellular, 
molecular, and genetic aspects of a process in a single model.  Information 
generated by these studies will be of great benefit to the entire biomedical 
research community. 

Scope

Projects sought by this RFA should optimize the methodologies required to use 
X. tropicalis in large-scale screens and should perform preliminary studies 
using the optimized procedures.  Each project should be designed to identify 
the optimal parameters required to perform mutagenesis and should perform 
pilot screens using the optimized parameters.  The pilot analyses should 
develop and use breeding and screening strategies to identify and characterize 
a limited number of mutants.  The strategies may include the use of haploids 
and gynogenic diploids, and projects may include aims to optimize techniques 
to generate these animals.  Interesting mutants should be used to clone, 
identify, and characterize the mutant genes.  Additionally, the project should 
devise and implement mechanisms to share with the biomedical research 
community the methodologies, genetic and phenotypic data, and the mutants.

Projects may propose to use any methodology to generate mutations.  Examples 
of relevant projects include, but are not limited to, those that perform: 

Insertional Mutagenesis

Optimize the procedures required to perform efficient insertional mutagenesis 
to achieve a high rate of integration and long-term transgenic viability.  
Examples of strategies include gene traps, enhancer traps, and insertion of 
retroviruses.  Use the optimized mutagenesis protocols to identify and 
characterize interesting mutants.  Develop breeding and screening strategies 
to reveal insertions in different types of genes, such as recessive genes, 
essential genes, maternal effect genes, and genes that are expressed in 
particular spatial and temporal patterns.  Clone, identify, and characterize 
the mutated genes.
	
Chemical Mutagenesis

Identify the most efficient means to perform chemical mutagenesis by 
optimizing the relevant parameters such as mutagen dose and exposure duration.  
Perform chemical mutagenesis on a limited scale.  Develop breeding and 
screening strategies to identify dominant and recessive mutations.  Devise and 
perform phenotypic screens to identify mutants with interesting phenotypes, 
such as those described below.  Develop procedures to characterize mutants 
with interesting phenotypes.  Devise and perform assays, such as expression 
cloning, to clone and identify the mutations.  The goal should be to optimize 
the procedures for mutagenesis and phenotyping, and to perform limited 
mutagenesis, phenotyping, and gene identification, not to perform saturation 
mutagenesis.

Phenotypes of interest include:

o Alterations in embryonic patterning;

o Alterations in organogenesis and organ function;

o Alterations in limb formation and patterning;

o Alterations in the expression pattern of known genes;

o Alterations in nervous system development and function, and potential models 
of neurological disorders;

o Alterations in toxicity (due to environmental/industrial chemicals/agents).

SPECIAL REQUIREMENTS

Four additional areas must be addressed in the application.  These are 
described in the following sections.

Research Resources

Restricted availability of unique research resources, upon which further 
studies are dependent, can impede the advancement of research.  The sharing of 
biomaterials, data, and software in a timely manner, on the other hand, has 
been an essential element in the rapid progress that has been made in the 
genetic analysis of mammalian genomes.  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 [NIH Grants Policy Statement 
(http://grants.nih.gov/grants/policy/nihgps); Principles and Guidelines for 
Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating 
Biomedical Research Resources: Final Notice, December 1999 
(http://www.nih.gov/od/ott/RTguide_final.htm)].  Biomaterials (e.g., 
transgenic and mutant animals, preserved sperm and embryos) and other 
patentable research resources (e.g., mutagenesis protocols, and genetic and 
phenotypic data for all mutant strains) produced in projects funded by this 
RFA are expected to be made available and distributed to the broader 
scientific community.

The NIH is interested in ensuring that the research resources developed 
through this RFA become readily available to the research community for 
further research, development, and application, in the expectation that this 
will lead to products and knowledge of benefit to the public.  For this 
reason, NIH is concerned that patents on mutant embryos and sperm, mutagenesis 
protocols, and genetic and phenotypic data for all mutant strains and other 
research resources might have a chilling effect on the future development of 
products and information that may improve the public health.  At the same 
time, NIH recognizes the rights of grantees to elect and retain title to 
subject inventions developed under Federal funding under the provision of the 
Bayh-Dole Act.

