MOUSE PHENOTYPING: DEVELOPMENTAL AND FERTILITY DEFECTS Release Date: October 9, 2001 RFA: RFA-HD-01-020 National Institute of Child Health and Human Development (http://www.nichd.nih.gov) Letter of Intent Receipt Date: February 11, 2002 Application Receipt Date: March 13, 2002 PURPOSE This Request for Applications (RFA) solicits applications to phenotype mutant mouse strains with developmental and fertility defects and to characterize the mutations responsible for their defects. These projects should be designed to characterize mouse strains with defects in development and reproduction so as to isolate new alleles of known genes and identify new genes that are involved in the processes of development and fertility. The mouse strains to be characterized should be obtained from existing mouse mutagenesis projects. Appropriate sources of mutant strains include both small-scale mutagenesis projects and large-scale mutagenesis facilities, such as the NIH-funded mouse mutagenesis and phenotyping facilities at Baylor College of Medicine, Northwestern University, Jackson Laboratory, and the University of Tennessee. Characterizing these mouse strains, and their mutations, is expected to help elucidate the basic cellular, molecular, and genetic mechanisms that direct embryonic and post-embryonic development, as well as yield insights into the mechanisms that control fertility. These projects should identify and obtain mutant mouse strains with disrupted development and fertility, phenotype the strains to provide a detailed characterization of the defects, and characterize the mutations and the genes responsible for the defects. The phenotypic characterization may also include high-throughput screens to identify a broad range of general features of these strains, where appropriate. The detailed characterization should describe the specific cellular, molecular, and genetic features of the defects, whereas high-throughput screens, if included, should provide a general overview of the biological features of the animals with these defects. Characterization of the mutations and genes should include analyses to increase the value of the mutants to the scientific community, such as genetic mapping to localize the mutations within the genome. These projects will be part of NIH’s initiative to determine the function of mammalian genes. Accordingly, their activities will be coordinated with related facilities, including the NIH-funded Mouse Mutagenesis and Phenotyping: Developmental Defects Facility at Baylor College of Medicine (http://www.mouse-genome.bcm.tmc.edu/ENU/MutagenesisProj.asp). Additionally, the mutant strains, phenotypic and genetic information, protocols, assays, assessment criteria, and other materials and information generated by projects funded under this RFA will be made available to the wider biomedical community. Further information about NIH initiatives on mouse genomics and genetics resources is available at http://www.nih.gov/science/mouse. HEALTHY PEOPLE 2010 The Public Health Service (PHS) is committed to achieving the health promotion and disease prevention objectives of "Healthy People 2010," a PHS- led national activity for setting priority areas. This RFA is related to one or more priority areas. Potential applicants may obtain "Healthy People 2010" at http://www.health.gov/healthypeople/. ELIGIBILITY REQUIREMENTS Applications may be submitted by domestic, for-profit and non-profit organizations, public and private, such as universities, colleges, hospitals, and laboratories, units of State and local governments, and eligible agencies of the Federal government. Applications will not be accepted from foreign institutions. Racial/ethnic minority individuals, women, and persons with disabilities are encouraged to apply as Principal Investigators (PIs). MECHANISM OF SUPPORT This RFA will use the National Institutes of Health (NIH) Cooperative Research Project Grant (U01) award mechanism, an assistance mechanism (rather than an acquisition mechanism) in which substantial NIH scientific and/or programmatic involvement with the awardee is anticipated during performance of the activity. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients activity by involvement in the activity and otherwise working jointly with the award recipients in a partner role, but it is not to assume direction, prime responsibility, or a dominant role in the activity. Details of the responsibilities, relationships, and governance of the studies to be funded under cooperative agreements are discussed below under Terms and Conditions of Award. This RFA is a one-time solicitation. The earliest anticipated award date is September 30, 2002. FUNDS AVAILABLE The NICHD intends to commit approximately $3 million in total costs [direct plus Facilities and Administrative (F&A) costs] in FY 2002 to fund about four new grants in response to this RFA. An applicant may request a project period of up to five years. Because the nature and scope of the research proposed may vary, it is anticipated that the size of each award also will vary, with an average total cost of approximately $750,000 per year. However, in no case should total costs requested exceed $1.5 million per year. Although the financial plans of the NICHD provide support for this program, awards pursuant to this RFA are contingent upon the availability of funds and the receipt of a sufficient number of meritorious applications. RESEARCH OBJECTIVES Background In 1998, the NIH convened a large group of distinguished scientists to recommend priorities for generating mouse genetic and genomic resources to help elucidate the genetic basis of human health and disease. The recommendations