and Human Services (HHS)
EXPIRED
This Program Announcement expires on March 1, 2004, unless reissued.
DEVELOPMENT OF ZEBRAFISH MUTAGENESIS AND SCREENING TOOLS
Release Date: March 19, 2001
PA NUMBER: PA-01-070
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.
PURPOSE
This Program Announcement (PA) is to encourage investigator-initiated
applications for research designed to exploit the power of mutagenesis
screening in zebrafish in order to detect and characterize genes, pathways,
and phenotypes of interest in development and aging, organ formation,
behavior, and disease processes. Applications that propose to advance the
technologies associated with such phenotyping also are welcome. This PA is a
continuation of the program initiated by RFA HD-00-004, Mutagenesis
Screens/Phenotyping Tools for Zebrafish
(http://grants.nih.gov/grants/guide/rfa-files/RFA-HD-00-004.html). 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 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. Applications from new investigators are
particularly encouraged. Racial/ethnic minority individuals, women, and
persons with disabilities are encouraged to apply as Principal Investigators.
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 any 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, and the mutants and
tools developed 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 most recent RFA, this PA is being released to provide
an umbrella under which to continue NIH efforts to support mutagenesis
screening and development of phenotyping tools for zebrafish.
In the past decade, mutational analyses in the non-vertebrate genetic models
of the worm (Caenorhabditis elegans) and the fruitfly (Drosophila
melanogaster) have contributed significantly to our understanding of early
developmental pathways. For example, these studies have led to the discovery
of genes encoding signals, components of signaling systems, enzymes, and
transcriptional regulators that act during embryonic development. These genes
often operate in complex cascades to regulate pattern formation, cell fate,
and specification, as well as later events such as development of the eye,
heart, and other organs. While these invertebrate systems have revealed much
information and shown that numerous aspects of development are highly
conserved among invertebrates and vertebrates, many features of patterning and
morphogenesis of the vertebrate embryo are distinct and thus cannot be studied
in invertebrates. The vertebrate embryo has many characteristics not found in
invertebrates, including a substantially different body plan and greater
complexity of the nervous system, as well the presence of organs that have no
clear counterparts in simple invertebrates. Thus, a complete understanding of
human development will require experimentation in vertebrate model organisms.
The study of mutations that affect development has been possible in the mouse,
but the mouse embryo is not accessible in utero throughout much of its
development. Consequently, mutational studies in this species have been
limited largely to defects in postnatal maturation. While reverse genetics
(e.g., gene knockouts) have been useful in the mouse model, the substantial
cost of maintaining large mouse colonies has limited the applicability of
forward genetic approaches on a large scale. These limitations will have a
profound impact on the rapid discovery of genes important in vertebrate
development, and relevant to human disease.
As a vertebrate, the zebrafish, Danio rerio, is more closely related to humans
than are yeast, worms or flies. It has a number of advantageous features as a
model organism for study of vertebrate development, disease, and biological
pathways. 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 easily
obtainable in large numbers and accessible throughout development, they are
transparent, and they undergo rapid organogenesis, making them very amenable
for developing phenotypic screens. 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 a developmental, environmental or genetic perturbation. The use of
zebrafish to study vertebrate development, disease, and pathways of interest
has been validated further by the demonstration that many of its genes show a
high degree of structural and functional similarity to their human homologues.
The most powerful and unique feature of the zebrafish is that it is a
vertebrate model organism with a proven track record of easily executed,
large-scale forward mutagenesis screens.
As reported in the December 1996 issue of Development, 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 that
are important to auditory and vestibular function. While this large-scale
screen focused primarily on developmental defects, it is clear that saturation
mutagenesis of the zebrafish genome will be an indispensable means of
achieving a complete understanding not only of development, but also of the
physiology, behavior, aging, and disease processes of this vertebrate. RFA-
HD-00-004 has boosted efforts for zebrafish mutagenesis screening, including
screening of adult fish, and the current initiative is intended to further
this effort.
