Department of Health and Human Services
National Institutes of Health (NIH), (http://www.nih.gov/)
Components of Participating Organizations
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). This FOA will be administered by the National Human Genome Research Institute (NHGRI, http://www.genome.gov/) on behalf of the NIH (http://www.nih.gov/). Other participating Institutes include:
National Center for Research Resources (NCRR), (http://www.ncrr.nih.gov)
National Eye Institute (NEI), (http://www.nei.nih.gov)
National Heart, Lung, and Blood Institute (NHLBI), (http://www.nhlbi.nih.gov/)
National Institute on Aging (NIA), (http://www.nia.nih.gov)
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.niams.nih.gov)
National Institute of Child Health and Human Development (NICHD), (http://www.nichd.nih.gov)
National Institute on Drug Abuse (NIDA), (http://www.nida.nih.gov)
National Institute of Deafness and Other Communication Disorders (NIDCD), (http://www.nidcd.nih.gov)
National Institute of Dental and Craniofacial Research (NIDCR), (http://www.nidcr.nih.gov)
National Institute of Environmental Health Sciences (NIEHS), (http://www.niehs.nih.gov)
National Institute of General Medical Sciences (http://www.nigms.nih.gov)
National Institute of Mental Health (NIMH), (http://www.nimh.nih.gov)
National Institute of Neurological Disorder and Stroke (NINDS), (http://www.ninds.nih.gov)
Title: Knockout Mouse Phenotyping Project Database (U54)
Update: The following update relating to this announcement has been issued:
Release Date: September 10, 2010
Letters of Intent Receipt Date(s): September 15, 2010
Application Receipt Dates(s): November 10, 2010
Peer Review Date(s): February, 2011
Council Review Date(s): May, 2011
Earliest Anticipated Start Date:July, 2011
Additional Information To Be Available Date (Url Activation Date): N/A
Expiration Date:November 11, 2010
Due Dates for E.O. 12372
Table of Contents
I Overview Information
Part II Full Text of Announcement
Section I. Funding Opportunity Description
1. Research Objectives
Section II. Award Information
1. Mechanism(s) of Support
2. Funds Available
Section III. Eligibility Information
1. Eligible Applicants
A. Eligible Institutions
B. Eligible Individuals
2.Cost Sharing or Matching
3. Other - Special Eligibility Criteria
Section IV. Application and Submission Information
1. Address to Request Application Information
2. Content and Form of Application Submission
3. Submission Dates and Times
A. Receipt, Review and Anticipated Start Dates
1. Letter of Intent
B. Sending an Application to the NIH
C. Application Processing
D. Application Assignment
4. Intergovernmental Review
5. Funding Restrictions
6. Other Submission Requirements
Section V. Application Review Information
2. Review and Selection Process
3. Anticipated Announcement and Award Dates
Section VI. Award Administration Information
1. Award Notices
2. Administrative and National Policy Requirements
A. Cooperative Agreement Terms and Conditions of Award
1. Principal Investigator Rights and Responsibilities
2. NIH Responsibilities
3. Collaborative Responsibilities
4. Dispute Resolution Process
Section VII. Agency Contact(s)
1. Scientific/Research Contact(s)
2. Peer Review Contact(s)
3. Financial/ Grants Management Contact(s)
Section VIII. Other Information - Required Federal Citations
Part II - Full Text of Announcement
1. Research Objectives
The NIH plans to support the Knockout Mouse Phenotyping Project (KOMP2) by creating a research network to produce a comprehensive phenotype resource of mouse mutants made from the IKMC knockout mouse mutants which contains an ES cell knockout for every gene in the mouse genome. The phenotyping effort will include a broad-based unbiased set of tests. Each component of the research network will be responsible for tracking its status in generating the mouse mutants or producing phenotype data of genes assigned to it. The purpose of this FOA is to solicit applications to develop and implement a Data Coordination Center and Database (DCCDB) to serve as a centralized resource to provide overall tracking of KOMP2 and to deliver this information to the research network, NIH staff, and the public.
This FOA is being issued to enhance the value of the mouse as a powerful and important tool in the study of human disease. The mouse has long been an important mammalian model system for the study of mammalian gene function. Mouse mutants with phenotypes that mimic human traits have served as critical research tools in understanding the genetics underlying mammalian biology. Because of its importance to human biology, mapping and sequencing the genome of mouse strain C57BL/6 was carried out as part of the Human Genome Project. Another major genomic resource for mouse research was developed by the Mammalian Gene Collection (MGC) project (http://mgc.nci.nih.gov/), which as of December 2009 included 27,285 full-ORF (open reading frame) cDNA clones representing 17,701 individual mouse genes. Equally important, mouse mutants have been the tools used to begin to understand gene function and pathways as the field has moved from gene identification to mammalian functional genomics.
To complement the mouse genome sequence and full-length cDNA collection, it was recognized in 2003 that a defined genetic resource that can be used to elucidate gene function was needed. At that time a proposal was made to establish a focused, large-scale international effort to produce a publicly available, comprehensive collection of mouse knockout mutants, i.e. a library containing a null mutation in every gene in the mouse genome (Austin, C.P., et al. Nature 36, 921-924 (2004)). It was recommended that this be accomplished in a phased production approach, beginning with the construction of a resource of ES cells comprising a comprehensive collection of null and conditional alleles. This would be followed by the construction of mice from the ES cells and then phenotyping the mice with an increasingly sophisticated set of tests. Tier 1, or basic phenotyping, would be done on nearly all of the mice created by the project. Tier 2, microarray and transcriptome based phenotyping, would be carried out on a subset of these mice. Subsequent specialized phenotyping and further in depth analyses on specific mice would then be pursued as part of individual research programs.
