This Program Announcement expires on May 15, 2004, unless reissued.

THE ZEBRAFISH AS AN ANIMAL MODEL FOR DEVELOPMENT AND DISEASE RESEARCH

Release Date:  May 16, 2001

PA NUMBER:  PA-01-095

Trans-NIH Zebrafish Coordinating Committee
 (http://www.nih.gov/science/models/zebrafish/)
National Institute of Child Health and Human Development
 (NICHD; http://www.nichd.nih.gov/)
National Cancer Institute
 (NCI; http://www.nci.nih.gov/)
National Center for Research Resources
 (NCRR; http://www.ncrr.nih.gov/)
National Eye Institute
 (NEI; http://www.nei.nih.gov/)
National Human Genome Research Institute
 (NHGRI; http://www.nhgri.nih.gov/)
National Institute on Aging
 (NIA; http://www.nih.gov/nia/)
National Institute on Alcohol Abuse and Alcoholism
 (NIAAA; http://www.niaaa.nih.gov/)
National Institute of Arthritis and Musculoskeletal and Skin Diseases
 (NIAMS; http://www.nih.gov/niams/)
National Institute on Deafness and Other Communication Disorders
 (NIDCD; http://www.nidcd.nih.gov/)
National Institute of Dental and Craniofacial Research
 (NIDCR; http://www.nidr.nih.gov/)
National Institute of Diabetes and Digestive and Kidney Diseases
 (NIDDK; http://www.niddk.nih.gov/)
National Institute on Drug Abuse
 (NIDA; http://www.nida.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/)
National Institute of Neurological Disorders and Stroke
 (NINDS; http://www.ninds.nih.gov/)

THIS PA 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 PA.

This Program Announcement replaces PA-98-074.

PURPOSE

The purpose of this Program Announcement (PA) is to solicit applications as 
part of a National Institutes of Health (NIH) initiative to increase our 
support of the zebrafish as an animal model for development, organ formation, 
behavior, aging, and disease research.  This PA is a reissuance of PA-98-074, 
which was published in the NIH Guide for Grants and Contracts, Vol. 5, No. 22 
on May 21, 1998.  This effort stems from an NIH initiative with participation 
of the Institutes and Centers listed above, working though the Trans-NIH 
Zebrafish Coordinating Committee (TZCC; 
http://www.nih.gov/science/models/zebrafish/) under the co-chairmanship of 
NICHD and NIDDK.  Since its formation in 1997, the committee has played an 
active role as an advocate for the zebrafish as an important model for 
development, organ formation, behavior, aging, and disease research. 

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 PA is related to one 
or more of the 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.  Applications from new investigators are particularly 
encouraged.

MECHANISM OF SUPPORT

This PA will use the National Institutes of Health (NIH) individual research 
project grant (R01) award mechanism.  Because the nature and scope of the 
research proposed in response to this PA may vary, it is anticipated that the 
size of awards will also vary.  Responsibility for the planning, direction, 
and execution of the proposed project will be solely that of the applicant.

Although this PA is the result of a trans-NIH initiative, awards will be made 
through the Institute or Center whose mission is most closely related to the 
proposed work.  Through TZCC, each funding component will share with the 
other committee members findings of research supported as a result of this 
PA.  All investigators funded under this initiative will be expected to work 
together cooperatively so that the information learned will be of maximum 
usefulness to the community.

For all competing applications requesting up to $250,000 direct costs per 
year, specific application instructions have been modified to reflect 
"MODULAR GRANT" and "JUST-IN-TIME" streamlining efforts being examined by 
NIH.  Complete and detailed instructions and information on Modular Grant 
applications can be found at 
http://grants.nih.gov/grants/funding/modular/modular.htm.  Applications that 
request more than $250,000 in any year must use the standard PHS 398 (rev. 
4/98) application instructions.