Research Scope
The objective of this PA is to continue to broaden the range, power, and
utility of screens for new mutants of zebrafish. It will, therefore, support
proposals for development of improved or novel methods for mutagenesis
screens, as well as proposals for the actual execution of such screens.
Methodology developed and data and mutants generated as a result of this PA
are expected to be made widely available to the research community.
Applicants must include as part of their applications a plan for disseminating
these resources, adequacy of this plan will be considered in making funding
decisions for applications responding to this PA (see AWARD CRITERIA, below).
Objectives to be addressed in applications submitted in response to this PA
include, but are not limited to, the following:
o Development and/or application of novel phenotypic screens for mutants.
These screens may be based on observation of alterations in morphology,
physiology or behavior.
o Development and/or application of novel methods of mutagenesis (e.g.,
insertional).
o Genetic screens focusing on identifying mutations that affect the structure
and function of specific tissue/organ systems.
o Screens focusing on identifying novel developmental genes and pathways,
including those mediating sensitivity or resistance to environmental
teratogens.
o Screens to analyze the genetic basis of adult phenotypes including behavior,
aging, organ disease, cancer, and responses to environmental toxins, alcohol,
and drugs.
o Screens to detect altered gene expression patterns, as a tool to identify
components of genetic pathways or those altered by environmental agents.
o Sensitized screens, using strains carrying a known mutation, in order to
identify extragenic suppressors or enhancers of that mutation.
In addition, all applications are expected to address the following:
o A proposed sharing plan to insure that mutant zebrafish, sperm, embryos,
genetic and phenotypic screens, mutagenesis protocols, and genetic and
phenotypic data for all mutant strains are widely available to the scientific
community.
o A proposed plan addressing if, or how, the Principal Investigator and
grantee institution will exercise their intellectual property rights regarding
patentable research resources, such as mutant fish, sperm, embryos, genetic
and phenotypic screens, mutagenesis protocols, and genetic and phenotypic data
for all mutant strains produced in projects funded under this PA (see SPECIAL
REQUIREMENTS, below).
Interests of Participating Institutes and Centers
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.
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.
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.
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.
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, and studies to define the molecular
mechanisms that dictate cell-specific gene expression in relevant cell types.
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.
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, normal function, and diseases of the
nervous system. This research might include the use of mutants to understand
the mechanisms controlling the following processes: neurogenesis, nervous
system patterning, cell lineage, cell migration, programmed cell death, axon
pathfinding and regeneration, myelination, and motor and sensory function.
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.
SPECIAL REQUIREMENTS
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 as well as other research areas such as
developmental biology. 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_2001/index.htm), Principles and
Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining
and Disseminating Biomedical Research Resources: Final Notice, December 1999
(http://www.ott.nih.gov/policy/rt_guide_final.html) and
(http://ott.od.nih.gov/pdfs/64FR72090.pdf)]. Biomaterials (e.g.,
pathogen-free mutant animals, preserved sperm and embryos, etc.) and other
patentable research resources (e.g., genetic and phenotypic screens,
mutagenesis protocols, and genetic and phenotypic data for all mutant strains,
etc.) developed in projects funded as a result of this PA 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 PA become readily available to the research community in a timely
manner for further research, development, and application, in the expectation
that this will lead to products and knowledge of benefit to the public health.
Accordingly, for applications submitted in response to this PA, there are two
special requirements regarding research resources produced in the proposed
project:
(1) Applicants are required to include in their applications a specific plan
by which they will share research resources with the wider scientific
community.
(2) Applicants are required to 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., mutant fish,
embryos and sperm, genetic and phenotypic screens, mutagenesis protocols, and
genetic and phenotypic data for all mutant strains, etc.).
Each of the two requirements are discussed in detail below.
Both the sharing and intellectual property plans should, at a minimum, address
the elements discussed in detail below in a clear and concise manner.
Applicants are encouraged to inform and/or confer with their institutional
offices of technology transfer to develop plans for addressing these
requirements.