There followed a number of international efforts that further defined the proposed knockout mouse resource. Following a March 2005 workshop which endorsed the concept (http://www.genome.gov/15014549), the NIH launched the Knockout Mouse Project (KOMP) to generate knockout (null) mutations in 8,500 genes in C57BL/6 knockout mice lines by deleting all or most of the exons in target genes (Valenzuela, D.M., et al., Nature Biotechnology 6, 652-659 (2003)) or knockout-first conditional ready alleles (Testa, G., et al., Genesis 38, 151-158 (2004)). As of the end of June 2010, KOMP had produced knockouts of about 5,500 genes and is on target to complete the goal of producing 8,500 knockout mutant ES cell lines by the end of 2011. In parallel, the European Conditional Mouse Mutagenesis Program (EuCOMM) and the North American Conditional Mouse Mutagenesis Program (NorCOMM) are on track to complete their goals of producing an additional 9,000 knockout mice by the end of 2011. The three programs will thus produce a comprehensive resource of mutant mouse ES cell lines. They have coordinated their efforts through the formation of the International Knockout Mouse Consortium (IKMC) (http://www.knockoutmouse.org/).
The NIH KOMP included establishment of a repository to archive, maintain, and distribute high quality ES cell clones, as well as live mouse lines, frozen embryos and sperm, and vectors (www.komp.org). As part of the repository’s quality control procedures, it is generating live mice from a fraction of the ES cells as they are generated. The original KOMP goal was to generate 500 mouse lines during the course of the program; current efforts are exceeding that goal. To date, 413 lines of mice have been generated and, at current production rates, about 850 strains will be produced by the end of 2011.
Thus, the first phase of the proposed resource is on schedule to be completed by 2011, and attention has now turned toward implementation of the second phase. Over the past year, there have been a number of discussions to plan a potential mouse phenotyping effort. The NIH held a KOMP Phenotyping Conference in Bethesda, MD in October 2009, at which a group of researchers representing diverse scientific backgrounds expressed their unanimous enthusiasm and support for a proposed effort to conduct high-throughput and comprehensive phenotyping of the resource being produced by the members of the IKMC (meeting report available at www.komp.org). The meeting attendees were supportive of a proposed strategy to first convert ES cells into mice at one or more high-throughput facilities that can also efficiently conduct highly informative preliminary analyses (e.g., LacZ expression, stage of embryonic lethality, fecundity), followed by performance of a defined set of standard broad-based phenotype tests at KOMP2 phenotyping facilities. The phenotyping data would be rapidly and freely released to the public as they are generated, with the mice being archived for distribution to the research community. The meeting participants stressed that any U.S. phenotyping effort must be coordinated with comparable efforts elsewhere (similar discussions and plans are being made in Europe, Canada, and Asia). The standard phenotyping tests, analyses, and examinations that are included in the KOMP2 resource effort should be chosen primarily on the basis of their reliability, power, and likelihood to reveal disease and human clinical relevance. These recommendations were highly similar to those that have come from other efforts to solicit input from the US national research community.
The first large-scale public phenotyping effort was funded by the European Commission (EC) in 2008. The European Mouse Disease Clinic (EUMODIC, http://www.eumodic.org/) program is comprised of 4 mouse phenotyping centers, whose goals are to provide phenotype information on 500 EUCOMM, NorCOMM and KOMP knockout mouse lines by 2011, using a common phenotyping protocol developed by the European Mouse Phenotyping Resource of Standardized Screens (EMPReSS, http://empress.har.mrc.ac.uk/) developed by the European Union Mouse Research for Public Health and Industrial Applications (EUMORPHIA) Program. This data is made accessible through a separately funded database, EUROPHENOME (http://www.europhenome.org/). It is expected that the NIH will ask successful applicants to this FOA to coordinate their efforts with the EUMODIC programs and the currently forming International Mouse Phenotyping Consortium (IMPC), to select, harmonize phenotyping data platforms, and make use of prior know-how and experience (http://commonfund.nih.gov/KOMP2/ipmc-policies.asp).
Each of the funded experimental projects, both mouse production and phenotyping, is expected to have its own independent informatics resources to track progress and provide this information to a centralized database. The purpose of the DCCDB is to collect all relevant information from the production/phenotyping efforts, harmonize data and maintain data quality, so other investigators and the public can gain access to the information at a single site.
At this time, the precise nature of the experimental approach(es) that will be taken by the phenotyping effort has not been specified. As described in RFA-RM-10-013, to which potential applicants to this FOA are referred for more details, the NIH's long-term objective is to generate a collection of null mutants marked with a reporter and collect phenotype information on at least 8,500 genes as part of a world-wide effort to study each of the projected 20,000 genes in the mouse genome. At present, there are a range of tests that can be considered for use in attaining or making significant progress towards this goal.
The purpose of this FOA is to solicit applications for a project to develop and implement the Data Coordination Center and Database (DCCDB) component of the KOMP2 research network. The four key components likely needed for the KOMP2 Network and informatics infrastructure in the DCCDB include:
Collaborations with Centers: It is anticipated that applications responsive to this FOA will need to work closely with the mouse centers generating the data in order to facilitate data transfer, track data and metadata, ensure quality control, implement new tests and integrate software and to deliver data in a timely fashion and in appropriate formats to a centralized database.
Data Coordination Center Database: The DCCDB must include the functionalities of a tracking database and a database management system to allow internal users and NIH staff to follow progress of projects in the pipeline, using a web based plaform. It will be critical for production groups and NIH staff to be able to produce live reports of steps in the pipeline for tracking and monitoring purposes. For example, a query may ask for the set of all genes that have completed all phenotyping and return a number of genes and their unique identifiers in a format that includes the ability to click on any gene and go to the data sets.
Data Quality Control and Annotation. The application should describe data QC procedures for assays employed in the phenotyping platforms and the frequency of the QC. The DCCDB will perform annotation of the data, employing standard phenotype ontologies, in order to facilitate searches.
International outreach. The efforts of the DCCDB should not duplicate the informatics efforts of other international projects for generating and analyzing null or conditional null mice. However, it will be important for KOMP2 to have access to information from, and provide information to these related efforts, such as EUMODIC and the IDCC. It is expected that the NIH will ask successful applicants to this FOA to coordinate their efforts with the EUMODIC programs and the currently forming International Mouse Phenotyping Consortium (IMPC).
Data Archive: The DCCDB should plan to transfer the contents of the database to a permanently funded data warehouse/archive, including but not limited to NCBI.
