National Institutes of Health (NIH)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (Common Fund) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). The FOA will be administered by the National Institute on Aging (NIA) (http://www.nia.nih.gov) on behalf of the NIH.
Molecular Transducers of Physical Activity Preclinical Animal Study Sites (U01)
U01 Research Project – Cooperative Agreements
U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-011, U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-012, U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-014, U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-015, U01 Research Project--Cooperative Agreements
The purpose of this FOA is to invite applications for Preclinical Animal Study Sites (PASS) to join the Molecular Transducers of Physical Activity Consortium (MoTrPAC; http://commonfund.nih.gov/MolecularTransducers). Awards made through this FOA will support the collection of tissue samples from one species of exercised animals that complement the data and tissue collection in the human clinical protocol, as well as conduct initial detailed mechanistic studies to explore the functions, sources, and target tissues of molecules that transduce the effects of physical activity.
Six companion FOAs will establish the elements of the MoTrPAC. Clinical Centers will collect tissues such as blood, muscle, and fat from well-characterized participants engaging in physical activity. Biospecimens will be analyzed by Genomics, Epigenomics, and Transcriptomics Chemical Analysis Sites and Metabolomics and Proteomics Chemical Analysis Sites. Preclinical Animal Studies Sites (PASS) will provide additional tissues that cannot be obtained from human subjects and allow for further characterization and validation of molecular transducers identified from the chemical analysis of human samples. A Bioinformatics Center will oversee data standardization, integration, and storage and will implement data sharing and computational tools for the integrated analysis of clinical and molecular data. Overall coordination will be provided by a Consortium Coordination Center (CCC).
Awardees will comprise the MoTrPAC and must work collaboratively to plan and execute a large study to discover and characterize the molecular transducers (the 'molecular map') that underlie the beneficial effects of physical activity in humans. The product will be a publically available data resource that will enhance and accelerate subsequent mechanistic research on diseases and conditions affected by physical activity.
October 8, 2015
February 18, 2016
February 18, 2016
March 18, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date. No late applications will be accepted for this Funding Opportunity Announcement.
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
March 19, 2016
Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.
The purpose of this FOA is to invite applications for the Preclinical Animal Study Sites (PASS) as part of the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) (http://commonfund.nih.gov/MolecularTransducers). The MoTrPAC is a national research consortium designed to discover and perform preliminary characterization of the range of molecular transducers (the ‘molecular map’) that underlie the effects of physical activity in humans. PASS studies will be divided into two phases. Successful applicants will contribute to the effort by participating in all of the following Phase 1 and Phase 2 activities.
In Phase 1, the PASS will:
In Phase 2, the PASS will:
The goal of the Molecular Transducers of Physical Activity in Humans Consortium (MoTrPAC) is to assemble a comprehensive map of the molecular changes that occur in response to physical activity and, when possible, relate these changes to the benefits of physical activity. This map will contain the many molecular signals that transmit the health effects of physical activity, and indicate how they are altered by variables such as age, sex, body composition, fitness level, and chronic exposure to exercise. Information will be housed in a user-friendly public data resource that any researcher can access to develop hypotheses regarding the molecular mechanisms through which physical activity can improve or preserve health.
Lack of physical activity is at the root of numerous common chronic health problems plaguing many individuals around the world. Despite this, we have a poor understanding of the actual molecular mechanisms by which the benefits of physical activity are realized. Molecular signals produced by physical activity are likely to be numerous and diverse, with impacts on many target tissues. The development of a ‘molecular map’ of circulating signals produced by physical activity and the molecular changes that result in target tissues is a daunting task. Yet, it is now possible because of recent advances in several powerful high-throughput discovery approaches, including metabolomics, proteomics, genomics, transcriptomics, and epigenomics.
