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 of Diabetes and Digestive and Kidney Diseases (NIDDK) (http://www.niddk.nih.gov) on behalf of the NIH.
Molecular Transducers of Physical Activity Metabolomics and Proteomics Chemical Analysis Sites (U24)
U24 Resource-Related Research Projects – Cooperative Agreements
U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-012, U24 Resource-Related Research Projects--Cooperative Agreements
RFA-RM-15-013, U01 Research Project--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 Metabolomics and Proteomics Chemical Analysis Sites to join the Molecular Transducers of Physical Activity Consortium (MoTrPAC; http://commonfund.nih.gov/MolecularTransducers). Awards made through this FOA will support the establishment of sites that will use appropriate technology to conduct metabolomics and proteomics analysis of tissues collected from human participants and animals undergoing a physical activity intervention, contribute that data to a public consortium database, and participate in the initial statistical analysis to generate fingerprints of candidate molecular transducers 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 Metabolomics and Proteomics Chemical Analysis Sites of the Molecular Transducers of Physical Activity 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. Awards made through this FOA will support the establishment of sites that will use appropriate technology to conduct metabolomics or proteomics analysis of tissues collected from human participants and animals undergoing a physical activity intervention, contribute that data to a public consortium database, and participate in the initial statistical analysis to generate fingerprints of candidate molecular transducers of physical activity.
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.
NIH plans to fund two to four sites with expertise in metabolomics and/or proteomics, for the discovery of a broad range of molecular transducers (the ‘molecular map’) that underlie the effects of physical activity in humans. One to two similar sites with expertise in nucleic acid sequencing and other technologies necessary for transcriptomics, genomics, and epigenomics will be awarded via a separate FOA (RFA-RM-015-010). All awarded Chemical Analysis Sites will work together to provide a comprehensive molecular analysis of human and animal tissue samples to describe the molecular signals and changes that transduce the benefits of physical activity.
Although the clinical study protocol is not yet known, it can be assumed for planning purposes that approximately 3000 healthy participants of both sexes, all ages including children, races and ethnicities, with a variety of BMI and fitness levels will be enrolled. Participants will be thoroughly characterized physiologically and metabolically, and full genome sequencing will be done on all human participants. They will be exposed to acute physical activity (either resistance or endurance exercise) and blood and skeletal muscle or adipose tissues will be sampled before and at several times afterward to describe the time course of molecular changes in response to physical activity. A subset of the participants will undergo approximately twelve weeks of exercise training, after which they will be characterized using the same battery of tests used at baseline. They will be subjected to another acute bout of physical activity with blood and tissue samples taken before and at several times afterward, to monitor the changes in response to physical activity due to chronic exposure. Although the number of tissue samples has not yet been determined, for the purposes of planning an application it can be assumed that there will be approximately 5000 acute exercise bouts with 5 blood samples and 2-3 tissue samples each, resulting in about 25,000 human blood samples, 7500 skeletal muscle (200mg each), and 7500 adipose tissues (1g each). Half of these will be in response to endurance physical activity, half in response to resistance physical activity. In parallel, animal studies will be conducted in an appropriate model of physical activity, such as rats, that best mimics the human study, and additional tissues that cannot be obtained from people will be harvested, leading to 5,000 to 10,000 samples of tissues such as blood, muscle, heart, brain, kidney, liver, and white and brown fat.
The overall goal of the study is to identify and characterize to the extent possible the molecules that are likely to transmit the healthful benefits of physical activity, and arise in response to acute and chronic physical activity. These molecular transducers will be correlated with the age, body composition, sex, race/ethnicity, fitness level measured by several indices, and changes due to chronic exposure to physical activity. Molecular changes occurring in skeletal muscle in response to endurance and resistance exercise have been quite well described, and several peptide and small molecule myokines and other cytokines have been discovered that communicate from exercising tissues to non-exercising tissues. A recent study showed that some of the benefits of exercise could be conferred to sedentary rodents by transplanting subcutaneous white adipose tissue from chronically exercised rodents. Therefore, an important focus should likely be on identifying all potential circulating signals in blood, and their originating and target tissues and putative pathways.
Several types of targeted and untargeted metabolomics will be important for the analysis of plasma. Circulating signals could be lipids, modified amino acids or other small molecules, and peptides. Discovery and identification of novel signaling molecules should be a priority. Targeted plasma proteomics may also be informative. Exosomes, which are small secreted vesicles, contain mRNA, miRNA, proteins and small molecules and can be targeted specifically from one tissue to another. Protein (and metabolite) analysis of exosomes may therefore be valuable. A strength of the MoTrPAC project is that circulating molecules that arise after physical activity and have the potential to alter transcriptional or translational programs in target tissues can then be compared to such changes described in the potential target tissues. The time courses of these molecules in blood may be highly informative.