RESEARCH OBJECTIVES

Background

The TZCC continues to play an active role as an advocate for the zebrafish 
model.  The committee’s initial efforts resulted in RFA DK-98-006, entitled 
“Genomic Resources for the Zebrafish,” and continued with a Program 
Announcement, PA-98-074, entitled ”The Zebrafish as an Animal Model for 
Development and Disease Research.”  On May 10-11, 1999, the TZCC sponsored a 
workshop entitled “Genomic and Genetic Tools for the Zebrafish.”  At this 
workshop, which expanded upon the “Non-mammalian Models Workshop” held on 
February 16-17, 1999, zebrafish researchers were asked to help prioritize the 
short- and long-term needs of the community.  One result of the workshop was 
the recommendation that more genetic screens in the zebrafish need to be 
supported by the NIH.  RFA-HD-00-004, entitled “Mutagenesis 
Screens/Phenotyping Tools for Zebrafish,” addressed, in part, this and some 
of the other recommendations made by workshop participants.  Due to the 
response of the community to this RFA, a follow-up PA (PA-01-070; 
http://grants.nih.gov/grants/guide/pa-files/PA-01-070.html) was recently 
released to provide an umbrella under which to continue NIH efforts to 
support mutagenesis screening and development of phenotyping tools for 
zebrafish.  Since there has a been a continued interest in the further 
development of this animal model, the original Program Announcement, PA-98-
074, ”The Zebrafish as an Animal Model for Development and Disease Research,” 
is being reissued here under the same title.

Vertebrate development has been characterized extensively using the methods of 
classical embryology, molecular biology, and biochemistry.  However, mutational 
analysis in vertebrates has lagged behind such investigations in invertebrates.  
As experimentation in Drosophila melanogaster and Caenorhabditis elegans has 
established, mutational studies are a powerful tool to determine the events that 
result in patterning and morphogenesis of the embryo.  When combined with genetic 
combinatorial analyses, mutational analyses can identify specific genes that act 
during embryonic development, provide insight into how they function, and clarify 
the pathways in which they participate.  Studies that compare results from these 
invertebrate systems with those obtained in vertebrates have established that 
there is remarkable evolutionary conservation in the genetic programs that 
determine embryo formation, including such early patterning events as formation of 
the embryonic axes, but also including later events such as development of eye, 
heart, and other organs.  Although invertebrate systems are extremely powerful and 
numerous aspects of development are conserved, many aspects of patterning and 
morphogenesis of the vertebrate embryo are distinct and cannot be studied in 
invertebrates.  The vertebrate embryo has many features not present in other 
models, including the substantially different organization and greater complexity 
of the nervous system, and the fact that some vertebrate organs have no clear 
cognates in the simpler invertebrates.  Thus, understanding human development will 
require application of experimental approaches to the formation of the vertebrate 
embryo.  Some assessment of mutations that affect development has been possible in 
the mouse, but the mouse embryo is inaccessible in utero throughout much of its 
development.  Consequently, mutational studies in this species have been limited 
largely to defects in post-natal maturation.  While reverse genetics (e.g., knock-
outs) have been useful in the mouse model, the substantial costs of maintaining 
large mouse colonies have limited the applicability of forward genetic approaches, 
which will have a profound impact on our understanding of development.

As a vertebrate, the zebrafish, Danio rerio, is more closely related to humans 
than are yeast, worms or flies.  It has a number of valuable features as a model 
organism for study of vertebrate development.  Many features of zebrafish 
development have been characterized, including early embryonic patterning, early 
development of the nervous system, and aspects of cell fate and lineage 
determination.  The embryos are transparent and accessible throughout development.  
In live embryos, the same specific cell or even cellular processes can, in many 
cases, be identified from individual to individual, affording a high level of 
precision in characterizing the effect of developmental or genetic perturbation.  
Techniques for ablation and transplantation of individual cells have been used to 
explore questions about induction and cell fate, and continue to be refined.  
There are also a growing number of molecular markers to facilitate developmental 
studies.  Because of their relatively short reproductive cycle, the large number 
of progeny that can be produced, and the relatively small space needed to maintain 
large numbers of offspring, the zebrafish is an efficient vertebrate model system 
for genetic analysis.  It is possible to generate haploid progeny, which are 
viable to the point where many recessive embryonic phenotypes can be identified, 
and also homozygous diploid progeny that carry only maternal (or paternal) genetic 
information.  A genetic map of approximately two - three centimorgan resolution is 
available, and mutations can be readily placed on the map.  Positional cloning of 
genes identified by mutation has recently been accomplished.  Finally, there are 
several promising methods for transformation and insertional mutagenesis which are 
now being developed.