Applicants or groups that have developed a database or database components that can perform some or large portions of the requirements stated in this FOA will be considered responsive if they can demonstrate clearly that the work that they propose is a major valued added to existing systems, and that they can demonstrate that there is no functional overlap or redundancy with other funding for such projects.
Management Plan. The application should describe the management plan for the proposed project and how it will support the achievement of the proposed goals. The plan should also describe how the DCCDB will interact with the various components of KOMP2. Coordination of the awardees’ activities with the informatics efforts of other international efforts to produce and study mouse knockouts must be described.
In summary, applicants for awards under this FOA:
VIII, Other Information - Required Federal Citations, for policies related to
Section II. Award Information
1. Mechanism of Support
This funding opportunity will use the U54 award mechanism(s).
This FOA uses “Just-in-Time” information concepts. It also uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).
This funding opportunity will use a cooperative agreement award mechanism. In the cooperative agreement mechanism, the Project Director/Principal Investigator (PD/PI) retains the primary responsibility and dominant role for planning, directing, and executing the proposed project, with NIH staff being substantially involved as a partner with the Principal Investigator, as described under the Section VI. 2. Administrative Requirements, "Cooperative Agreement Terms and Conditions of Award". The funding opportunity may be continued for an additional five year period, depending on the results of a program review in the 3rd or 4th year of the initial project, but new FOAs will be issued rather than accept applications for a renewal of this FOA.
2. Funds Available
the nature and scope of the proposed research will vary from application to
application, it is anticipated that the size and duration of each award will
also vary. Although the financial plans of the IC(s) provide support for this
program, awards pursuant to this funding opportunity are contingent upon the
availability of funds and the receipt of a sufficient number of meritorious
Facilities and administrative costs requested by consortium participants are not included in the direct cost limitation, see NOT-OD-05-004.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Section III. Eligibility Information
1. Eligible Applicants
1.B. Eligible Individuals
Any individual with the skills, knowledge, and resources necessary to carry out the proposed research as the PD/PI is invited to work with his/her institution to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH program support.
More than one PD/PI, or multiple PDs/PIs, may be designated on the application for projects that require a “team science” approach and therefore clearly do not fit the single-PD/PI model. Additional information on the implementation plans, policies and procedures to formally allow more than one PD/PI on individual research projects is available at http://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior to the submission of the application (see http://grants.nih.gov/grants/ElectronicReceipt/preparing.htm for instructions).
The decision of whether to apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility of the investigators and applicant organizations, and should be determined by the scientific goals of the project. Applications for grants with multiple PDs/PIs will require additional information, as outlined in the instructions below. When considering multiple PDs/PIs, please be aware that the structure and governance of the PD/PI leadership team as well as the knowledge, skills and experience of the individual PDs/PIs will be factored into the assessment of the overall scientific merit of the application. Multiple PDs/PIs on a project share the authority and responsibility for leading and directing the project, intellectually and logistically. Each PD/PI is responsible and accountable to the grantee organization, or, as appropriate, to a collaborating organization, for the proper conduct of the project or program, including the submission of required reports. For further information on multiple PDs/PIs, please see http://grants.nih.gov/grants/multi_pi.
Principal Investigator (P.I.) Effort. The effective management of a coordination project of this scale requires a significant commitment by the P.I. The P.I. of a large-scale project funded under this FOA is expected to devote at least 2.4 (CY) person months to the project. Additionally, it will be helpful for the applicant to describe how he/she envisions managing the proposed project, and how that management will support achievement of the proposed goals and milestones. Useful elements of this description include the organization of the proposed production effort, its management structure, including integration of the separate components to form an efficient pipeline, key personnel, section leaders, and reporting relationships. Recruitment and training of personnel may also be discussed. The plan should also describe how the various components of the proposed production effort will be integrated, and how collaborations or subcontracts, if proposed, will be managed.
2. Cost Sharing or Matching
program does not require cost sharing as defined in the current NIH Grants Policy
3. Other-Special Eligibility Criteria
Number of Applications. Applicants may submit more than one application, provided they are scientifically distinct.
Resubmissions. Resubmission applications are not permitted in response to this FOA.
Renewals. Renewal applications are not permitted in response to this FOA.
1. Address to
Request Application Information
The current PHS 398 application instructions are available at http://grants.nih.gov/grants/funding/phs398/phs398.html in an interactive format. Applicants must use the currently approved version of the PHS 398. For further assistance contact GrantsInfo, Telephone (301) 710-0267, Email: GrantsInfo@nih.gov.
Telecommunications for the hearing impaired: TTY 301-451-5936.
2. Content and Form of Application Submission
Prepare all applications using the PHS 398 application forms and in accordance with the PHS 398 Application Guide (http://grants.nih.gov/grants/funding/phs398/phs398.html).
Applications must have a D&B Data Universal
Numbering System (DUNS) number as the universal identifier when applying for
Federal grants or cooperative agreements. The D&B number can be obtained by
calling (866) 705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should
be entered on line 11 of the face page of the PHS 398 form.
The title and number of this funding opportunity must be typed in item (box) 2 only of the face page of the application form and the YES box must be checked.
Organizations (Non-domestic (non-U.S.) Entity)
NIH policies concerning grants to foreign (non-U.S.) organizations can be found in the NIH Grants Policy Statement at: http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part12.htm#_Toc54600260.
Applications from foreign organizations must:
In addition, for applications from foreign organizations:
Proposed research should provide special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions in other countries that are not readily available in the United States or that augment existing U.S. resources.
Applications with Multiple PDs/PIs
When multiple PD/PIs are proposed, use the Face Page-Continued page to provide items 3a – 3h for all PD/PIs. NIH requires one PD/PI be designated as the “contact PD/PI” for all communications between the PD/PIs and the agency. The contact PD/PI must meet all eligibility requirements for PD/PI status in the same way as other PD/PIs, but has no special roles or responsibilities within the project team beyond those mentioned above. The contact PD/PI may be changed during the project period. The contact PD/PI should be listed in block 3 of Form Page 1 (the Face Page), with all additional PD/PIs listed on Form Page 1-Continued. When inserting the name of the PD/PI in the header of each application page, use the name of the “Contact PD/PI, et. al.” The contact PD/PI must be from the applicant organization if PD/PIs are from more than one institution.