The MoTrPAC will be funded via cooperative agreements as a consortium, through six interrelated FOAs. Clinical Centers (RFA-RM-15-015) are central to the overall success of the project. The clinical cohort will consist of healthy males and females of all ages and of different races/ethnicities; some volunteers will be highly active at the beginning of the study, while others will have sedentary lifestyles. Investigators will characterize all participants at baseline with respect to age, sex, and objective physiologic, morphometric, and metabolic fitness measures, as well as collect biospecimens (e.g., blood; skeletal muscle and subcutaneous adipose tissue) before and at several times after a single episode of endurance or resistance exercise. Sedentary participants will participate in a multi-week endurance or resistance training program, after which the investigators will again assess appropriate objective physiologic, morphometric, and metabolic fitness measures before and sample blood and tissues before and after an acute bout of exercise. Samples will be extensively analyzed using high-throughput technologies that allow rapid identification of many different biological molecules from large numbers of samples. This service will be provided by the Metabolomics and Proteomics Chemical Analysis Sites (RFA-RM-15-011) and the Genomics, Epigenomics, and Transcriptomics Chemical Analysis Sites (RFA-RM-15-010). Thorough analysis will enable characterization of a variety of molecules that are altered following physical activity and may thereby contribute to mediating the effects of physical activity. Additional awards will allow Preclinical Animal Study Sites (PASS, RFA-RM-15-013) to conduct experiments in animals that will provide tissues to the Chemical Analysis Sites for the identification of molecular transducers induced by physical activity in tissues that cannot be obtained from humans (e.g., lung, liver, brain, and heart), as well as conduct studies focused on preliminary characterization of novel transducers. Molecular data from the Chemical Analysis Sites and physiologic, morphometric, and metabolic data from the Clinical Centers and PASS will be integrated, stored, and shared by the Bioinformatics Center (RFA-RM-15-012). A Consortium Coordinating Center (CCC, RFA-RM-15-014) will coordinate the entire project including PD/PI meeting organization, training, biospecimen storage and shipping, and workshops. A Steering Committee will design and oversee the entire study to ensure that all aspects of the clinical and animal protocols and the analysis plans will contribute to the mapping of molecular changes that occur in response to physical activity and to prioritize which molecules merit additional characterization by the PASS. An institution can apply to more than one of these FOAs.
Study timeline: The first year will be set aside to assemble the Steering Committee and plan the study, during which time only limited funds will be awarded. It will be followed by five additional funded years during which the study will be implemented. PASS are expected to begin to generate tissues at the end of the first year, and so Chemical Analysis Sites will likely begin to analyze animal plasma and tissues early during the second awarded year, while clinical studies get underway. Molecular data should be continually and sequentially available to Consortium members as it is acquired in order to best inform all aspects of the study. Human tissue samples will be analyzed on a rolling basis as they are made available, which is expected to be late in year 2. Clinical Centers are expected to complete their studies by the end of year 5. Analysis of tissues will continue through year 6, and all data are expected to be deposited in a public data resource by the end of year 6. Molecular fingerprints will be gleaned from the data as they are collected, and it is expected that substantial data analyses will take place in year 6. Staff from all MoTrPAC elements are encouraged to participate in analysis of this highly complex and rich dataset. The Bioinformatics Center personnel will facilitate these data analyses and data dissemination.
Applicants are expected to take full advantage whenever possible of resources such as databases, catalogues, technologies, protocols, and data standards developed through other national and international efforts, particularly NIH Common Fund programs which are described at http://commonfund.nih.gov/. Examples include Big Data to Knowledge (https://commonfund.nih.gov/bd2k/index); Bioinformatics and Computational Biology (https://commonfund.nih.gov/bioinformatics/index); Libraries of Integrated Networks of Cellular Signatures (LINCS) (http://commonfund.nih.gov/LINCS/index); Epigenomics (https://commonfund.nih.gov/epigenomics/index); Extracellular RNA Communication (https://commonfund.nih.gov/Exrna/index); Human Microbiome Project (https://commonfund.nih.gov/hmp/index); Genotype-Tissue Expression (GTEx) (https://commonfund.nih.gov/GTEx/index); and Metabolomics (https://commonfund.nih.gov/metabolomics/index).