A number of mutagenesis screens have been performed to date and the transparent 
embryos examined for defects in overall embryonic pattern, morphogenesis or organ 
formation.  These screens have identified a substantial number of mutations that 
affect the formation of organ systems, including defects in the nervous system, 
skeletal muscle, craniofacial region, kidney and endocrine organs, cardiovascular 
and gastrointestinal systems, and the sensory cells of lateral line systems, which 
are important to auditory and vestibular function.  For most of these mutations, 
the gene defect has not yet been identified.  It is likely that many of these 
mutations affect genes relevant to human development and aging and disease 
processes such as neurodegeneration and cancer.  The zebrafish offers the 
opportunity of using classical genetics to define gene functions.

Scope

The NIH is interested in helping to develop and support tools to improve the 
ability of model organisms to elucidate the genetic and molecular mechanisms that 
regulate normal and abnormal biological processes.  The zebrafish is one such 
model that holds tremendous promise to increase our understanding of vertebrate 
biology.  The principle objective of this PA is to continue to promote the 
zebrafish as an animal model for the study of development, organ formation, 
behavior, aging, and disease research.  Applications for investigator-initiated 
research projects that will use state-of-the-art methods, and that will develop 
any necessary new technologies to address well-defined hypothesis-driven research 
questions will be appropriate for this PA.   The goals of this PA are to encourage 
new and innovative research and approaches using the zebrafish to identify the 
genes and elucidate the molecular and genetic mechanisms responsible for normal 
and defective development, organ formation, behavior, aging, and disease.

Each of the participating Institutes and Centers has specific interests in using 
the zebrafish as a model system to better understand particular processes, organs 
or diseases.  In addition, some may be interested in supporting development of 
methods, either general techniques or techniques that may particularly apply to 
their areas of interest.  The participating NIH Institutes and Centers have 
provided a brief outline of their interests as they relate to the goals of this 
PA.  These brief mission statements are intended to give some understanding of the 
breadth of the biomedical areas of interest in development of this model and are 
listed below in alphabetical order.  Participating Institutes have included 
examples of research topics that are appropriate for this PA; however, they are 
not to be considered as exclusive or limiting.

Institute and Center Statements of Interest

NCI:  Generation and study of zebrafish models to identify and place genes in 
functional pathways that affect growth and development; in particular, 
genes/pathways that, when altered, result in uncontrolled or cancerous 
growth.  Identification of key sites within these pathways that could be 
exploited for cancer therapeutic discovery purposes. 

NCRR:  The NCRR supports research projects that broaden the utility of the 
zebrafish model for cross-cutting biomedical research that is not encompassed 
within a single NIH Institute or Center.  Interests include, but are not 
limited to, development of new methods for mutagenesis and/or phenotypic 
characterization that would be of use in research on a wide range of diseases 
or organs, particularly if these methods could be applied to other animal 
models as well as the zebrafish. 

NEI:  Fundamental mechanisms underlying all aspects of eye development, 
function, and disease, including development of the retina and lens, optic 
nerve axon guidance, and the neural circuitry producing eye movements and 
oculomotor behaviors. 

NHGRI:  Proposals for the development of high throughput, widely applicable 
technologies or methodologies to examine gene function on a genomic scale.  
This could include initial development of high throughput or large-scale 
methods for examining gene expression, development of tools for comprehensive 
mutational analysis, or genome-scale identification of regulatory regions. 

NIA:  Basic research on the genetic and molecular basis of aging and 
longevity.  Generation and analysis of late-age onset or long-lived mutants 
that can be used to identify, clone, and characterize genes involved in 
normal and pathological aging.  Cellular and molecular function of genes 
expressed, for example, in the aging nervous system, cardiovascular, immune, 
and musculoskeletal systems.  Such genes include, but are not limited to, 
those involved in neurodegenerative disorders, neuroplasticity, cell death, 
damage and repair of DNA and proteins, and oxidative metabolism, and 
maintenance of differentiated cell function. 

