Office of Strategic Coordination (Common Fund)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (https://commonfund.nih.gov/) through the Office of the NIH Director, Office of Strategic Coordination https://dpcpsi.nih.gov/). All NIH Institutes and Centers participate in Common Fund initiatives. The FOA will be administered by the National Heart, Lung, and Blood Institute (NHLBI) (https://www.nhlbi.nih.gov/) on behalf of the NIH.
Reissue of RFA-RM-17-025
August 23, 2019- Clarifying Competing Application Instructions and Notice of Publication of Frequently Asked Questions (FAQs) Regarding Proposed Human Fetal Tissue Research. See Notice NOT-OD-19-137
The purpose of this Funding Opportunity Announcement (FOA) is to solicit transformative technologies that will significantly expand throughput, multiplexing and discrimination of biomolecules in human tissues for comprehensive mapping of individual cells and their context in human tissues. This FOA supports the accelerated proof-of-principle demonstration and validation of promising tools, techniques and systems that can be integrated, scaled and applied to multiple human tissues, particularly for characterizing functional modifications, lipids and the extracellular environment. The initial two-year UG3 phase will support accelerated development and demonstration of feasibility of these emerging, high impact technologies. The subsequent two-year UH3 phase will support validation in human tissues, optimization, scale-up, and generation of data. Funded projects will be expected to work closely as part of the Human BioMolecular Atlas Program to catalyze development of a framework for 3D mapping the human body with high resolution.
December 2, 2019
February 2, 2020
March 3 , 2020
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
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.
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.
Human BioMolecular Atlas Program (HuBMAP)
The vision for the Human BioMolecular Atlas Program (HuBMAP) is to catalyze development of a framework for mapping of the human body at high resolution to transform our understanding of tissue organization and function. This will be achieved by:
HuBMAP is funded through the NIH Common Fund as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. The NIH Common Fund 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 HuBMAP Consortium will scale-up the range of tissues, technologies, data management and its community engagement activities throughout the duration of the program. The five research initiatives that compose the program are:
Understanding how tissue organization influences a cell’s molecular state, interactions, and history is critical for enhancing our understanding of variation in organ function across the lifespan and health-disease continuum. Despite vastly improved imaging and omics technologies and many important foundational discoveries, our understanding of how tissues are organized is restricted to a very limited number of microscopic structures. Better insights into the principles governing organization-function relationship will potentially lead to better understanding of the significance of inter-individual variability, changes across the lifespan, tissue engineering, and the emergence of disease at the biomolecular level. However, integrating imaging and omics analysis to comprehensively profile biomolecular distribution and morphology of tissues in a high throughput manner and placing this information into 3D tissue maps amenable to modelling has yet to be fully realized.
In a June 2016 meeting (https://www.commonfund.nih.gov/sites/default/files/HuBMAP%20Summary%20of%20Planning%20Meeting.docx) organized by the NIH, experts from the research community identified the following scientific priorities necessary to develop these tissue maps: 1) sourcing high quality tissue from multiple human normal organ sites, 2) processing and preserving tissue for multiple imaging and omics assays, 3) quality control, validation and variation in data generation, 4) data coordination across multiple acquisition techniques, 5) annotation, curation and archiving of the data, 6) browsing, visualizing and searching the data, 7) building statistical and analytic techniques and models for nonlinear analysis of highly multidimensional data and 8) community engagement.
Objectives and Scope for the Transformative Technology Development Projects
This Transformative Technology Development (TTD) FOA seeks to establish the next generation of tools, techniques and methods that will be foundational for mapping the human body with high resolution that provide information not available using current technologies and techniques. Successful projects will develop, demonstrate and validate transformative technologies that can generate extensive, quantitative data on biomolecular distribution in tissues to produce comprehensive 3D tissue maps. Applications are expected: (1) to be high impact with thoughtfully managed risk, (2) to use a milestone-driven engineering approach that considers design, testing and evaluation, and (3) to bring together multi-disciplinary teams that will iteratively design technologies that can be rapidly disseminated for wider use by the HuBMAP Consortium. By the end of the UG3 phase, the goal is to have successful proof-of-principle demonstrations of innovative technologies that can more comprehensively map the distribution of biomolecules in mammalian tissues. All technologies are expected to be capable of quantitatively and reproducibly measure the distribution of many biomolecules in the intra-, inter- and extra-cellular spaces of mammalian tissue, independent of what species it came from. By the end of the UH3 phase the goal is to have optimized, scaled, benchmarked and successfully validated technologies that have been used to generate publication-quality data from multiple non-diseased human tissues. The complementary Rapid Technology Integration (RTI) initiatives will support integration of such technologies at this latter stage of development into the Tissue Mapping Centers. Applicants with more established and/or published results demonstrating proof-of-principle in mammalian tissues are strongly encouraged to wait for the re-announcement of the RTI FOA, which is planned for FY2021. For further information about the HuBMAP Consortium, please see: https://commonfund.nih.gov/hubmap.