The analysis of non-blood tissues should focus on finding signal molecules that are manufactured and/or secreted in response to physical activity, and changes in the tissues themselves that are likely to occur directly in response to physical activity or to signals arising from other tissues. These changes are likely to include lipids and other small molecules, and many classes of peptides and proteins. In addition to global proteomics analysis, a set of modified proteins should be measured, and while phosphorylated and acetylated proteins (especially histones and mitochondrial proteins) are extremely important, other modifications, such as those in response to redox state (disulfide bonds, nitrosylation, sulfenylation) may also be very informative. The time course of changes in post-translational modifications could be monitored. Different tissues may require a tailored set of analyses; for instance, the effects of chronic physical activity on skeletal muscle proteins and mitochondria have been fairly well described, but a similar description of adipose tissue is far less complete but likely to be extremely informative. Likewise, adipose tissue may produce and excrete a different set of adipokines before and after physical activity, or after exercise training, and a comparison of those molecules found in adipose tissue with circulating molecules will be informative. Applicants should describe the highest priorities for metabolic and proteomic tissue analyses. Profiles of these molecules should be related to reference data when possible and strategies should be described for analysis in relation to other extant or developing data resources.
Genomics, Epigenomics, and Transcriptomics Sites awarded through RFA-RM-015-010 will synergize with the Proteomics and Metabolomics Sites funded through this FOA. For example, they will use their expertise to conduct whole genome sequencing on all human participants. They will perform transcriptomic analysis to monitor coding and non-coding RNAs in plasma and solid tissues. These Sites will also measure epigenomic changes such as DNA methylation and histone binding in human skeletal muscle and adipose tissue, and other tissues from animal models. These studies will complement the histone modification analyses done at the Proteomics and Metabolomics Sites.
Given the extensive scope of signals and molecular changes expected to occur in response to physical activity, the many powerful technologies that can be brought to bear for analysis, and the broadly inclusive nature of the expected clinical study, Chemical Analysis Site investigators will need to prioritize and strategize to obtain a reasonably thorough integrated analysis across the human participants and animal tissues, using the available funds. Applications should therefore propose a strategy to best analyze tissues to discover as many of the molecular transducers that arise over time following acute physical activity as possible, and to characterize them across a wide range of age, sex, body composition, race/ethnicity, fitness, and exposure to chronic physical activity. Applicants should justify the choice of analyses with reference to technical and scientific validity and cost-effectiveness. A final overall analysis plan will be devised by the Steering Committee in the first year of the project. Awarded sites will work together to provide the approved range of analyses. Molecule identification will likely be the key to a complete molecular description of the response to physical activity, and Chemical Analysis Sites should propose a strategy for identification of novel signals likely to be important. To facilitate timely sharing and analysis of data, Chemical Analysis Sites will assess the data quality and identify important fingerprints of molecules that respond to physical activity, and work closely with the Bioinformatics Center to deposit data quickly so that other Consortium members can access it and can apply appropriate secondary data analysis techniques such as gene network and pathway analyses.
Applicants may want to propose limited pilot projects of some analytical approaches/platforms on a small sample of tissues early in the project, such as specific types of protein modifications or specialized exosome analysis. These may then be expanded into a larger set of tissues if proven to be informative. Applicants may also propose well justified pilot studies to analyze samples that are not currently planned for collection, such as urine. These will be considered by the Steering Committee during the planning stage of the project.
Metabolomics and Proteomics Chemical Analysis Sites will be expected to:
Nucleic acid sequencing will be performed at additional chemical analysis sites which are invited via RFA-RM-015-010. Therefore, applications with such technologies will not be considered responsive to this FOA.
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 per year 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 an estimate of 2-4 awards in FY2016. The amount of funds available for these awards is $150,000 for FY2016, and a total of approximately $54,500,000 for fiscal years 2017-2021. Actual amounts will depend on annual appropriations.
Application budgets are limited to $50,000 direct costs in the first year, $2,000,000 direct costs in year 2, $4,500,000 direct costs in each of years 3 through 5, and $3,500,000 direct costs in year 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.
Facilities & Other Resources. Provide detailed information regarding the resources--such as laboratory equipment, instrumentation, computers and software--available to the applicant, either in the applicant lab or in a core facility. Define the proposed Site’s capabilities relative to the current state-of-the-art of the field. Provide sufficient detail to allow reviewers to judge the contributions and interrelationships of relevant ongoing research. Briefly describe any additional features of the institutional environment that will contribute to the success of the MoTrPAC.
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. Applicants are encouraged to include, in their team, expertise in physical activity research so that the application best captures the kinds of analyses likely to be valuable to describe the molecular map of physical activity;
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 sample analysis only. This should include minimal personnel costs and travel to three Steering Committee Meetings.