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 PA to propose detailed plans for sharing the research
resources generated through the grant. It is expected that the resources to
be shared include, for example, all materials developed in projects funded
under the PA, including but not limited to, the following: mutant fish,
embryos and sperm, genetic and phenotypic screens, mutagenesis protocols, and
genetic and phenotypic data for all mutant strains.
The National Resource for Zebrafish at the University of Oregon is being
established as a focal point for sharing of resources among investigators
using zebrafish. Currently, the Resource is capable of accepting frozen sperm
and some live fish stocks. It is expected to be fully operational, with
expanded capacity to accept live fish stocks, by Spring 2001. In addition to
serving as a stock center, the Resource operates a comprehensive database, the
Zebrafish Information Network (ZFIN). Plans to share materials generated by
projects under this PA through the National Resource for Zebrafish should
include evidence/documentation of coordination with investigators at the
Resource. Plans to deposit fish at the Resource should state whether this
will be done as frozen sperm or live fish stocks. For frozen sperm, adequate
personnel and funding must be requested to produce, cryopreserve, and ship the
sperm according to Resource specifications and using appropriate shipping
containers available from the Resource. For live fish stocks, it must be
clear that the Resource is prepared to accept the numbers of stocks to be
generated or agrees to handle the demands of producing and freezing sperm from
live stocks deposited. Plans to deposit reagents should likewise be
coordinated. Plans for informatics should be coordinated with the Resource to
ensure that necessary hardware/software requirements can be accommodated for
automatic deposit of data finalized by individual laboratories to ZFIN on a
periodic basis. A reasonable time frame for periodic deposition of mutants,
sperm, reagents, and data should be specified in the application and will be
considered during the review of the plan for sharing.
The adequacy of the plan will be considered by NIH program staff on the TZCC
and will be important in determining whether the grant shall be awarded. The
sharing plan, as approved, 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 PA become readily available to the research community. With regard to
patentable research results, for example, mutants identified through genetic
and phenotypic screens, embryos, oocytes and sperm for these mutants, genetic
and phenotypic screens, mutagenesis protocols, and genetic and phenotypic data
for all mutant strains and methodologies, the NIH requires applicants who
respond to this PA to develop and propose a plan addressing how they will make
available to the broader scientific community research resources produced in
projects funded under this PA.
The requirement for this intellectual property rights plan is in addition to
the requirement for the research resources sharing plan described above. The
adequacy of the proposed plan will be considered by NIH program staff on the
TZCC in determining whether the grant shall be awarded. The plan, as approved,
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 Institute reserves the right to monitor awardee
activity in this area to ascertain if patents or patent applications on
technology arising out of this funded research (e.g., 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) are adversely affecting the goals of
this PA and the overall mission of benefiting the public health.
Points to Consider When Proposing the Sharing and Intellectual Property Plans
Applicants should consider the following points when developing their
proposals for sharing and intellectual property plans:
o Do the plans fully adhere to the NIH Grants Policy on Sharing of Unique
Research Resources including the Sharing of Biomedical Research Resources
Principles and Guidelines for Recipient of NIH Grants and Contracts
(http://www.ott.nih.gov/policy/rt_guide_final.html)?
o Will material transfers be made with no more restrictive terms than in the
Simple Letter MTA or the UBMTA and without reach through requirements?
o Should any intellectual property arise which requires a patent, will the
technology (e.g., materials, data, etc.) remain widely available to the
research community?
Post-Award Management
During the course of the award period, the Principal Investigators may be
invited 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. Overall application budget requests should include
travel funds for the Principal Investigator to attend biennial meetings in the
metropolitan Washington, D.C. area scheduled to alternate with the Zebrafish
Development and Genetics Meetings.
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
301-710-0267, E-mail: [email protected].
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 and will be reviewed for completeness by the Center for Scientific
Review. 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 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 Adequacy of plans to make widely available to the research community in a
timely manner 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 (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
and methodologies) developed during this project,
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_Mutagenesis.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, 93.855,
93.846, 93.173, 93.837, 93.849, 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.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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