All individuals designated as PD/PI must be registered in the eRA Commons and must be assigned the PD/PI role in that system (other roles such as SO or IAR will not give the PD/PI the appropriate access to the application records). Each PD/PI must include their respective eRA Commons ID in the eRA Commons User Name field.
Multiple PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the section of the Research Plan entitled, “Multiple PD/PI Leadership Plan”, must be included. A rationale for choosing a multiple PD/PI approach should be described. The governance and organizational structure of the leadership team and the research project should be described, and should include communication plans, process for making decisions on scientific direction, and procedures for resolving conflicts. The roles and administrative, technical, and scientific responsibilities for the project or program should be delineated for the PDs/PIs and other collaborators.
If budget allocation is planned, the distribution of resources to specific components of the project or the individual PDs/PIs should be delineated in the Leadership Plan. In the event of an award, the requested allocations may be reflected in a footnote on the Notice of Award (NoA).
Additional information is available in the PHS 398 grant application instructions.
Submission Dates and Times
Applications must be received on or before the receipt date described below (Section IV.3.A). Submission times N/A.
3.A. Receipt, Review and Anticipated Start Dates
Letter of Intent Receipt Date(s): September 15, 2010
Application Receipt Date(s):November 10, 2010
Peer Review Date(s): February, 2011
Council Review Date(s): May, 2011
Earliest Anticipated Start Date(s): July, 2011
Letter of Intent
Prospective applicants are asked to submit a letter of intent that includes the following information:
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 IC staff to
estimate the potential review workload and plan the review.
The letter of intent is to be sent by the date listed in Section IV.3.A.
The letter of intent should be sent to:
Division of Extramural Research
National Human Genome Research Institute
5635 Fishers Lane
Bethesda, MD 20892
Telephone: (301) 496-7531
3.B. Sending an Application to the NIH
must be prepared using the forms found in the PHS 398 instructions for
preparing a research grant application. 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 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
Personal deliveries of applications are no longer permitted (see http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-040.html).
At the time of submission, two additional copies of the
application and all copies of the appendix material must be sent to:
Ken Nakamura, Ph.D
Office of Scientific Review
National Human Genome Research Institute
5635 Fishers Lane
Bethesda MD 20892
Telephone: (301) 496-7531
Applications must be received on or before the application receipt date described above (Section IV.3.A.). If an application is received after that date, the application may be delayed in the review process or not reviewed. Upon receipt, applications will be evaluated for completeness by the CSR and for responsiveness by the reviewing Institute. Incomplete and/or non-responsive applications will not be reviewed.
The NIH will not accept any application in response to this funding opportunity that is essentially the same as one currently pending initial review, unless the applicant withdraws the pending application. However, when a previously unfunded application, originally submitted as an investigator-initiated application, is to be submitted in response to a funding opportunity, it is to be prepared as a NEW application. That is, the application for the funding opportunity must not include an Introduction describing the changes and improvements made, and the text must not be marked to indicate the changes from the previous unfunded version of the application.
Information on the status of an application should be checked by the Principal Investigator in the eRA Commons at: https://commons.era.nih.gov/commons/.
4. Intergovernmental Review
This initiative is not subject to intergovernmental
5. Funding Restrictions
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The Grants Policy Statement can be found at NIH Grants Policy Statement.
are allowable. A grantee may, at its own risk and without NIH prior approval,
incur obligations and expenditures to cover costs up to 90 days before the
beginning date of the initial budget period of a new award if such costs: 1)
are necessary to conduct the project, and 2) would be allowable under the
grant, if awarded, without NIH prior approval. If specific expenditures would
otherwise require prior approval, the grantee must obtain NIH approval before
incurring the cost. NIH prior approval is required for any costs to be incurred
more than 90 days before the beginning date of the initial budget period of a
The incurrence of pre-award costs in anticipation of a competing or non-competing award imposes no obligation on NIH either to make the award or to increase the amount of the approved budget if an award is made for less than the amount anticipated and is inadequate to cover the pre-award costs incurred. NIH expects the grantee to be fully aware that pre-award costs result in borrowing against future support and that such borrowing must not impair the grantee's ability to accomplish the project objectives in the approved time frame or in any way adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part6.htm.)
Special Guidance for Applicants
Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI.2.A "Award Administration Information".
The NHGRI has conducted several competitions for large-scale projects and it has been NHGRI’s experience that there are specific information items and presentation formats that the reviewers have found to be critical for their ability to assess proposals for such efforts effectively. The following guidance summarizes that experience in the form of a format that which the applicant may use to provide that information. If there is additional information, not addressed in this Guidance, that the applicant wishes to present, s/he is encouraged to provide it in a concise form, in addition to the information requested here.
6.I The Research Proposal. This section comprises the applicant's description for a production project to provide a Data Coordination Center Database holding information derived from broad-based phenotyping assays on hundred(s) of knockout mice lines per year developed from the IKMC program. The organization suggested below for this section of the application is based on the NIH staff's current understanding of the steps in this processes. The applicant is free to propose an alternative strategy but, in so doing, must address all of the issues raised below.
6.I.1. Data Coordination Center Database: The data being tracked by the DCCDB should include, but are not limited to, a variety of information types relating to the production status of mutants (from ES cell selection through to production of mice) and the locations of ES cells or mice in NIH-supported repositories. It will compile and track several lists of mouse genes – those that have been mutated and for which ES cells, frozen embryos, sperm or mice are available to investigators, those that have entered into the mutation production and phenotyping pipelines and their status in the pipeline, and those that remain to be taken up by the pipeline. This functionality must allow scanning across the database not just the following of individual mice. Metadata collection, including a timestamp on all data sets will be vital to allow proper tracking of progress and retrospective analysis of the projects.