Prospective applicants are invited to an informational webinar with NIH staff on 10/22/2015 at 2:00 pm EDT. Details will be posted at http://commonfund.nih.gov/MolecularTransducers.
The purpose of this FOA is to provide support for up to three Preclinical Animal Study Sites (PASS) as part of the MoTrPAC. The first year will be used to assemble the MoTrPAC Steering Committee, plan the clinical and animal study protocols, construct a detailed analytical plan, plan for movement and storage of tissues and data, construct activity and data standards, and begin to prepare for the database and data analysis. In the first phase of the project, these sites will conduct exercise protocols on a single preclinical animal species that parallels the human protocols conducted at the Clinical Sites. The PASS will serve to confirm human data and extend the analyses of candidate transducers of physical activity from the clinical study across multiple organs and tissues that are not accessible from human participants (Phase 1, 1-2 years duration). As noted in the Chemical Analysis Sites FOAs (RFA-RM-15-010 and RFA-RM-15-011), the PASS element of the MoTrPAC is expected to produce between 5,000 and 10,000 samples of various tissues (e.g., blood, muscle, brain, liver, kidney, and adipose tissue) during Phase 1. All tissues harvested will be distributed for analyses according to MoTrPAC protocols. In Phase 2 (3-4 years duration), the PASS will investigate the source and target tissues of candidate signaling molecules that arise in response to acute or chronic resistance and endurance physical activity, and identify the involved pathways and functions; decisions regarding which findings to pursue will be made in consultation with the Steering Committee. Thus, Phase 2 initial mechanistic studies will begin to elucidate molecular cascades likely contributing to the findings of the human studies and identify the target tissues for candidate transducer molecules for the purpose of generating testable hypotheses regarding how the transducers mediate the effects of physical activity on health in humans. Applicants can propose assays designed to identify target tissues using specific cell and animal models. They may suggest assays focused on the functional or molecular changes associated with the beneficial effects of physical activity on specific pathways or systems. They may suggest a focus on finding the function of specific families of molecules altered by physical activity, such as miRNAs, modified lipids or amino acids, or post-translational protein modifications. Awardees selected for this and the companion FOAs will participate as members of the Steering Committee, contributing to the final overall design and coordination of the clinical human and preclinical animal studies.
While the first two years of MoTrPAC PASS activities will only require a small number of investigative teams (2-3 teams) to plan and carry out the animal exercise studies that complement the human study design, the subsequent detailed mechanistic studies to evaluate the data will require additional laboratories. To fill this need, NIH anticipates releasing a second preclinical FOA (pending the availability of funds) to add 5-7 innovative groups to address additional mechanistic questions. The entire cadre of MoTrPAC PASS investigators will collaborate to design and conduct detailed mechanistic studies in preclinical model systems to identify the sources, signaling pathways, physiological targets and functions of the molecular transducers of physical activity found in blood and tissues, recognize feedback and interaction effects among different pathways, and discover the specific roles of the molecules associated with specific health benefits. Awards under the second preclinical FOA are expected to begin in FY 2018 and run through FY 2021.
PASS PD/PIs will be expected to:
The award funded under this FOA will be a cooperative agreement (see Section VI.2.A. Cooperative Agreement Terms and Conditions of Award). Close interactions amongst the awardee, awardees from the companion FOAs, and NIH will be required. Shortly after the award, the PDs/PIs and NIH program staff will form the MoTrPAC Steering Committee. Each funded element will have one vote and the NIH Project Scientist(s) will have one vote. Consortium governance rests with the Steering Committee and is subject to oversight by an NIH MoTrPAC Working Group of the NIH Common Fund.