NIAAA:  Mechanistic studies of ethanol-induced teratogenesis, behavioral 
impairments, and organ damage. 

NIAMS:  Mutations that have the potential to illuminate the development and 
function of the vertebrate musculoskeletal system and skin. The 
musculoskeletal system includes muscle, bone, articulated joints, cartilage, 
tendon, and ligament.  Priority will be given to the establishment of 
collaborations between investigators with expertise in the zebrafish and 
investigators with expertise in the musculoskeletal systems and skin of 
mammals and humans. 

NICHD:  Identification, cloning, and characterization of the genes important 
in normal development as well as those mutant genes that cause developmental 
defects. Elucidation of the cellular, biochemical, molecular, and genetic 
mechanisms underlying normal and defective development.  This includes, but 
is not limited to, the study of general mechanisms of pattern formation and 
cell lineage, neural crest development, cell specification, differentiation, 
migration, and fate in early development of many organs/systems such as limb, 
nervous system, immune system, and heart. 

NIDA:  Identification of mechanisms underlying tolerance, sensitization, and 
addiction to drugs of abuse such as nicotine, amphetamine, cocaine, opiates, 
barbiturates, and hallucinogens. Identification of genetic suppressors and 
enhancers of the teratological effects of drugs of abuse on behavior and the 
nervous system.  Processes involved in the development of brain regions 
mediating the hedonic properties of drugs of abuse. 

NIDCD:  Identification and cloning of genes involved in the normal and 
disordered development of hearing, balance, smell, and taste sensory systems. 
Elucidation of the cellular, molecular, and biochemical mechanisms governing 
the proliferative, plastic, and regenerative capacities of these sensory 
cells and tissues. 

NIDDK:  Research on diabetes, particularly studies on pancreatic beta cell 
function and development, obesity and mechanisms underlying satiety, other 
endocrine and metabolic diseases, hematologic disorders, and diseases of the 
digestive system, liver, kidney, and urinary tract.  Studies aiming to 
clarify the cellular and molecular events that dictate tissue and organ 
formation in all these systems are considered of relevance.  These studies 
could include, but need not be limited to, studies to develop cell lines from 
any of the tissues or organs of interest, studies to characterize normal or 
abnormal function of tissues or organs of interest, methods to screen and 
identify additional mutations in these systems, studies to define the 
molecular mechanisms that dictate cell-specific gene expression in relevant 
cell types. 

NIDCR:  All aspects of normal and abnormal craniofacial development, 
including genetics, complex origins of craniofacial disorders, cell lineages 
and differentiation, cell signaling and gene regulation, embryonic 
patterning, imaging, biomimetics, and new technologies for high-throughput 
genetic and protein screens. 

NIEHS:  Studies to examine the mechanism whereby environmental factors/agents 
alter any aspect of development. This includes the screening for mutants that 
ameliorate the toxicity of environmental agents, and the subsequent 
identification and characterization of the genes and pathways involved in 
their action. Characterization of the interactions among genetics, 
environmental agents, and time during development that lead to structural or 
functional abnormalities.  Studies to examine the mechanistic pathways 
involved in developmental exposure to environmental agents and subsequent 
increased susceptibility to adult onset disease (developmental imprinting).  
Development of a mechanistically based model for testing environmental agents 
for developmental toxicity.

NIGMS:  Basic biomedical research that addresses fundamental biological 
mechanisms such as those that underlie gene regulation, chromosome 
organization and mechanics, cell growth and differentiation, pattern 
formation, sex determination, morphogenesis, cell cycle control, behavior, 
the genetics of complex traits, and the application of mathematical models to 
complex biological systems. 

NIMH:  Investigations that examine molecular, cellular, and biochemical bases 
of genetic mutations affecting neurogenesis, biological rhythms, learning, 
memory, and other cognitive functions and behaviors of the nervous system. 
These studies include, but are not limited to, development of screening 
methods for such mutations, identification, isolation, mapping, and 
functional analyses of the genes underlying mutations. 