The budgets for year 2 and following years will include costs incurred for analysis of human and animal tissues. These include personnel, supplies, sample preparation and analysis, quality control and appropriate bioinformatics, and any costs associated with data transfer to the CCC. Budgets for the second year and after of the award may be adjusted after the study has been completely planned in year 1. It is not the purpose of this FOA to support the purchase of instrumentation, which will not be allowed unless there is compelling justification.
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 analyzing tissues collected in MoTrPAC Clinical Centers and PASS using metabolomics and proteomics technologies. Describe each specific goal and the role of the applicant Chemical Analysis Site in achieving the overall objectives of the MoTrPAC.
Tissue Analysis Plan: Each application should include a tissue analysis plan which outlines the type and number of human and animal tissues to be analyzed by each proposed technology, along with the amount of tissue needed. It is unlikely that all desired analyses can be done on all tissue samples. Therefore, the plan should indicate which analyses should be done on all or most samples, and which should be done on a subset. Each element of this plan should be justified in terms of cost and scientific contribution to the overall goals of the MoTrPAC. It is permissible to suggest that some analyses be piloted on a small number of samples early in the course of the project; in that event, criteria should be provided for deciding to scale up those analyses to larger numbers of tissues.
Project Structure: It is anticipated that at a minimum the Chemical Analysis Site will have an Administrative, a Bioinformatics, and one or more Chemical Analysis elements.
Administrative Element: This element will be led by the PD/PI and be responsible for the overall management of the work done by the Chemical Analysis Site and for coordination with the CCC and other MoTrPAC sites. It will work closely with the Chemical Analysis Element to ensure receipt, preparation and analysis of the various tissue specimens collected at the Clinical Centers and PASS. The PD/PI will likely be assisted by a program coordinator who will oversee day-to-day operations and manage budgets, travel, communication with the Consortium, etc.
The description should include the following:
Bioinformatics Element: The Bioinformatics Element will include expertise to assist in standardization, organization, curation and feature assignment, and initial analysis of the data arising from the Chemical Analysis Element(s). Bioinformatics staff will likely work closely with similar staff in the other Chemical Analysis Sites as well as the Bioinformatics Center to assemble, integrate, and analyze data.
The description should include the following:
Chemical Analysis Element(s): Each Site will have one or more Chemical Analysis Elements in which tissue samples will be analyzed. The staff will be expert and experienced in one or more high-throughput discovery chemical analysis approaches. Staff will assist the PD/PI and inform the planning process regarding the development of standard operating procedures for sample collection, processing, choice of analyses, etc. They will be able to provide high quality, reproducible analysis of tissue samples collected at the Clinical Centers and PASS.
The description should include the following:
Preliminary Data: Preliminary data should indicate that the expertise of the staff and the resources available in terms of equipment and infrastructure are appropriate for the project. Preliminary data should indicate the feasibility of proposed assays, as well as the quality, reliability, and reproducibility of resulting data. Applicants should indicate an ability to handle large sets of tissue specimens for the proposed analysis. In addition, data can be presented to illustrate proposed bioinformatics strategies for identifying important molecular fingerprints and strategies for identification of novel signals in those fingerprints.
It is appropriate to provide evidence that the site can function well in a consortium, adhere to agreed-upon common protocols, receive tissues, produce and transmit data in an accurate and timely fashion, and operate within the proposed organizational structure.
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. Describe an approximate timeline for the proposed analyses, along with milestones. These should address at a minimum the time to full production, throughput at full production, and time from tissue receipt to data deposition at full production.
Letters of Support: Institutional commitments made to the Chemical Analysis Site 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 of Diabetes and Digestive and Kidney Diseases (NIDDK), 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.
Important Update: See NOT-OD-16-006 for updated review language for applications for due dates on or after January 25, 2016.
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 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 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?
Is there a sound rationale for the selection of cutting edge technologies? Is there evidence of technical excellence and capacity for the proposed analytics, demonstrating general feasibility of the proposed approaches? Are proposed tests efficient in terms of cost and tissue sample use? Is the projected capacity and throughput of the site adequate? Are there plans for standardization and validation? Are procedures in place to ensure quality of data and consistency of the experimental techniques as well as adequate data management and statistical plans for the proposed analyses?
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 work with other awarded Chemical Analysis Sites to carry out analyses on human and animal tissues as planned by the Steering Committee? 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 Diabetes and Digestive and Kidney Diseases Advisory Council. 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: https://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
GrantsInfo (Questions regarding application
instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Padma Maruvada, Ph.D.
National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
Richard Ingraham, Ph.D.
Scientific Review Officer (CSR)
Ms. Sharon Bourque
National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK)
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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