For applications submitted in response to this RFA, there are two special 
requirements regarding research resources produced in the proposed project:

(1) Applicants must include a specific plan by which they will share research 
resources with the wider scientific community. 

(2) Applicants must include a plan addressing if, or how, they will exercise 
their intellectual property rights while making available to the broader 
scientific community patentable research resources (e.g., transgenic and 
mutant animals, mutagenesis protocols, and genetic and phenotypic data for all 
mutant strains).  

Applicants are encouraged to discuss their proposed plans for addressing these 
requirements with their institutional offices of technology transfer.  Each of 
the two requirements is discussed in detail below. 

Plan to Share Research Resources: 

To address the joint interests of the government in the availability of, and 
access to, the results of publicly funded research, NIH requires applicants 
who respond to this RFA to propose detailed plans for sharing the research 
resources generated through the grant.  The resources to be shared include all 
materials developed in projects funded under the RFA, including, but not 
limited to, mutant animals, mutagenesis protocols, and genetic and phenotypic 
data for all mutant strains.  For this purpose, it is the opinion of NIH that 
dissemination of such data and materials via individual laboratories and 
Internet sites is not sufficient, as it would force interested investigators 
to search several different data collections to make use of the results of 
this initiative.  It is preferable that data, protocols, technologies, and 
biomaterials generated with grants funded under this RFA be placed in common, 
public repositories and databases that are widely accessible by investigators 
in the scientific community. 

Your data and biomaterials sharing plan should include each of the following 
components: 

(1) A plan to establish and make available a comprehensive database containing 
detailed results from the phenotypic screens; (2) a plan to make the data 
available to an appropriate centralized database when one becomes available; 
(3) a plan to make available the methodologies used to perform the mutagenesis 
and the phenotypic screens; (4) a plan to make available transgenic and mutant 
animals (including their embryos, oocytes, and sperm) with a) phenotypes that 
are not of interest to investigators associated with your project, and b) 
phenotypes that are of interest to investigators associated with your project; 
(5) a plan to make the transgenic and mutant animals identified in 4a and 4b 
available to an appropriate centralized stock center when one becomes 
available; (6) a distribution timeline.

The scientific review group will evaluate the adequacy of the proposed plan 
for sharing and data access.  Comments on the plan and any concerns will be 
presented in an administrative note in the summary statement.  The adequacy of 
the plan will be considered by NIH program staff and will be important in 
determining whether the grant will be awarded. The sharing plan as approved, 
after negotiation with the applicant when necessary, will be a condition of 
the award.  Evaluation of non-competing continuation applications will include 
assessment of the effectiveness of research resource release.

Intellectual Property Rights: 

NIH is interested in ensuring that the research resources developed through 
this RFA become readily available to the research community. 
 
With regard to patentable research results, such as methodologies, transgenic 
and mutant animals identified through genetic and phenotypic screens, embryos, 
oocytes and sperm for these mutants, and genetic and phenotypic data for all 
mutant strains, the NIH requires applicants who respond to this RFA to develop 
a plan addressing if, or how, they will exercise their intellectual property 
rights while making available to the broader scientific community research 
resources produced in projects funded under this RFA.  This is expected to 
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 agreements involving intellectual property rights, including options 
to for-profit research sponsors that are associated with biomaterials and data 
that may be generated. The requirement for this plan is in addition to the 
requirement for the plan for sharing and disseminating research resources 
described in the previous section.  