NINDS:  Research on the development and function of the nervous system. 
Possible projects include, but are not limited to, studies of neurogenesis, 
nervous system patterning, cell lineage, cell migration, programmed cell 
death, axon pathfinding and regeneration, myelination, and cognitive, motor 
and sensory function.  Analyses of mutants that may serve as models for 
neurological disorders are also encouraged.

The areas of interest listed above are not presented in any order of 
priority; they are only examples of areas of research to consider.  
Applications representing areas of interest to more than one Institute or 
Center will be assigned to multiple Institutes or Centers for funding 
consideration.  Applicants are encouraged to propose work in other areas that 
are related to the objectives and scope of this PA.

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 view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.

APPLICATION PROCEDURES

Applications are to be submitted on the grant application form PHS 398 (revised 
4/98) and will be accepted at the standard application deadlines as indicated in 
the application kit.  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.   

Applicants planning to submit an investigator-initiated new (type 1), competing 
continuation (type 2), competing supplement, or any amended/revised version of the 
preceding grant application types requesting $500,000 or more in direct costs for 
any year are advised that they must contact the Institute program staff before 
submitting the application, i.e., as plans for the study are being developed.  
Furthermore, applicants must obtain agreement from program staff that the 
Institute will accept the application for consideration for award.  Finally, 
applicants must identify, in a cover letter sent with the application, the program 
staff member and Institute who agreed to accept assignment of the application.  

This policy requires an applicant to obtain agreement for acceptance of both any 
such application and any such subsequent amendment.  Additional information about 
this policy may be found in the NIH Guide for Grants and Contracts, March 20, 1998 
at:  
http://grants.nih.gov/grants/guide/notice-files/not98-030.html.   

SPECIFIC INSTRUCTIONS FOR MODULAR GRANT APPLICATIONS

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. 

Modular Grant applications will request direct costs in $25,000 modules, up 
to a total direct cost request of $250,000 per year.  (Applications that 
request more than $250,000 direct costs in any year must follow the 
traditional PHS398 application instructions.) 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. 

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 each year.  This is not a Form Page. 

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) for each year, each 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. 

Provide an additional narrative budget justification for any variation in the 
number of modules requested. 

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 initial budget period and all 
future budget years. 

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 title and number of the program announcement 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)

REVIEW CONSIDERATIONS

Applications will be assigned on the basis of established PHS referral guidelines. 
Upon receipt, applications will be reviewed for completeness by the Center for 
Scientific Review (CSR).  Incomplete applications will be returned to the 
applicant without further consideration.  Applications will be evaluated for 
scientific and technical merit by an appropriate scientific review group convened 
in accordance with the standard NIH peer review procedures.  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 applications under review, will be discussed, 
assigned a priority score, and receive a second level review by the appropriate 
national advisory council or board.

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:  Does this study address an important problem?  If the aims 
of the application are achieved, how will scientific knowledge be advanced?  
What will be the effect of these studies on the concepts or methods that 
drive this field?

(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 accordance with NIH policy, all applications also will 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 of human, animals, or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application. 

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 program to accomplish the goals of this PA and address 
the needs of the participating Institutes and Centers as regards their interest in 
the zebrafish as a model organism;

o Program priorities and program balance; 

o Availability of funds. 

INQUIRIES

Potential applicants are strongly encouraged to contact program staff with 
any questions regarding the responsiveness of their proposed project to the 
goals of this PA. 

Written and telephone inquiries concerning this PA are encouraged. The 
opportunity to clarify any issues or questions from potential applicants is 
welcome.  A complete listing of contacts for both programmatic and 
fiscal/administrative inquiries may be found at:  
http://www.nichd.nih.gov/PA/Zebrafish_animalModel.htm. 

AUTHORITY AND REGULATIONS 

This program is described in the Catalog of Federal Domestic Assistance Nos. 
93.865, 93.396, 93.306, 93.867, 93.839, 93.172, 93.866, 93.273, 93.846, 
93.173, 93.121, 93.847, 93.848, 93.849, 93.279, 93.113, 93.862, 93.242, 
93.853.  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 and contract 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, and 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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