The NIH will appoint a chair of the Steering Committee from among the MoTrPAC PDs/PIs. The Steering Committee Chair will preside at all Steering Committee meetings and serve on an Executive Committee. The Executive Committee will invite expert consultants as needed, assist as necessary with annual progress reports, and appoint and charge members of subcommittees. These subcommittees will facilitate development, implementation, and monitoring of specific MoTrPAC functions as needed, such as participant phenotyping, study monitoring (protocol adherence, participant safety, etc.), disbursement of tissues among the Chemical Analysis Sites, tissue analysis, data handling, and quality control. Key personnel will be expected to serve on subcommittees as appropriate according to their expertise.
The Steering Committee will meet in person three times during the first year and at least annually thereafter. Monthly teleconferences will be held for the Steering Committee and its subcommittees, and these may be more frequent at times to facilitate planning, etc. The CCC will be responsible for arranging and facilitating the meeting and teleconferences. Applicants should plan to attend an initial planning meeting of the Steering Committee in Bethesda, Maryland, on October 13-14, 2016.
The Steering Committee will have responsibility for developing the overall scientific direction of the program; assuring compliance with program policies and procedures; designing study protocols; implementing studies; ensuring data quality and completeness; planning for analysis and interpretation of data; and reporting results in presentations and publications. The Steering Committee must work cooperatively and interactively during the first year to develop the final protocols and all of the materials necessary to begin the human studies twelve months after award. The final plan, with a study timeline and milestones, will be submitted for consideration by the NIH MoTrPAC Working Group and the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) before the second year of funds will be awarded.
First year planning activities include, but are not limited to:
External Study Monitoring
Five to seven External Scientific Advisors will provide input based on their individual areas of expertise as needed over the course of the program. They will assist the NIH MoTrPAC Working Group regarding processes and substantive issues that arise during the project and will help ensure that the resources to be delivered by the program are as useful as possible for the end users.
An independent DSMB will be established to monitor and provide recommendations to the NIH regarding participant recruitment/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review the Steering Committee-approved common protocol, informed consent templates, milestones, and monitoring plans prior to the start of recruitment. A single central Institutional Review Board (IRB) may be used if it serves to streamline the protocol approval process and to standardize the monitoring of human subjects’ protection in the MoTrPAC.
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
NIH intends to fund 2-3 awards in FY2016. The amount of funds available for these awards is $67,500 for FY2016, and a total of approximately $6,900,000 for fiscal years 2017-2021. Actual amounts will depend on annual appropriations.
Application budgets are limited to $15,000 direct costs for year 1, and to $325,000 direct costs in each of years 2 through 6. Budgets should reflect the actual needs of the proposed project.
Applicants should request a project duration of six years.
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.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization 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 support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
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.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Richard Ingraham, Ph.D.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed. Key personnel should demonstrate strong scientific, administrative, technical, and management expertise in the areas that are critical to the success of the application, including experience with working productively in collaborative environments; and experience with administrative management of resource-based operations that serve the biomedical research community, such as reagent-generating or service-providing consortia or centers.
All instructions in the SF424 (R&R) Application Guide must be followed.
The budget for the first year will be for participation with the Steering Committee, in study planning activities, and preparation for the clinical study only. This should include minimal personnel costs and travel to three Steering Committee Meetings.
Budgets for the second year and after of the award may be adjusted after the study has been completely planned in year 1.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
It is recognized that applicants will NOT know in advance with whom they will be collaborating because the members of the MoTrPAC will not be known before award; therefore applicants should make reasonable assumptions as to the types of collaborations that will be available and build flexibility into their research plans.
Specific Aims: The overall goal is to contribute to the development of a molecular map of transducers that underlie the effects of physical activity in humans by collecting tissue samples from exercised animals to complement the data and tissue collection in the human clinical protocol and conducting mechanistic studies to explore the functions, sources, and target tissues of molecules that transduce the effects of physical activity. Please describe the specific aims for the proposed Preclinical Animal Studies Site and the applicant Site's role in achieving the overall objectives of the MoTrPAC.