This FOA is intended to support the accelerated development of novel in situ imaging, spectrometry and sequencing approaches that have the potential to transform 3D human tissue mapping. These technologies must offer tissue mapping capabilities with significantly improved accuracy, resolution, throughput, or efficiency compared to existing methods described in peer-reviewed publications and must be generalizable and comprehensive enough to provide analysis of many biomolecules of interest across all major human tissues. Programmatic priorities will be given to approaches that are distinct but synergistic with those currently used by the consortium and includes novel technologies and methods to characterize the extracellular environment, functional modifications of proteins and RNA, as well as analysis of lipids. This FOA encourages, but is not limited to, technologies that can address the following challenges:
HuBMAP projects will generate high resolution, high content, high-throughput biomolecular data to generate 3D tissue maps of non-diseased human organs and organ systems. For HuBMAP, a high-resolution assay is one that can reliably and reproducibly assign detected biomolecules to individual cells or extracellular compartments of a tissue. A high content approach is one that maximizes identification of tissue features through a combination of biomolecular depth, spatial resolution and multiplexing of complementary, multi-parameter assays. A high throughput pipeline is one that maximizes the bandwidth of data production to result in any or all of the following: 1) accelerated speed of analysis, so that hundreds or thousands of samples can be analyzed simultaneously, 2) greater depth of analysis, so that hundreds or thousands of molecules can be analyzed in a single sample, or 3) enhanced capacity for volume, so that a given set of molecules can be analyzed in all the cells within a larger tissue sample. Approaches that maximize the volume of tissue that will be analyzed while maintaining cellular resolution and high biomolecular content are strongly encouraged. Successful projects may provide new insights into functional states, such as quiescence and senescence; cell-cell interactions, microenvironment and system-wide signaling; chronobiology; and how changes in tissue organization impact function across the lifespan and the health-disease continuum.
Given the focus of HuBMAP on spatial analysis, proposed technologies must be capable of defining location at high resolution, provide comprehensive insight into the distribution of multiple biomolecules, have the potential to be included into the data production pipelines of HuBMAP's Tissue Mapping Centers, and be applied to multiple human tissues. Although the focus of these projects should be on in-situ analysis of tissues, it is expected that unbiased, dissociative techniques can be used to inform development and validation. It is expected that projects that propose initial development using dissociated cells have a timely and robust plan to establish feasibility in mammalian tissues within the UG3 phase. Projects that have not demonstrated successful analysis of cells in situ by the end of the UG3 phase will not progress to the UH3 phase.
Applications addressing the following topics will be deemed non-responsive and will not be reviewed:
Coordination and Collaboration
Successful applicants to this FOA will become members of the larger HuBMAP Consortium composed of investigators who have been funded in response to at least one of HuBMAP FOAs. The purpose of the Consortium is to enable groups to effectively collaborate with each other to maximize the chances of overall success of the program. In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the Consortium to contribute to developing SOPs, data and metadata standards, metrics for data generation, participate in cross-site studies, engage in cross-training, and guide development of data analysis and visualization tools that can be used by the broader scientific community. A Steering Committee (SC) composed of all the funded principal investigators and NIH staff meets regularly to develop and implement Consortium policies and guide overall direction of the Consortium to meet the goals of the program. This Steering Committee is complemented by an Executive Committee and a set of working groups. NIH staff have also recruited outside experts (non-awardees) as External Program Consultants (EPCs) to provide advice directly to NIH.