included functional analyses of the mouse genome (see http://www.nih.gov/welcome/director/reports/mgenome.htm). In response to this recommendation, 13 of the NIH institutes issued a pair of RFAs to support facilities to perform genome-wide mutagenesis and large-scale phenotyping of the resulting mutants. Those RFAs led to the establishment of four mutagenesis and phenotyping facilities in 2000 and early 2001. One is focused on developmental defects (Baylor College of Medicine) and three are focused on the nervous system and behavior (Northwestern University, University of Tennessee, and Jackson Laboratory). Several other similar facilities are currently in operation and others will begin soon. These facilities are producing a large number of mutant mouse strains that are providing new and critical insights into the mechanisms that govern normal and disrupted biological processes. The projects to be funded by the current RFA will aid in characterizing the strains that display defects in development and in fertility regulation, and in identifying the mutations and the genes that control these processes. Scope and Objectives This RFA will support projects to phenotype mouse strains of utility for understanding embryonic development, post-embryonic development, and reproduction, and to characterize the mutations and the genes involved in these processes. The scope of the proposed research may range from small projects that focus on the specific details of a few phenotypes to larger projects that examine many phenotypes and that characterize a broad range of features of those phenotypes. Funded projects will make available obtained phenotypic and genetic data for wide distribution. Additionally, they will make available mutant strains that are generated by the projects. In particular, these projects will be required to: o Identify and obtain mutant mouse strains that are appropriate for studying embryonic and post-embryonic development and fertility regulation. Include strains with mutations that are recessive and dominant, and viable and embryonic lethal, as appropriate. These strains may be obtained from any appropriate source, including small-scale mutagenesis projects and large- scale mutagenesis facilities, such as the four NIH-funded mouse mutagenesis and phenotyping facilities mentioned above. Describe the source(s) of the mutant mouse strains to be used, justify their appropriateness for the proposed studies, and provide evidence of their availability. o Perform phenotypic analyses to identify and characterize developmental and/or fertility defects (see examples, below). The goal of the characterization should be to elucidate the defect’s biological and genetic features. The scope of projects may range from those designed to identify and examine a few categories of defects to those designed to identify and examine many categories of defects. Additionally, projects may include high- throughput phenotypic screens to identify and summarize a broad range of features of the mutant strains with developmental and/or fertility defects. If included, these screens should be designed to identify and characterize the developmental, reproductive, anatomical, cellular, physiological, molecular, genetic, metabolic, and/or pathological features of the mutants with the defects. o Characterize the mutations by performing analyses that will make the mutants maximally useful to the scientific community. Analyses should include rapid genetic mapping of the mutations to identify the region of the genome that contains the mutated genes, and other appropriate analyses of the mutations, genes, and gene products. o Develop and maintain a database including all of the phenotypic and mapping data on these mutant mice. o Propose a sharing plan to ensure that animals, preserved embryos/sperm, phenotyping assays, and phenotypic and genetic data for the mutant strains are widely available to the scientific community. This plan should also address if, or how, the PI and grantee institution will exercise their intellectual property rights regarding patentable research resources. These issues are addressed below under SPECIAL REQUIREMENTS. o The distribution plan must ensure that the mice, and their embryos and/or sperm, will be free from pathogens. Projects should examine mutant mouse strains with defects in development and/or fertility. Phenotypes of interest include, but are not limited to: Developmental Defects: o Defects leading to embryonic lethality, o Patterning defects, such as alterations in the basic body plan, or absence or duplication of structures, o Alterations in organogenesis, o Alterations in growth rate, Fertility Defects Resulting from Alterations in: o sex differentiation, o gametogenesis and gamete function, o development and function of the reproductive tract and gonads, o neuroendocrine control of reproduction, o neural mechanisms involved in mating behavior. Guidance and Management Structure The overall guidance and management of the program will be provided by a Steering Committee (SC). The SC is the projects main governing committee and the committee through which the NIH interacts and collaborates with the projects. It will consist of the PIs of each of the projects to be funded by this RFA, one or two NICHD Project Scientists, and a nonvoting, independent chairperson. Additional advice will be provided by the Mouse Genomics and Genetics Scientific Panel (MSP), which will help integrate and coordinate the projects funded under this RFA with other related facilities. It consists of about 10 scientists who are not affiliated with any of the projects. SPECIAL REQUIREMENTS Meetings PIs are expected to participate in two SC