Research Strategy: The PASS, in consultation with the Steering Committee, will implement the animal exercise protocols and tissue harvesting, and coordinate shipment to the appropriate Analysis Site. In addition they will conduct the subsequent initial mechanistic studies. Applicants should outline and justify a strategy for how this would best be accomplished, understanding that the actual final details will be agreed to in consultation with the Steering Committee post award. The applicants are also encouraged to identify key design issues and pitfalls that would benefit from broad discussion with the Steering Committee. Applicants should suggest initial exercise designs for animal studies that will parallel a human study (as briefly described above and outlined in RFA-RM-15-015) as closely as possible, with a strong rationale for the design, species, strain, and tissue samples to be harvested (Phase 1 studies) and a cost-effective, informative strategy for analysis of animal tissues at the Chemical Analysis Sites using approaches outlined in RFA-RM-15-010 and RFA-RM-15-011).
Applicants are also expected to suggest potential strategies for selecting molecules to be examined in the initial Phase 2 mechanistic studies. Decisions regarding which molecules and pathways to pursue under this FOA will be made in partnership with the Steering Committee. The extent to which these molecules and pathways occur in the human exercise response will be a key consideration.
Applicants should lay out a clear plan for conducting the analysis of molecules, networks, and cellular processes that are implicated, through analysis of the data obtained from humans and Phase 1 of the PASS, as critical signals or transducers of responses to physical activity. More than one strategy for mechanistic assessment may be proposed as part of an overall strategy. These may include elements which focus on genetic analyses, biochemical approaches, high throughput strategies, etc. While traditional cell culture models may be appropriate for these studies, inter-tissue signaling and response should be emphasized, with analysis of function and molecular interactions done in many physiologically relevant tissues. High throughput assays that allow functional analysis of many putative signals and/or many target cell types should be considered. Assays proposed for Phase 2 of the PASS should be capable of analyzing diverse types of molecules, cells, and tissues; applicants should describe their ability to assess function of lipids, miRNAs, other RNAs, peptides, small molecule metabolites, etc. as signals, and their ability to assess responses in diverse cell types. Applicants should propose and justify priorities for analyzing different classes of molecules and tissues. Statistical methods that will determine required sample sizes or that will inform analysis of results should also be fully described.
Phase 1: Provide a concise description of the overall strategy, methodology, and analyses to be used to accomplish the goals and specific aims of the study, which is to provide tissues from an animal model of endurance and resistance physical activity for transcriptomics, epigenetics, metabolomics, and proteomics analysis at the Chemical Analysis Sites. The model organism, exercise protocols, tissues, and the subsequent analyses are expected to complement the human data collected through RFA-RM-15-015.
This should include at a minimum:
Phase 2: Applicants should lay out a clear plan for investigating tissues, molecules, networks, and cellular processes implicated through analysis of the data obtained from humans and Phase 1 of the PASS as critical signals or transducers of responses to physical activity. Prior to sufficient human data being available, initial Phase 2 mechanistic studies should focus on exploratory studies of potential targets and pathways of molecules of known relevance to human physiology. More than one approach for mechanistic assessment may be proposed as part of an overall strategy. Provide a concise description of the overall strategy, methodology, and analyses to be used to accomplish the goals and specific aims of the study, which are to identify the source and target tissues, important pathways, and functions for molecular transducers of physical activity. Phase 2 studies are expected to be of high impact to the field and address essential scientific questions.
This should include at a minimum:
Collaboration: Applicants should acknowledge the PD's/PI's willingness to abide by the responsibilities as described below in "Cooperative Agreement Terms and Conditions of Award."
Preliminary Data: Due to the highly interactive nature of this initiative with other members of the companion FOAs and the reliance on the planning year to get awardees coordinated and aligned in the overall approach, the submitted applications are unlikely to have the degree of specificity normally expected in an NIH application. Investigators are expected to provide data that supports the choice of animal model (including species and strain), physical activity intervention (acute and training regimens; endurance and resistance activities), choice of tissues to be sampled, timing of tissue sampling, etc. for Phase 1 studies. They also should provide data that supports the choice of animal and cell models and general strategies for exploring the source and target tissues and functions of novel molecular transducers or of classes of molecular transducers (e.g., altered peptides or lipids, miRNAs, other small molecules, post-transcriptional modifications of proteins).