The DCCDB will also collect phenotype data. It is anticipated that multiple data types will be involved, including but not limited to numerical data, image data, graphical data representations and annotation of data, thus the user interface and visualization tools must account for these data types and be adaptable for future improvements in data visualization and manipulation. It is anticipated that there could be the need for displays of MRI data, CT data, ultrasound, images, movies, histopathology, FACS, NMR and the flexibility to include additional data types and phenotypic test in the future. The viewing of the data and manipulation should occur for the most part with tools available on the web portal. The functionality of the database should allow searching by phenotype, including complex searches that allow users to “dial in” their precise multi-parameter searches. For example, a search to show all mice and/or targets that have a 20% increase in body weight, a 50% increase in lipid levels and 25% decrease in glucose. The searching features should allow users to select a significant number of parameters, define numerical ranges, or % changes, or standard deviation or p-values. The user should be able to compare with WT controls or historical data. A method of downloading large datasets from DCCDB should be included so that users can acquire and analyze all or large parts of the data. The application should include information on how efficient and unencumbered access to the DCCDB will be maintained. The efforts of the DCCDB should be focused on collecting, tracking and distributing relevant information for the KOMP2 project, and should not duplicate the informatics efforts of other projects funded to describe the characteristics or functions of mouse genes. However, it will be important for the information in the DCCDB to be accessible to other such projects. Thus, the applicant also should describe how information from the DCCDB will be transferred or linked to other mouse informatics resources including, but not limited to, the UCSC Genome Browser, ENSEMBL, NCBI, and Mouse Genome Informatics, as well emerging databases on human disease related genes.
6.I.2. Data Quality Control and Annotation. The application should describe data QC procedures for each assay employed in the phenotyping platforms and the frequency of the QC. The annotation of data and the need for controlled vocabularies and structured ontologies will be needed to make the data accessible and comparable from different centers over the time of the project. This is likely a task that is beyond the DCC scope to develop de novo and may require working with other groups and being able to integrate and incorporate such developments, thus the applicant should address the plans to accommodate such functionalities. BioPortal (http://bioportal.bioontology.org/) is a good example of an existing system to access and share ontologies that are publicly available and widely used. One requirement will be that the applicant follow the rules and guidelines established by the International Committee on Standardized Genetic Nomenclature for Mice.
6.I.3. International outreach. Thus, the DCCDB will also serve the KOMP2 Research Network as a central information resource regarding other publicly available null and conditional mouse mutations by obtaining information from the several other projects around the world that have or will be established to generate targeted null and conditional mutations and phenotyping in the mouse genome. In sum, the DCCDB will provide links to all groups funded through the KOMP2 Research Network, put in place mechanisms to export data to and receive data from other mouse informatics resources, and provide a public website through which all of this information will be made available.
6.I.4. Data Archive: The DCCDB should plan to transfer the contents of the database to a permanently funded data warehouse, including but not limited to NCBI. For example, it is anticipated that the DCCDB could work with NCBI to deliver data in formats and procedures similar to dbGaP (http://www.ncbi.nlm.nih.gov/gap). It is recognized that both parties, the DCCDB and NCBI, will need to await further development of the KOMP2 and DCCDB to make more precise plans but information relating to dbGaP submission can be found at http://www.nature.com/ng/journal/v39/n10/full/ng1007-1181.html
6.I.5. Technology Development. The applicant should address any experience that s/he has had in developing and improving technology for mouse phenotype data collection and maniputlation.
6.I.6. Prior experience in attaining milestones. The applicant should discuss his/her experience in defining and meeting useful milestones and budgets for a information technology/database effort.
6.II. Technology development. The Research Plan should include a separate section describing plans for technology development efforts to improve the efficiency of the proposed project.
6.III. Budget Request. The budget requested must be described clearly and be well justified. Applicants should submit the Detailed Budget for the Initial Budget Period (page 4 of PHS-398) and the Budget for Entire Proposed Period of Support (page 5 of PHS-398)
PHS398 Research Plan Sections
All application instructions outlined in the PHS398 Application Instructions are to be followed, with the following additional requirements:
This FOA uses non-modular budget formats described in the PHS 398 application instructions (see http://grants.nih.gov/grants/funding/phs398/phs398.html).
All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. See NOT-OD-06-096.
All paper PHS 398 applications submitted must provide appendix material on CDs only. Include five identical CDs in the same package with the application. See http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-031.html.
Do not use the Appendix to circumvent the page limitations. An application that does not observe the required page limitations may be delayed in the review process.Resource Sharing Plan(s)
NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this should be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.
(a) Data Sharing Plan: Investigators seeking $500,000 or more in direct costs in any year are expected to include a brief 1-paragraph description of how final research data will be shared, or explain why data-sharing is not possible. Applicants are encouraged to discuss data-sharing plans with their NIH program contact. See Data-Sharing Policy or http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-032.html.
(b) Sharing Model Organisms: Regardless of the amount requested, all applications where the development of model organisms is anticipated are expected to include a description of a specific plan for sharing and distributing unique model organisms and related resources, or state appropriate reasons why such sharing is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.
(c) Genome-Wide Association Studies (GWAS): Regardless of the amount requested, applicants seeking funding for a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. A genome-wide association study is defined as any study of genetic variation across the entire genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight) or the presence or absence of a disease or condition. For further information see Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.
All applications are expected to include a plan for sharing research data. The standard NIH data sharing policy is available at http://grants.nih.gov/grants/policy/data_sharing. All investigators responding to this funding opportunity should include a description of how final research data will be shared, or explain why data sharing is not possible. However, rapid release of the data would be of benefit to the scientific user community because of the scope of this community resource project as described in this FOA and because of the national and scientific investment that the NIH will make in KOMP2. Accordingly, applicants should not feel constrained by the standard approach to data sharing but should display and promote innovative methods for achieving the maximum use of the KOMP2 resource.
Data release. Applicants should be familiar with the NIH statements regarding sharing of resources developed with Federal funds (http://grants.nih.gov/grants/intell-property_64FR72090.pdf). In the case of phenotypic data, plans for the dissemination and access of the data to a centralized database is needed in line with the aims of the FOA. With regard to the present solicitation, NHGRI and the other participating Institutes have identified the goal of the KOMP2 as the production of a “community materials” as described in the proceedings of the Meeting on Sharing Data from Large-Scale Biological Research Projects (http://www.wellcome.ac.uk/doc_wtd003208.html). Therefore, responses to this FOA should propose a specific and comprehensive plan for the rapid release of data resulting from the knockout mouse production and phenotyping effort to the appropriate databases. A single separately funded database will provide public access to all phenotyping data from all the centers funded in KOMP2. Applications proposing to cooperate with only one or a few centers will be considered nonresponsive to this FOA. The quality of this plan will be an important criterion in the award of the cooperative, and an appropriate plan for release of data and materials will be made a condition of the awards made as a result of this FOA.