meetings annually, of two days duration each. Budget requests should include travel funds for the PI and critical staff to attend those meetings in the Bethesda, MD area. Milestones and Evaluations Applications should define yearly milestones, which may be modified at the time of the award. The awardee"s milestones will be provided to the SC. It is expected that the milestones should be adjusted annually at the award anniversary date, both to incorporate the group"s scientific accomplishments and progress in the field in general, as well as to reflect the recommendations of the SC and the MSP. In accordance with the procedure described under Terms and Conditions of Award, below, NICHD program staff may recommend augmenting any project, as discussed with the SC, or reducing or withholding funds if a project substantially fails to meet its milestones or to remain state-of-the-art. Research Resources Restricted availability of unique research resources, upon which further studies are dependent, can impede the advancement of research. The timely sharing of biomaterials, data, and software is an essential element of the rapid progress that has been made in the genetic analysis of mammalian genomes. Accordingly, the NIH is interested in ensuring that the research resources developed by these projects become readily available to the broader research community in a timely manner for further research, development and application, in the expectation that this will lead to products and knowledge that benefit public health. Resources to be shared will include biomaterials (pathogen-free mutant animals, preserved embryos and sperm), other patentable research resources (e.g., phenotyping assays, protocols, and instrumentation), and phenotypic and genetic data produced in projects funded by this RFA. Additionally, NIH policy requires that investigators make unique research resources readily available for research purposes to qualified individuals within the scientific community when they have been published. To address the joint interests of the government in the availability of, and access to, the results of publicly funded research, there are two special requirements regarding research resources produced in the applications submitted in response to this RFA: (1) applicants are required to include a specific plan by which they will share research resources with the wider scientific community. This plan must address if, and how, applicants will exercise their intellectual property rights while making available to the broader scientific community patentable research resources (e.g., mutant mice, phenotypic and genetic information, phenotyping assays, protocols, instrumentation, and methodologies), (2) NIH has made a Determination of Exceptional Circumstances (DEC) to eliminate the potential for patents on new mutant strains that are generated by this project and on newly identified uses of existing mutant strains. These requirements are discussed below. (1) Plan to Share Research Resources The plan to share research resources must make unique research resources readily available and accessible for research purposes to qualified individuals within the scientific community in accordance with the NIH Grants Policy Statement (see NIH Grants Policy Statement at http://grants.nih.gov/grants/policy/nihgps_2001/index.htm and Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources at http://www.ott.nih.gov/policy/rt_guide_final.html). These documents also define terms, parties, responsibilities, prescribe the order of disposition of rights, prescribe a chronology of reporting requirements, and delineate the basis for and extent of government actions to retain rights. This plan should include an elaboration of the applicant"s anticipated plans to generate, or not generate, patents and/or exclusive or non-exclusive licensing of biomaterials and other patentable subject matter created in projects funded under this RFA. This plan is also expected to include disclosure of any pre-existing intellectual property rights, including options to for-profit research sponsors, that are associated with biomaterials and data that may be generated. Standard patent rights clauses may be found at 37 CFR Part 401.14 and are accessible from the Interagency Edison web page, http://www.iedison.gov. Applicants are encouraged to discuss their plans for addressing this requirement with their institutional offices of technology transfer. It is also expected that this plan will include all elements of the guidelines developed by the NIH and the Department of Energy (DOE) to address the special needs of genome research http://www.nhgri.nih.gov/Grant_info/Funding/Statements/data_release.html. Where appropriate, the awardee may work with the private sector to make unique resources available to the wider biomedical research community at a reasonable cost. Applicants may request funds to defray the costs of sharing resources, with adequate justification. The Scientific Review Group will evaluate the adequacy of the proposed plan for sharing and data access. NICHD program staff also will consider the adequacy of the plan when determining whether a grant shall be awarded. The approved plan will become a condition of the award. Progress Reports must contain information on activities for the sharing of research resources and intellectual property, if any. Evaluation of any future renewal applications will include an assessment of the effectiveness of research resource release. (2) Determination of Exceptional Circumstances NIH is interested in ensuring that the research resources developed through this RFA become readily available to the research community in accordance