Milestones and Timeline: Because this Consortium will require specific achievable goals (e.g., timely recruitment of participants, expected annual throughput), milestones should be proposed by the applicant. Applicants should demonstrate that they can exercise and collect tissues from the number of animals needed for the power calculations described in Phase 1 while adhering to the MoTrPAC timeline. Phase 1 studies are likely to require 1 to 2 years. Phase 2 studies should begin no later than the end of year 3.
Letters of Support: Institutional commitments made to the PASS should be clearly documented.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in the application. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. A dissemination plan guided by the following principles is thought to promote the largest impact:
1. The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
2. The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
3. To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
4. The terms of software availability should include the ability of researchers outside the Center and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the Center. An applicant should take responsibility for creating the original and subsequent “official” versions of a piece of software.
5. Given the long-term goals of this initiative to create software and tools for MoTrPAC research that will serve as a resource to biomedical researchers across the nation, applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the “official” core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.
6. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the National Institute on Aging (NIA), NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
In order to expedite review, applicants are requested to notify the CSR by email at Richard.Ingraham@nih.gov when the application has been submitted. Please include the FOA number and title, PD/PI name, and title of the application.
The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.
Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact 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 review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific 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.
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?
Are the proposed studies likely to enhance the value of the clinical data collected in the MoTrPAC? Are the planned studies of potential physical activity transducers addressing essential scientific questions
Are the PD(s)/PI(s), 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?
Does the site have a sufficient breadth of expertise in preclinical exercise modeling and all proposed experimental approaches to address the full range of needs for the Phase 1 and Phase 2 preclinical animal studies?
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?
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?
Does the application outline a clear rationale for the preliminary design, the species, strain, and tissue samples to be collected, and timing of sample collections? Are the decisions based on a thorough review of the literature and the applicant's own data? Does the application describe key design issues that would benefit from broad discussion with the Steering Committee? Have the applicants demonstrated their ability to complete each phase in a timely manner? Have applicants proposed milestones that indicate a clear path to successfully completing the proposed studies?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
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?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Have the investigators stated their willingness to collaborate with NIH scientists and staff, and with investigators and staff from other elements of the MoTrPAC? Have the investigators stated a willingness to participate in planning the study and to use common protocols? Have the investigators stated a willingness to share all data, biospecimens, and protocols in a timely manner with MoTrPAC members during the project period, and with the broader research community after the completion of the MoTrPAC project consistent with achieving the goals of the program?
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. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
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 on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
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.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
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).
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; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan; and 4) Software Sharing Plan.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA. .
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council on Aging. The following will be considered in making funding decisions:
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.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. 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.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
Milestones are goals that are quantifiable for measuring success, and include associated annual or semi-annual quantitative criteria. Final milestones will be designed during the first year in the planning phase. After consideration by the NIH MoTrPAC Working Group, the final set of approved milestones will be specified in the Notice of Award. Progress towards achieving the final set of milestones will be evaluated by NIH program staff on an annual basis. If justified, future year milestones may be revised based on data and information obtained during the previous year. If, based on the progress report, the project does not meet the milestones, funding for the project may be either restricted or discontinued.
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 and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist(s) will have substantial scientific and programmatic involvement during the conduct of this activity through technical assistance, advice, and coordination. However, the role of NIH staff will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus and that NIH staff will be given the opportunity to offer input to this process.
The Project Scientist(s):
Areas of Joint Responsibility include:
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 regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
GrantsInfo (Questions regarding application
instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
John P. Williams, Ph.D.
National Institute on Aging (NIA)
Richard Ingraham, Ph.D.
Scientific Review Officer (CSR)
National Institute of Aging (NIA)
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
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 Part 52 and 45 CFR Part 75.
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