New TTD projects will be strongly encouraged to work closely with the other projects of the HuBMAP to demonstrate how their technologies can be integrated and scaled for production of multiple tissue maps across the human body. For example, the TTDs are expected to work closely together with the Tissue Mapping Centers (TMCs) to develop consortium-wide best practices for emerging approaches to data generation, carryout cross-site comparisons and test and validate technologies as applied to multiple tissues. They will also work closely with the HIVE to develop data and metadata standards for emerging technologies, to build calibration and validation datasets and engage in cross-site collaborations. It is envisaged that successful TTDs may transition to the Rapid Technology Integration initiative later during the program providing a pipeline for the comprehensive validation and integration of these innovative technologies into the TMCs. All HuBMAP investigators are required to attend the annual HuBMAP investigator meetings, regular teleconferences with Consortium members and NIH Staff for the duration of the funding cycle. A number of Consortium-wide activities will be defined post-award, and it is strongly recommended that TTD projects plan and budget approximately 20% of their resources for collaboration activities as part of their applications. NIH intends that the products of the TTDs be broadly available to establish the foundations for a human body map that other programs and the community could build upon; this includes methods, tools, reagents, biospecimens, datasets, and software. Projects will be expected to abide by Consortium policies (see: https://hubmapconsortium.org/policies/) for rapidly sharing their products within the Consortium and with the external research community. The robustness and reproducibility of experimental results are critical to the success of HuBMAP. In some cases, conducting additional critical experiments will be important for assessing progress. Therefore, NIH Program staff, in consultation with the PD/PI, may modify or add experiments to be conducted during the duration of an award.
Transformative Technology Development Project Structure
This FOA uses the biphasic UG3 / UH3 cooperative agreement mechanism to support the phased development of innovative technologies that have the potential to transform tissue mapping by the HuBMAP Consortium. Initial UG3 cooperative agreement awards for up to 2 years will be granted for demonstrating the proof-of-principle of these technologies for mapping mammalian tissue. Although the focus of the HuBMAP is on non-diseased human tissue, it is recognized that for technology development during the UG3 phase, analyzing tissue from model animal systems as an intermediate step may reduce biospecimen variability and make results more robust. The subsequent UH3 phase will fund awards for up to 2 years for the scaling, optimization and validation of the technologies for mapping human tissues. During the UH3, projects are expected to demonstrate that the performance of the technology can be benchmarked and enhanced, confirm that this performance can be reproduced with non-diseased human tissue, and compare the results with complementary assays.
Because early-stage transformative technology development is an inherently high-risk high-reward process, it is anticipated that there may be significant attrition as projects move through development and validation. Projects that successfully reach the goals of the UG3 phase will be administratively reviewed, with priority projects proceeding to the UH3 phase pending availability of funds. Investigators responding to this FOA must develop a strategy for both UG3 and UH3 phases in this application. Funded UG3 projects will be asked for an updated strategy prior to the UH3 administrative review, although this does not imply funding for the UH3 phase.
As a cooperative agreement and as part of the HuBMAP Consortium, projects should focus on how they meet the goals of the program, how they significantly improve upon the state-of-the-art, how they can be integrated with other technologies, and how they are capable of being scaled to map multiple human tissues in a high-throughput fashion. Applications should include discussion of performance, dynamic range, sensitivity and specificity of their technologies; calibration and control processes; testing, evaluation and improvement; and interoperability and usability. Projects are strongly encouraged to have ambitious goals and annual milestones. Milestones are goals that are quantifiable for measuring success that can be used for go/no-go decision-making for the project and should include quantitative criteria associated with them. Prior to funding an application, NIH program staff will contact the applicant to discuss the proposed milestones and any changes suggested by the review panel or NIH program staff. A final set of milestones will be specified each year in the Notice of Award. Progress towards achievement of the annual milestones and the overall goals will be regularly evaluated by NIH program staff and they may consult as necessary with independent consultants with relevant expertise. If justified, future year milestones may be revised based on data and information obtained during the previous project period. If, based on the progress report, a funded project does not meet the milestones, funding for the project may be discontinued. In addition to milestones, the decision regarding continued funding will also be based on the overall robustness of the entire data package that adequately allows an interpretation of the results (regardless if they have been captured in the milestones), overall progress, program synergy and priorities, competitive landscape, and availability of funds.
Objectives of the UG3 Phase
During the UG3 phase, the NIH is interested in developing and demonstrating proof of principle of the next generation technologies for 3D quantitative mapping of tissue. These technologies must offer capabilities not currently available for tissue analysis with sufficient throughput and cost effectiveness to analyze large tissue neighborhoods in three dimensions from multiple biospecimens. Expected outcomes include but are not limited to:
Transition from UG3 to UH3: An administrative review will be conducted by NIH Program staff to decide whether a project will be considered for transition from the UG3 phase to the UH3 phase. UH3 eligible projects must have a compelling and innovative technology that has the potential to transform data collection for the HuBMAP and have strong results to support validation in human tissues. To be eligible for transition, projects must have met the Objectives of the UG3 Phase listed above and be considered a high programmatic priority for HuBMAP by actively working as part of the Consortium to the overall program goals and offering unique tissue analysis capabilities. Prior to transitioning, NIH Program staff will contact the applicant to discuss proposed updates to the goals and milestones of the UH3 period and they may consult as necessary with independent consultants with relevant expertise.