with the NIH Mouse Mutagenesis and Phenotyping Initiative. To ensure unrestricted availability of mutant mice developed under this RFA, NIH has made a Determination of Exceptional Circumstances (DEC) pursuant to 37 C.F.R. 401.3(a)(2) that covers mutant animals, embryos and sperm generated by the project, and newly identified uses of existing mutant strains. The purpose of the DEC is to eliminate the potential for patents on mutant mice, embryos, sperm, and newly identified uses of existing mutant strains that could undermine the development of a widely available national resource that is the fundamental purpose of the NIH initiative to determine the function of mammalian genes. Terms and Conditions of Award The following Terms and Conditions will be incorporated into the award statement. They are to be followed in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when state and local governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies. The administrative and funding instrument used for this program will be the U01, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH scientific and/or programmatic involvement with the PI is anticipated during performance of the activities. Under the cooperative agreement, the NIH purpose is to support and/or stimulate the PI"s activities by involvement in and otherwise working jointly with the PI in a partnership role, it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the PI for the project as a whole, although specific tasks and activities may be shared between the awardee and NIH program staff. Facilities and administrative cost (indirect cost) award procedures apply to cooperative agreements in the same manner as for grants. Business management aspects of these awards will be administered by the NICHD Grants Management Branch in accordance with HHS, PHS, and NIH grant administrative requirements. 1. Awardee Rights and Responsibilities The PI will coordinate project activities scientifically and administratively at the awardee institution and at other sites that may be supported by subawards to this award. The PI will have the primary responsibility for defining the details for the project within the guidelines of this RFA, and for performing the scientific activities. The PI will agree to accept close coordination, cooperation, and participation of the NICHD Project Scientist, the Steering Committee (SC) and the Mouse Genomics and Genetics Scientific Panel (MSP) in those aspects of scientific and technical management of the project described under "Project Scientist Responsibilities," "Steering Committee Functions," and " Mouse Genomics and Genetics Scientific Panel Functions" (below). Specifically, the PI will: o Determine experimental approaches, design protocols, direct experiments, and set project milestones, in consultation with NICHD program staff and the SC, o Implement approved plans for sharing research resources, o Submit periodic progress reports in a standard format, as agreed upon by the SC, o Present results and plans at SC meetings, o Accept and implement the common guidelines and procedures approved by the SC and the MSP, o Solicit the views of the broad biomedical research community for the phenotypes and/or genotypes of interest, o Release data and publish results, as agreed upon by NICHD program staff and the SC. 2. NICHD Responsibilities NICHD Project Scientist: The NICHD Project Scientist(s) will be staff member(s) of the Developmental Biology, Genetics and Teratology Branch and/or the Reproductive Sciences Branch. They will have substantial scientific/programming involvement that includes facilitating the partnership between NIH and the phenotyping projects, helping to balance the projects activities with new and emerging research opportunities, and ensuring that the projects activities are consistent with the mission of NICHD. They will help to maintain scientific balance between accomplishing goals and addressing emerging research opportunities. The role of the NICHD Project Scientist will be to facilitate, but not to direct activities. It is anticipated that decisions will be reached by consensus with the PI through the SC. One or two Project Scientists will participate as members of the SC. NICHD staff will have a total of one vote. The NICHD Project Scientist(s) will: o Provide relevant expertise and overall knowledge, o Provide information about ongoing NIH-supported research and resource collections, o Attend SC meetings as one voting member and participate with other SC members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist(s) will assist and facilitate the group process and not direct it. They will help develop operating guidelines, quality control procedures, and consistent policies for dealing with situations that require coordinated action. The Project Scientist(s) must be informed of all major interactions of SC members, o Serve as liaison to the MSP, attend MSP meetings as a non-voting member to help coordinate the activities of the projects with those of other NIH mutagenesis and phenotyping projects, and with other NIH mouse genomics and genetics initiatives. The Project Scientist will also coordinate the activities of projects funded under this RFA with other US and international efforts, o Serve as liaison between the grantees and the other NIH program staff, o Coordinate the projects activities with NIH-funded repositories and databases, to ensure the rapid and efficient distribution and long-term storage of biomaterials and data, o Assist in developing timetables for, and facilitating, the timely and wide distribution of biomaterials and data to the biomedical community, o Participate in data analysis, interpretations and, where warranted, co- author publications that report results of studies performed under this RFA. NICHD Project Officer: The NICHD will appoint a Project Officer, apart from the Project Scientist, who will: o carry out continuous review of all activities to ensure that the objective are being met and that all regulatory, fiscal, and administrative matters are handled according to NIH guidelines. o have the option to withhold support to a participating institution if technical performance requirements are not met. o Perform other duties normally required for program stewardship of grants. 