The scientific review group will evaluate the adequacy of the proposed plan 
for handling intellectual property rights.  Comments on the plan and any 
concerns will be presented in an administrative note in the summary statement.  
The adequacy of the proposed plan will be considered by NIH program staff to 
determine whether the grant shall be awarded. The plan as approved, after 
negotiation with the applicant when necessary, will be a condition of the 
award.  Evaluation of non-competing continuation applications will include 
assessment of the awardee’s adherence to the proposed plan.

Applicants also are reminded that the grantee institution is required to 
disclose each subject invention to NIH within two months after the inventor 
discloses it in writing to grantee institutional personnel responsible for 
patent matters. The awarding Institutes reserve the right to monitor awardee 
activity in this area to ascertain if patents or patent applications on 
mutants identified through genetic and phenotypic screens, embryos and sperm 
for these mutants, genetic and phenotypic screens, mutagenesis protocols, and 
genetic and phenotypic data for all mutant strains or other patentable subject 
matter are adversely affecting the goals of this RFA.

Principles and guidelines for recipients of NIH research grants on obtaining 
and disseminating biomedical research resources can be found at 
http://www.nih.gov/od/ott/RTguide_final.htm. 

Additional Requirements

o During the course of the award period, the Principal Investigators will be 
required to meet with NIH staff to review and share scientific progress.  
Other scientists external to and knowledgeable about these studies also may be 
invited to participate.  Application budget requests should include travel 
funds for the Principal Investigator to attend annual meetings in the 
metropolitan Washington, D.C. area.  Principal Investigators are also 
encouraged to plan periodic meetings to exchange information with one another.  
The funding for those meetings should come from other sources.

o Propose a strategy to enable your project to interact with the other 
projects funded under this RFA.  This strategy should include procedures to 
make your results, progress, and plans available to the other projects, and 
procedures to keep you informed of the results, progress, and plans of the 
other projects.  Examples include web sites, newsletters and other 
communications.  These proposals will form the basis for the development of 
procedures to ensure that these projects interact. 

URLS IN NIH GRANT APPLICATIONS OR APPENDICES

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

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, and telephone 
number 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 NIH staff to estimate the potential review workload and plan 
the review.

Send the letter of intent to Dr. Steven Klein, at the address listed under 
INQUIRIES, below, by May 16, 2001.

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, on the Internet at 
http://grants.nih.gov/grants/funding/phs398/phs398.html, 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, E-mail:  Grantsinfo@nih.gov.     

Application Instructions 

The modular grant concept establishes specific modules in which direct costs 
may be requested as well as a maximum level for requested budgets. Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only when 
there is a possibility for an award. It is anticipated that these changes will 
reduce the administrative burden for the applicants, reviewers and Institute 
staff.  The research grant application form PHS 398 (rev. 4/98) is to be used 
in applying for these grants, with the modifications noted below.

Modular Grant applications will request direct costs in $25,000 modules, up to 
a total direct cost request of $250,000 per year.  The total direct costs must 
be requested in accordance with the program guidelines and the modifications 
made to the standard PHS 398 application instructions described below:

o FACE PAGE:  Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total 
Direct plus Facilities and Administrative  (F&A) costs] for the initial budget 
period.   Items 8a and 8b should be completed indicating the Direct and Total 
Costs for the entire proposed period of support, identical to the figures in 
Items 7a and 7b for this RFA.

o DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD:  Do not complete Form Page 
4 of the PHS 398.  It is not required and will not be accepted with the 
application.

o BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT:  Do not complete the 
categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION:  Prepare a Modular Grant Budget Narrative 
page. (See http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages.)  At the top of the page, enter the total direct costs requested for 
the project year.  This is not a Form Page.

o Under Personnel, list ALL project personnel, including their names, percent 
of effort, and roles on the project.  No individual salary information should 
be provided.  However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (direct 
plus F & A), rounded to the nearest $1,000.  List the 
individuals/organizations with whom consortium or contractual arrangements 
have been made, the percent effort of all personnel, and the role on the 
project.  Indicate whether the collaborating institution is foreign or 
domestic.  The total cost for a consortium/contractual arrangement is included 
in the overall requested modular direct cost amount.  Include the Letter of 
Intent to establish a consortium.

o BIOGRAPHICAL SKETCH:  The Biographical Sketch provides information used by  
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three 
pages may be used for each person.  A sample biographical sketch may be viewed 
at: http://grants.nih.gov/grants/funding/modular/modular.htm.   