Objectives of the UH3 Phase
During the UH3 phase, the NIH is interested in scaling-up, optimizing and validating the proposed novel technology for multiplexed, high-throughput mapping of multiple human tissues. These technologies must be generalizable and comprehensive enough to be capable of providing analysis of user-defined biomolecules of interest across all major human tissues. Expected outcomes include but are not limited to:
Technical Assistance Conference Call
All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA and the HuBMAP Program. A Technical Assistance teleconference will be held for potential applicants from 1-2pm Eastern Time on January 13, 2020. NIH staff will be available to answer questions related to this FOA. Dial in information for the call is posted on the HuBMAP website and slides will be made available on the website for those unable to attend. A list of frequently asked questions (FAQs) related to the program is also be posted on the HuBMAP website (see: https://commonfund.nih.gov/HuBMAP/generalfaqs). The information session is open to all prospective applicants, but participation is not a prerequisite to apply.See Section VIII. Other Information for award authorities and regulations.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
NIH intends to fund an estimate of 3-5 awards, corresponding to a total of $1.5 million, for fiscal year 2020. Future year amounts will depend on annual appropriations.
The scope of the proposed project should determine the project period. The proposed project period for the UG3 may not exceed 2 years and the UH3 phase may not exceed 2 years. The total duration of the UG3 and UH3 phases together may not exceed 4 years.
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 eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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.
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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
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:
Pothur Srinivas, Ph.D., MPH
Specific Aims: Separate specific aims should be submitted for both the UG3 and UH3 phases.
Research Strategy: Approach must be divided into two parts corresponding to the UG3 and UH3 phases. The UG3 phase must include plans for: (1) demonstrating that the proposed novel technology can transform our current capabilities for quantitatively mapping the spatial distribution of biomolecules in tissue, (2) demonstrating that the technology is scalable and generally applicable for the generation of high-resolution biomolecular maps of tissue by generating one such map at reasonable cost within a reasonable time period, (3) coordinating with the HIVE on standardized formats for the deposition and storage of data generated as appropriate and consistent with achieving the goals of the program, (4) developing and sharing Standard Operating Procedures, quality control metrics, software, reagents or metadata elements associated with the technology, within the Consortium, and (5) determining the analytic rigor of the proposed technology platform, benchmarking performance and characterizing technical variability. The UH3 phase must include plans for: (1) optimizing and characterizing the technology to rapidly and efficiently generate comprehensive biomolecular maps of multiple non-diseased human tissues not studied in the UG3 phase, (2) generating validation and publication-quality data from this tissue and submitting the data to the HIVE in a standardized format as appropriate and consistent with achieving the goals of the program, and (3) demonstrating that generated data contributes to a significantly enhanced understanding of the role of biomolecular organization in tissue function.
Milestones and Timeline: A timeline (Gantt chart) including milestones is required. Milestones are goals that create go/no-go decision points in the project and must include clear and quantitative objective criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project's continued progress or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. The application must include well-defined milestones: e.g., appropriate objective performance targets, quantitative for go/no go decision points such as an appropriate level of detection and coefficient of variation, or sensitivity and specificity; and timelines for assessing progress in both the UG3 and UH3 phases, including specific milestones for progressing from the UG3 phase to the UH3 phase. Milestones and timelines for each stage must be provided in a separate heading at the end of the Approach section for each UG3 and UH3 subsection, and should:
The following modifications also apply:
If you answered “Yes” to the question “Are Human Subjects Involved?” on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.Delayed Onset Study
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. 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. When a submission date falls on a weekend or Federal holiday , the application deadline is automatically extended to the next business day.
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 and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
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 How to Apply – Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
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 components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applications Involving the NIH Intramural Research Program
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 Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/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.
Use of Common Data Elements in NIH-funded Research
Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a “Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.
For this particular announcement, note the following:
The UG3/UH3 Phase Innovation Awards Cooperative Agreement supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. Accordingly, reviewers will focus their evaluation on the development, integration, validation and dissemination of tools and techniques that significantly expand throughput, multiplexing and discrimination of biomolecules in human tissues with high resolution to further identify cell types and tissue organization conceptual framework and the potential to significantly advance our knowledge or understanding. An UG3/UH3 grant application need not have preliminary data, extensive background material or a track record of the team working together. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Accordingly, reviewers will emphasize the conceptual framework, the level of innovation, and the potential to significantly advance the goals of the HuBMAP. Reviewers will assign a single impact score for the entire application, which includes both the UG3 and UH3 phases.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? 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?