3. Collaborative Responsibilities Steering Committee Functions: The Steering Committee (SC) will be the main governing body of the projects to be funded by this RFA. It will oversee and coordinate interactions among the projects, and will mediate interactions between the projects and the NIH. The SC will discuss scientific goals and progress, and recommend how mutant strains should be obtained, analyzed, and shared in order to be maximally valuable to all interested investigators. It will help to monitor the plans for sharing research resources. It will also address the recommendations made by the MSP. The SC will consist of the PIs of each of the projects, one or two NICHD Project Scientists, and a nonvoting independent chairperson. Each PI will have one vote and the NIH Project Scientist(s) will have a total of one vote. Mouse Genomics and Genetics Scientific Panel (MSP) Functions: The MSP coordinates activities among the projects, facilities and resources participating in NIH"s mouse mutagenesis and phenotyping initiative, including those to be funded in response to this RFA. The MSP uses its knowledge of the activities of all of the participating projects to ensure adequate investigation, communication and sharing, and to avoid redundant activities. It helps to coordinate activities that involve the mutagenesis, phenotyping, mapping, maintenance, and distribution and sharing of mutant mouse strains. The MSP evaluates and makes recommendations regarding the coordination of the activities of the projects that are funded by the mutagenesis and phenotyping initiatives, and other related activities that may be developed in the future. The MSP’s responsibilities include making recommendations that lead to exchanging mutants among the projects, sharing assay strategies, adopting common policies on data sharing, creating compatible databases, and other activities that will make these facilities of maximal utility to the scientific community. The MSP also sets standards for data format and nomenclature, as well as developing common guidelines and procedures for deposition of the primary phenotypic data, and for the preservation of mutant mouse strains. The committee consists of about 10 scientists who are not affiliated with any of the mutagenesis and phenotyping projects, and are not members of the advisory committees of those projects. Collectively, they have broad expertise in relevant topics such as developmental biology, reproduction, neurobiology, behavior, mutagenesis, phenotyping, mouse genetics, husbandry, genomics, and databases issues. The NIH Project Scientist(s) attend the MSP as non-voting members and act as a representative of the SC. The MSP meets at least once each year. 4. Arbitration Process Any disagreements that may arise in scientific or programmatic matters within the scope of the award between grantees and the NIH may be brought to arbitration. This special arbitration procedure in no way affects the awardee"s right to appeal an adverse action that is otherwise appealable in accordance with PHS regulations 42 CFR Part 50, Subpart D, and HHS regulation at 45 CFR Part 16. An Arbitration Panel will help resolve both scientific and programmatic issues that develop during the course of work that restrict progress. The Arbitration Panel will be composed of three members: a designee of the SC chosen without the NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two members. URLS IN NIH GRANT APPLICATIONS OR APPENDICES All applications and proposals for NIH funding must be self-contained within specified page limitations. Unless otherwise specified in an NIH solicitation, Internet addresses (URLs) should not be used to provide information necessary to the review because reviewers are under no obligation to review the Internet sites. Reviewers are cautioned that their anonymity may be compromised when they directly access an Internet site. PUBLIC ACCESS TO RESEARCH DATA THROUGH THE FREEDOM OF INFORMATION ACT The Office of Management and Budget (OMB) Circular A-110 has been revised to provide public access to research data through the Freedom of Information Act (FOIA) under some circumstances. Data that are (1) first produced in a project that is supported in whole or in part with Federal funds and (2) cited publicly and officially by a Federal agency in support of an action that has the force and effect of law (i.e., a regulation) may be accessed through FOIA. It is important for applicants to understand the basic scope of this amendment. NIH has provided guidance at: http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this RFA in a public archive, which can provide protections for the data and manage the distribution for an indefinite period of time. If so, the application should include a description of the archiving plan in the study design and include information about this in the budget justification section of the application. In addition, applicants should think about how to structure informed consent statements and other human subjects procedures given the potential for wider use of data collected under this award. LETTER OF INTENT Prospective applicants are asked to submit a letter of intent that includes a descriptive title of the proposed research, the name, address, telephone number, and e-mail address of the Principal Investigator, the identities of other key personnel and participating institutions, and the number and title of this RFA. Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows NICHD staff to estimate the potential review workload and plan the review. The letter of intent is to be sent to Dr. Steven Klein, at the address listed under INQUIRIES, below, by February 11, 2002. APPLICATION PROCEDURES The PHS 398 research grant application instructions and forms (rev. 5/2001) at http://grants.nih.gov/grants/funding/phs398/phs398.html are to be used in applying for these grants. This version of the PHS 398 is available in an interactive, searchable PDF format. Beginning January 10, 2002, the NIH will return applications that are not submitted on the 5/2001 version. For further assistance contact GrantsInfo, Telephone 301-710-0267, Email: GrantsInfo@nih.gov. Application Instructions Applicants must describe the project in the Research Plan section of the application within the normal page limitation (25 pages). The application’s Research Plan must include sections on: (1) overall purpose, strategy and plans, (2) phenotyping, (3) characterizing the mutations and the genes, (4) database/ bioinformatics, and (5) procedures for sharing research resources, including plans to exercise, or not to exercise, intellectual property rights (see SPECIAL REQUIREMENTS, above). However, if necessary, you may use up to five additional pages to describe the procedures for sharing mice, and phenotypic and genetic data (sections 4 and 5). This exception is made to enable a more complete description of these components, which are critical to the goals of this RFA. For the purpose of accomplishing the goals of this RFA, the project may include investigators at more than one site, and subcontracts may be included in the budget to support investigators at sites other than the awardee institution. Applications should define yearly milestones, which may be modified at the time of award. Budget requests should include travel funds for the PI and other critical staff to attend the SC meetings in the Bethesda, MD area twice per year. Submission Instructions The RFA label available in the PHS 398 (rev. 5/01) application form must be stapled to the bottom of the face page of the application and must display the RFA number, HD-01-020. A sample RFA label is available at http://grants.nih.gov/grants/funding/phs398/label-bk.pdf. Please note this is the pdf format. Failure to use this label could result in delayed processing of the application such that it may not reach the review committee in time for review. In addition, the RFA title and number must be typed on line 2 of the face page of the application form and the YES box must be marked. Submit a signed, typewritten original of the application, including the Checklist, and three signed photocopies, in one package to: CENTER FOR SCIENTIFIC REVIEW NATIONAL INSTITUTES OF HEALTH 6701 ROCKLEDGE DRIVE, ROOM 1040, MSC 7710 BETHESDA, MD 20892-7710 BETHESDA, MD 20817 (for express/courier service) At the time of submission, two additional copies of the application should be sent to: Director, Division of Scientific Review National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 5E03F, MSC 7510 Bethesda, MD 20892-7510 Rockville, MD 20852 (for express/courier service) Applications must be received by March 13, 2002. If an application is received after that date, it will be returned to the applicant without review. The Center for Scientific Review (CSR) will not accept any application in response to this RFA that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. CSR will not accept any application that is essentially the same as one already reviewed. This does not preclude the submission of substantial revisions of applications already reviewed, but such applications must include an introduction addressing the previous critique. REVIEW CONSIDERATIONS Upon receipt, applications will be reviewed for completeness by CSR, and for responsiveness to this RFA by NICHD. Incomplete and/or nonresponsive applications will be returned to the applicant without further consideration. Applications that are complete and responsive will be evaluated for scientific and technical merit by an appropriate peer review group convened by NICHD, in accordance with the review criteria stated below. These reviews will not include site visits. As part of the initial merit review, all applications will receive a written critique and may undergo a process in which only those applications deemed to have the highest scientific merit will be discussed, assigned a priority score, and receive a second level review by the National Advisory Child Health and Human Development Council. Review Criteria The goals of NIH-supported research are to advance our understanding of biological systems, improve the control of disease, and enhance health. In the written comments, reviewers will be asked to discuss the following aspects of the application in order to judge the likelihood that the proposed research will have a substantial impact on the pursuit of these goals. Each of these criteria will be addressed and considered in assigning the overall score, weighting them as appropriate for each application. Note that the application does not need to be strong in all categories to be judged likely to have major scientific impact and thus deserve a high priority score. For example, an investigator may propose to carry