In presenting the data release plan, the release of data to the project's public website should be discussed and should include, but is not limited to: information as to the genes that have been assigned to the project, when the effort to study the mice is scheduled to begin or actually began, data that confirm a knockout mouse has been successfully made, date that data were collected and shipped to a central phenotyping database, and other pertinent data.
Additionally, the applicant's data release plan should address how software or technology improvements developed under this funding will be publicly released. It is highly likely that software solutions and LIMS system development would benefit the other IMPC phenotyping centers as well as other investigators.
The release plans are expected to fully address how the end users of the mice, embryos, data, and other materials generated by the funded activity, in both the public and private sectors, will be fully enabled to share and use the data, consistent with achieving the goals of this project.
The reviewers will assess the reasonableness of the data sharing plan or the rationale for not sharing research data. Program staff of the funding organization, when making recommendations about funding applications, will consider the adequacy of the resources sharing plan and any related data sharing plans. Section I. “Research Objectives” contains a section entitled “Data and Materials Release” that addresses the issues that can be used in a data-sharing plan for a KOMP2 component.
Sharing Research Resources
NIH policy expects that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm and http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part7.htm - _Toc54600131). Investigators responding to this funding opportunity should include a plan for sharing research resources addressing how unique research resources will be shared or explain why sharing is not possible. However, as indicated in the previous section with respect to the data sharing plan, applicants should not feel constrained to propose a standard plan for sharing materials, given the scope of KOMP2 as defined by the FOA and the NIH's investment in this project. Widespread dissemination and access to the materials generated through this program to the public and private research sectors are an aim of this FOA and will require innovative methods for achieving the maximum use of the resource to be produced under this project.
Program staff of the funding organization, when making recommendations about funding applications, will consider the adequacy of the resources sharing plan and any related data sharing plans. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, http://grants.nih.gov/grants/funding/2590/2590.htm). See Section VI.3. Reporting.
Specific Instructions for Foreign Applications
All foreign applicants must complete and submit budget requests using the Research & Related Budget component found in the application package for this FOA. SeeNOT-OD-06-096.
Only the review criteria described below will be considered in the review process.
2. Review and Selection Process
Applications that are complete and responsive to the FOA will be evaluated for scientific and technical merit by an appropriate peer review group convened by NHGRI and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.
As part of the scientific peer review, all applications will:
The mission of the NIH is to support science in pursuit of knowledge about the biology and behavior of living systems and to apply that knowledge to extend healthy life and reduce the burdens of illness and disability. As part of this mission, applications submitted to the NIH for grants or cooperative agreements to support biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact/priority score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following five scored review criteria, and additional review criteria (as applicable for the project proposed).
Scored Review Criteria
Reviewers will consider each of the five review criteria below in the determination of scientific and technical merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Significance. Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Innovation. Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Approach. Are the overall strategy, methodology, and
analyses well-reasoned and appropriate to accomplish the specific aims of the
project? Are potential problems, alternative strategies, and benchmarks
for success presented? If the project is in the early stages of
development, will the strategy establish feasibility and will particularly
risky aspects be managed?
If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?
Environment. Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?
Additional Review Criteria
As applicable for the project proposed, reviewers will consider the following additional items in the determination of scientific and technical merit, but will not give separate scores for these items.
Protections for Human Subjects. For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials.
Inclusion of Women, Minorities, and Children. When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children.
Vertebrate Animals. The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information, see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.
Biohazards. Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
Resubmission Applications. Resubmissions are not applicable to this FOA.
Renewal Applications. Renewals are not applicable to this FOA.
Revision Applications. Revisions are not applicable to this FOA.
Additional Review Considerations
As applicable for the project proposed, reviewers will address each of the following items, but will not give scores for these items and should not consider them in providing an overall impact/priority score.
Applications from Foreign Organizations. Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Select Agents Research. Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Resource Sharing Plans. Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan (http://grants.nih/gov/grants/policy/data_sharing/data_sharing_guidance.htm); 2) Sharing Model Organisms (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-042.html); and 3) Genome Wide Association Studies (GWAS) (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html).
Budget and Period Support. Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
The following will be considered in making funding decisions:
NIH considers the following in evaluating Center grant applications:
3. Anticipated Announcement and Award Dates
1. Award Notices
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.
If the application is under consideration for funding,
NIH will request "just-in-time" information from the applicant. For
details, applicants may refer to the NIH Grants Policy
Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General.
formal notification in the form of a Notice of Award (NoA) will be
provided to the applicant organization. The NoA signed by the grants management
officer is the authorizing document. Once all administrative and programmatic
issues have been resolved, the NoA will be generated via email notification
from the awarding component to the grantee business official.
Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs. See Also Section IV.5. Funding Restrictions.
2. Administrative and National Policy Requirements
All NIH grant
and cooperative agreement awards include the NIH Grants Policy Statement as
part of the NoA. For these terms of award, see the NIH Grants Policy Statement
Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_Part4.htm) and Part II Terms and
Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific
Types of Grants, Grantees, and Activities (http://grants.nih.gov/grants/policy/nihgps_2003/NIHGPS_part9.htm).
The following Terms and Conditions will be incorporated into the award statement and will be provided to the Principal Investigator as well as to the appropriate institutional official, at the time of award.
2.A. Cooperative Agreement Terms
and Conditions of Award
The following special terms of award are 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 cooperative agreement an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients 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 awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
2. A.1. Principal Investigator Rights and Responsibilities
The Principal Investigator will have the primary responsibility for defining the details for the data coordination and database project within the guidelines of FOA RM-10-011, -012 and -013 and for performing the scientific activities. The P.I. will agree to collaboration with the other members of the KOMP2 Research Network and to accept close coordination, cooperation, and participation of NIH staff and advisors in those aspects of scientific and technical management of the project as described under 2.A.2. NIH Responsibilities
The P.I. will:
will retain custody of and have primary rights to the data and software
developed under these awards, subject to Government rights of access consistent
with current HHS, PHS, and NIH policies.