- Complete the educational block at the top of the form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years;
- List selected peer-reviewed publications, with full citations.

o CHECKLIST:  This page should be completed and submitted with the 
application.  If the F&A rate agreement has been established, indicate the 
type of agreement and the date.  All appropriate exclusions must be applied in 
the calculation of the F&A costs for the budget period.

o The applicant should provide the name and telephone number of the individual 
to contact concerning fiscal and administrative issues if additional 
information is necessary following the initial review.

Submission Instructions  

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
stapled to the bottom of the face page of the application and must display the 
RFA number HD-01-008.  A sample RFA label is available at 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf.  Please note this is 
in 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 five 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)

Applications must be received by July 11, 2001.  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.  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 
for responsiveness to the RFA by NICHD.  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 CSR in accordance with the review criteria stated below.  As part of the 
initial merit review, all applications will 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 appropriate National Advisory Councils or Boards.

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.

(1) Significance:  What is the expected impact of the proposed mutagenesis, 
breeding and screening strategies on the use of Xenopus to study biological 
processes?  Will the mutants produced by this project be useful for studying 
biological processes?

(2) Approach:  Are the conceptual framework, design, methods, and analyses 
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:  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?

(4) 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)?

(5) 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?

In addition, applications responding to this RFA will be assessed with respect 
to the following criteria.  This evaluation will be presented in an 
administrative note in the summary statement, and will not factor into the 
numerical score:

o Exportability and accessibility:  What is the likelihood that the transgenic 
and mutant animals, and the phenotypic information generated by the project 
will be made widely available in a timely fashion to the scientific community?  
What is the likelihood that patentable research results will be widely 
available to the scientific community, given the proposed plan to exercise (or 
not to exercise) intellectual property rights regarding transgenic animals, 
mutant animals, embryos and sperm for these animals, mutagenesis protocols, 
and genetic and phenotypic data?

o Adequacy of the plan to share research resources and the plan to exercise 
(or not exercise) intellectual property rights regarding patentable research 
resources.  

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:    May 16, 2001 
Application Receipt Date:         July 11, 2001
Peer Review Date:                 November 2001
Council Review:                   January 2002
Earliest Anticipated Start Date:  April 2002

AWARD CRITERIA

Criteria that will be used to make award decisions include:

o Scientific and technical merit of the proposed project as determined by peer 
review;
o Cost effectiveness of the proposed strategy;
o Adequacy of plans to make widely available to the research community all 
research resources developed during this project;
o Adequacy of plans to exercise (or not exercise) intellectual property rights 
while permitting wide availability to the research community of patentable 
research resources (e.g., transgenic and mutant animals, mutagenesis 
protocols, and genetic and phenotypic data for all mutant strains) developed 
during this project;
o Program priorities and program balance;
o Availability of funds.

INQUIRIES

Inquiries concerning this RFA are encouraged.  The opportunity to clarify any 
issues or answer questions from potential applicants is welcome.  

The letter of intent should be sent 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
E-mail:  KleinS@Exchange.nih.gov  

A complete listing of contacts for both programmatic and fiscal/administrative 
inquiries may be found at http://www.nichd.nih.gov/rfa/HD-01-008/hd-01-008.htm

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.865 (NICHD); 93.862 (NIGMS); 93.113 and 93.114 (NIEHS); 93.242 (NIMH), and 
93.853 (NINDS).  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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	Office of Extramural Research (OER)			National Institutes of Health (NIH) 9000 Rockville Pike Bethesda, Maryland 20892			Department of Health and Human Services (HHS)
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