out important work that by its nature is not innovative, but is essential to move a field forward. o Significance: What will be the expected impact of the phenotypic and mapping information produced by the project on our understanding of the genetic bases of development and reproduction? o Approach: Does this study specify methodologies for phenotyping the mutants and for characterizing the mutations responsible for their defects? Is the conceptual framework for conducting phenotyping and mapping adequately developed, well integrated, and appropriate to the aims of the project? Will the proposed strategies enable identification of both dominant and recessive mutations that alter the processes of development and/or fertility? Does the applicant acknowledge potential problem areas and consider alternative tactics? o Innovation: Does the project employ novel concepts, approaches or methods? Are the aims original and innovative? Does the project challenge existing paradigms or develop new methodologies or technologies? o Investigator: Is the investigator appropriately trained and well suited to carry out this work? Is the work proposed appropriate to the experience level of the Principal Investigator and other researchers (if any)? o Environment: Does the scientific environment in which the work will be done contribute to the probability of success? Do the proposed experiments take advantage of unique features of the scientific environment or employ useful collaborative arrangements? Is there evidence of institutional support? Reviewers will also evaluate: o the response to the Research Objectives described above, o Integration with other resources: Are the plans adequate to ensure that the project will be able to obtain appropriate mutant strains? Are the plans adequate to integrate the mutants and the phenotypic data with those collected in other comparable projects? o Exportability and Accessibility: What is the likelihood that the mutant mouse strains developed and/or used in the project will be made widely available in a timely fashion to the scientific community? What is the likelihood that patentable research results, such as phenotypic and mapping information and methodologies, will be widely available for the scientific community, given the proposed plan to exercise, or not to exercise, intellectual property rights on those products? Does the project specify plans for creation of a highly efficient and organized bioinformatics database? Do the investigator"s quality control plans assure that databases provided to the wider scientific community will be accurate and highly efficient? In addition to the above criteria, in accordance with NIH policy, all applications will also be reviewed with respect to the following: o The reasonableness of the proposed budget and duration in relation to the proposed research. o The adequacy of the proposed protection for humans, animals or the environment, to the extent they may be adversely affected by the project proposed in the application. SCHEDULE Letter of Intent Receipt Date: February 11, 2002 Application Receipt Date: March 13, 2002 Peer Review Date: June 2002 Advisory Council Date: September 2002 Earliest Award Date: September 30, 2002 AWARD CRITERIA Factors that will be used to make award decisions are as follows: o Scientific and technical merit of the proposed project as determined by peer review, o Cost effectiveness of the proposed strategy, o Promise of the proposed project to accomplish the goals of this RFA, o Geographical distribution of projects, o Availability of funds. INQUIRIES Inquiries concerning this RFA are strongly encouraged. NICHD staff welcomes the opportunity to clarify issues or questions from potential applicants. Direct inquiries regarding programmatic issues to: Dr. Steven Klein Developmental Biology, Genetics and Teratology Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 4B01, MSC 7510 Bethesda, MD 20892-7510 Telephone: 301-496-5541 Fax: 301-480-0303 E-mail: kleins@exchange.nih.gov Dr. Tracy L. Rankin Reproductive Sciences Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8B01, MSC 7510 Bethesda, MD 20892-7510 Telephone: 301-435-6979 Fax: 301-480-2389 E-mail: tr44x@nih.gov Direct inquiries regarding fiscal matters to: Mr. Chris Myers Grants Management Branch National Institute of Child Health and Human Development 6100 Executive Boulevard, Room 8A17, MSC 7510 Bethesda, MD 20892-37510 Telephone: 301-435-6996 E-mail: myersc@exchange.nih.gov AUTHORITY AND REGULATIONS This program is described in the Catalog of Federal Domestic Assistance Nos. 93.864 and 93.865. Awards are made under authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and administered under NIH grants policies and Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. This program is not subject to the intergovernmental review requirements of Executive Order 12372 or Health Systems Agency review. The PHS strongly encourages all grant recipients to provide a smoke-free workplace and promote the non-use of all tobacco products. In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in some cases, any portion of a facility) in which regular or routine education, library, day care, health care, or early childhood development services are provided to children. This is consistent with the PHS mission to protect and advance the physical and mental health of the American people.


Weekly TOC for this Announcement
NIH Funding Opportunities and Notices



NIH Office of Extramural Research Logo
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS)
  USA.gov - Government Made Easy
NIH... Turning Discovery Into Health®



Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.