2. A.2. NIH Responsibilities
An NIH Project Scientist will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below.
For the KOMP2 Research Network, a Project Scientist will be appointed from each of the Institutes that is responsible for the participating cooperative agreements, that is, NHGRI and NCRR.
For RFA-RM-10-012 (this FOA), the NHGRI Project Scientist will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination. However, the role of the NHGRI Project Scientist will be to facilitate and not to direct the activities. It is anticipated that decisions in all collaborative activities will be reached by consensus of the KOMP2 Steering Committee, of which the PI is a member, and that the NHGRI Project Scientist will participate in this process. The NHGRI Project Scientist shall participate as a member of the Steering Committee and will have one vote.
The Project Scientist will:
2.A.3. Collaborative Responsibilities
The KOMP2 Research Network will involve three distinct activities (generation of the knockout mouse resource, a data coordination center, KOMP2 phenotyping centers); funding of these activities will be solicited by a set of set of three FOAs (RFA-RM-10-012 (the current FOA), RFA-RM-10-011, RFA-RM-10-013). All components of the KOMP2 program will be funded by cooperative agreements and a single Steering Committee (section 2.A.3) and a single Panel of Scientific Consultants (section 2.A.4) will serve for all of the KOMP2 activities. The Terms and Conditions described below are specific for this FOA (RFA-RM-10-012), but have been coordinated and made consistent with those described in the other FOAs soliciting components of the KOMP2 Research Network.
The Steering Committee will serve as the main governing board of the KOMP2 Research Network. The Steering Committee membership will include the P.I. of each awarded cooperative agreement and the NIH Project Scientist of each of the components of the KOMP2 Research Network. Additional members may be added by action of the Steering Committee. Members of the KOMP2 Working Group may attend the Steering Committee meetings. Government employees outside of KOMP2 Working Group members may also attend, if their expertise is required for specific discussions.
The Steering Committee will:
Each full member will have one vote; the total votes of the NIH Project Scientist-members of the Steering Committee will constitute a minority of the votes. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
Panel of Scientific Consultants:
This program will be coordinated with and be a member of the IMPC. Because that program is in its formative stage, the degree of interactions of the KOMP2 Steering committee with the IMPC and the nature of IMPC input into the oversight of the KOMP2 is not yet known. The advisory structure may include:
A Panel of Scientific Consultants (PSC) will be responsible for reviewing and evaluating the progress of the members of the KOMP2 Research Network toward meeting their individual and collective goals. The PSC will provide recommendations to the KOMP2 Working Group, the Directors of NHGRI, NCRR, and DPCPSI as well as the Directors of the all other participating institutes, about continued support of the components of the KOMP2 Research Network. The Panel will be composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the KOMP2 Research Network. The Panel of Scientific Consultants will be appointed by the Directors of NHGRI, NCRR, and DPCPSI with concurrence from the Directors of all other participating Institutes. The membership of the Panel of Scientific Consultants may be enlarged permanently, or on an ad hoc basis, as needed.
The Panel of Scientific Consultants will meet at least once a year and by conference call 2 to 3 times per year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the PSC members to interact directly with the awardees. Annually, the PSC will make recommendations to the NIH regarding progress of the KOMP2 Research Network and present advice about changes, if any, which may be necessary in the KOMP2 Research Network program to the Directors of NHGRI, NCRR and DPCPSI and the Directors of the other participating institutes.
The KOMP2 Working Group consists of program staff from the each of the NIH institutes supporting the KOMP2. The purpose of the KOMP2 Working Group will be to disseminate information about the progress of the KOMP2 Research Network to the participating institutes and to provide a forum for the participating institutes to discuss issues related to KOMP2. The KOMP2 Working Group members will report to the Director of their respective IC. The KOMP2 Working Group will be chaired by the NHGRI Project Scientist for the knockout mouse phenotyping component of the KOMP2.
2.A.4. Dispute Resolution Process
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter 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 regulations 45 CFR Part 16.
Awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement
Each awardee will be asked
to define a set of monthly milestones at the time of the award and to update
these milestones annually at the anniversary date. These will be made a
condition of the award. In accord with the procedures described above, NHGRI
may withhold or reduce funds for a project that substantially fails to meet its
milestones or to maintain the state of the art in the field.
A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research, peer review, and financial or grants
1. Scientific/Research Contacts:
Colin Fletcher, Ph.D.
Division of Extramural Research
National Institute of Human Genome Research
5635 Fisher Lane
Bethesda, MD 20892
Telephone: (301) 496-7531
FAX: (301) 480-2770
2. Peer Review Contacts:
Ken Nakamura, Ph.D
Office of Scientific Review
National Human Genome Research Institute
5635 Fishers Lane
Bethesda MD 20892
Telephone: (301) 496-7531
3. Financial or Grants Management Contacts:
Grants Management Officer
Grants Administration Branch
5635 Fisher Lane
Bethesda, MD 20892
Telephone: (301) 496-7531
FAX: (301) 402-1951
Required Federal Citations
Use of Animals in Research:
Recipients of PHS support for activities involving live, vertebrate animals must comply with PHS Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/PHSPolicyLabAnimals.pdf) as mandated by the Health Research Extension Act of 1985 (http://grants.nih.gov/grants/olaw/references/hrea1985.htm), and the USDA Animal Welfare Regulations (http://www.nal.usda.gov/awic/legislat/usdaleg1.htm) as applicable.
Human Subjects Protection:
Federal regulations (45CFR46) require that applications and proposals involving human subjects must be evaluated with reference to the risks to the subjects, the adequacy of protection against these risks, the potential benefits of the research to the subjects and others, and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).
Data and Safety Monitoring Plan:
Data and safety monitoring is required for all types of clinical trials, including physiologic toxicity and dose-finding studies (phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative trials (Phase III). Monitoring should be commensurate with risk. The establishment of data and safety monitoring boards (DSMBs) is required for multi-site clinical trials involving interventions that entail potential risks to the participants (NIH Policy for Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).
Sharing Research Data:
Investigators submitting an NIH application seeking $500,000 or more in direct costs in any single year are expected to include a plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).
Investigators should seek guidance from their institutions, on issues related to institutional policies and local IRB rules, as well as local, State and Federal laws and regulations, including the Privacy Rule.
Genome-Wide Association Studies (GWAS):
NIH is interested in advancing genome-wide association studies (GWAS) to identify common genetic factors that influence health and disease through a centralized GWAS data repository. For the purposes of this policy, a genome-wide association study is defined as any study of genetic variation across the entire human genome that is designed to identify genetic associations with observable traits (such as blood pressure or weight), or the presence or absence of a disease or condition. All applications, regardless of the amount requested, proposing a genome-wide association study are expected to provide a plan for submission of GWAS data to the NIH-designated GWAS data repository, or provide an appropriate explanation why submission to the repository is not possible. Data repository management (submission and access) is governed by the Policy for Sharing of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/
Access to Research Data through the Freedom of Information
The Office of Management and Budget (OMB) Circular A-110 has been revised to provide 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 funding opportunity 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.
Sharing of Model Organisms:
NIH is committed to support efforts that encourage sharing of important research resources including the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of grantees and contractors to elect and retain title to subject inventions developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or contract proposal, beginning with the October 1, 2004 receipt date, are expected to include in the application/proposal a description of a specific plan for sharing and distributing unique model organism research resources generated using NIH funding or state why such sharing is restricted or not possible. This will permit other researchers to benefit from the resources developed with public funding. The inclusion of a model organism sharing plan is not subject to a cost threshold in any year and is expected to be included in all applications where the development of model organisms is anticipated.
Inclusion of Women And Minorities in Clinical Research:
It is the policy of the NIH that women and members of minority groups and their sub-populations must be included in all NIH-supported clinical research projects unless a clear and compelling justification is provided indicating that inclusion is inappropriate with respect to the health of the subjects or the purpose of the research. This policy results from the NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH definition of clinical research; updated racial and ethnic categories in compliance with the new OMB standards; clarification of language governing NIH-defined Phase III clinical trials consistent with the new PHS Form 398; and updated roles and responsibilities of NIH staff and the extramural community. The policy continues to require for all NIH-defined Phase III clinical trials that: a) all applications or proposals and/or protocols must provide a description of plans to conduct analyses, as appropriate, to address differences by sex/gender and/or racial/ethnic groups, including subgroups if applicable; and b) investigators must report annual accrual and progress in conducting analyses, as appropriate, by sex/gender and/or racial/ethnic group differences.
Inclusion of Children as Participants in Clinical Research:
The NIH maintains a policy that children (i.e., individuals under the age of 21) must be included in all clinical research, conducted or supported by the NIH, unless there are scientific and ethical reasons not to include them.
All investigators proposing research involving human subjects should read the "NIH Policy and Guidelines" on the inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).
Required Education on the Protection of Human Subject Participants:
NIH policy requires education on the protection of human subject participants for all investigators submitting NIH applications for research involving human subjects and individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.
Human Embryonic Stem Cells (hESC):
Criteria for federal funding of research on hESCs can be found at http://stemcells.nih.gov/index.asp and at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-09-116.html. Only research using hESC lines that are registered in the NIH Human Embryonic Stem Cell Registry will be eligible for Federal funding (http://escr.nih.gov). It is the responsibility of the applicant to provide in the project description and elsewhere in the application as appropriate, the official NIH identifier(s) for the hESC line(s) to be used in the proposed research.
NIH Public Access Policy
In accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html) investigators must submit or have submitted for them their final, peer-reviewed manuscripts that arise from NIH funds and are accepted for publication as of April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be made publicly available no later than 12 months after publication. As of May 27, 2008, investigators must include the PubMed Central reference number when citing an article in NIH applications, proposals, and progress reports that fall under the policy, and was authored or co-authored by the investigator or arose from the investigator’s NIH award. For more information, see the Public Access webpage at http://publicaccess.nih.gov/.
Standards for Privacy of Individually Identifiable Health
The Department of Health and Human Services (DHHS) issued final modification to the "Standards for Privacy of Individually Identifiable Health Information", the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal regulation under the Health Insurance Portability and Accountability Act (HIPAA) of 1996 that governs the protection of individually identifiable health information, and is administered and enforced by the DHHS Office for Civil Rights (OCR).
Decisions about applicability and implementation of the Privacy Rule reside with the researcher and his/her institution. The OCR website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a complete Regulation Text and a set of decision tools on "Am I a covered entity?" Information on the impact of the HIPAA Privacy Rule on NIH processes involving the review, funding, and progress monitoring of grants, cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.
URLs in NIH Grant Applications or Appendices:
All applications and proposals for NIH funding must be self-contained within specified page limitations. For publications listed in the appendix and/or Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide any other information necessary for the review because reviewers are under no obligation to view the Internet sites. Furthermore, we caution reviewers that their anonymity may be compromised when they directly access an Internet site.
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 FOA is related to one or more of the priority areas. Potential applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.
Authority and Regulations:
This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the intergovernmental review requirements of Executive Order 12372. Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and 45 CFR Parts 74 and 92. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement can be found at http://grants.nih.gov/grants/policy/policy.htm.
The PHS strongly encourages all grant recipients to provide a smoke-free workplace and discourage the 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.
Loan Repayment Programs:
NIH encourages applications for educational loan repayment from qualified health professionals who have made a commitment to pursue a research career involving clinical, pediatric, contraception, infertility, and health disparities related areas. The LRP is an important component of NIH's efforts to recruit and retain the next generation of researchers by providing the means for developing a research career unfettered by the burden of student loan debt. Note that an NIH grant is not required for eligibility and concurrent career award and LRP applications are encouraged. The periods of career award and LRP award may overlap providing the LRP recipient with the required commitment of time and effort, as LRP awardees must commit at least 50% of their time (at least 20 hours per week based on a 40 hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov.
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