What qualitative and quantitative contributions will this project make towards the overall goals and objectives of the Human BioMolecular Atlas Program? How will this project transform 3D human tissue mapping by quantitatively mapping the distribution of biomolecules? Is it likely that the proposed technology will significantly expand throughput, multiplexing and discrimination of biomolecules in human tissues with high resolution? How easily can the technology be applied to comprehensively assess the intra-, inter- and extra-cellular organization of multiple human tissues? To what extent will the technology, data and knowledge generated by this project lead to a better understanding of the relationship between tissue organization and function?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or those 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?
What experiences/attributes do team members bring that engender confidence they are appropriate and sufficiently diverse to effectively manage a high-risk, milestone-driven project to develop and validate a new technology? How strong is the team regarding expertise in design, development, testing and validation of their proposed technology? To what extent will the proposed leadership plan and commitment of time enhance the likelihood of success? Does the team have expertise in developing and validating new technologies as part of a consortium? What is the likelihood that all the collaborators and partners will work together effectively to meet the timeline to complete the milestones proposed for the transition from UG3 to UH3?
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?
How and to what extent will the proposed technology facilitate a paradigm shift, transforming 3D human tissue mapping in a way not possible by existing technologies? How is the design of the project creative, innovative, relevant to HuBMAP's goals, and what evidence suggests it will accelerate development in a way that would not obviously happen otherwise?
Does the project have an optimal balance in proposing a high-risk technology which has not yet been benchmarked or validated in mammalian tissue, while also having a thoughtful risk-mitigation strategy to develop the technology in such a way that other researchers will want to use it and have confidence in the results?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project ? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? 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? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
How has the project proposed a rigorous approach to development that will result in a robust, calibrated, benchmarked and cross-validated technology? Does the approach include sufficient studies to understand the analytic rigor and biologic validity of the proposed technology? Are appropriate metrics identified for assessing project progress, benchmark technology performance and that will discriminate technical artifacts from biological signal?
Are the proposed timeline and milestones for the UG3 phase likely to result in successful proof-of-principle demonstration of the technology for quantitatively map the distribution of biomolecules in mammalian tissue? How likely will the proposed timeline and milestones for the UH3 phase result in a technology that has been optimized, scaled, benchmarked and validated for high-throughput mapping of non-diseased human tissue?
How and to what extent does the project propose to collaborate and coordinate with the other HuBMAP initiatives to share resources and details of the technology, consistent with the goals of the program, and will this result in successful upload of data to the HIVE and demand to use the technology by the Tissue Mapping Centers?
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 individuals of all ages (including children and older adults), 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?
Are the resources, equipment and infrastructure available and in place (or readily obtainable) to achieve the goals of the UG3 within 2 years?
Are the instrumentation and data science resources in place (or readily obtainable) and adequate to support the project and interactions with the rest of the HuBMAP Consortium?
For research that involves human subjects but does not involve one of the 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 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 individuals of all ages (including children and older adults) 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 criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. 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.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
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 (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
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 the Center for Scientific Review, 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:
Applications will be assigned on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
Information regarding the disposition of applications is available 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.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 “Federal awarding agency review of risk posed by applicants.” This provision will apply to all NIH grants and cooperative agreements except fellowships.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/index.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-individuals/section-1557/index.htmlhttps://www.hhs.gov/civil-rights/for-providers/laws-regulations-guidance/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
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, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
NIH Working Group (NIH WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH as well as the Office of the Director. This group will be primarily responsible for the stewardship of the HuBMAP Program and will participate as non-voting members in the Consortium committees. The HuBMAP WG is led by the HuBMAP Program Manager and co-chaired by the Directors of NIBIB, NHLBI, and NIDDK. It reports to the Directors of the Office of Strategic Coordination/Common Fund and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.
HuBMAP Program Manager: The HuBMAP Program Manager is an NIH extramural scientist who is responsible for overall coordination of the Consortium and chairs the NIH WG. They will have substantial involvement in assessing progress and making recommendations about future funding. The HuBMAP Program Manager will have substantial scientific programmatic involvement in the direction of all the HuBMAP awards and may consult other NIH and non-NIH experts in making determinations. They will participate as a non-voting member of all Consortium committees and will review and approve Consortium policies. The HuBMAP Program Manager will not co-author publications with project investigators.
HuBMAP Program Coordinator - One or more NIH Program Staff will serve as Program Coordinators. The HuBMAP Coordinator will have substantial programmatic involvement that is above and beyond the normal stewardship role. The Coordinator will provide cooperation or coordination with, or assistance to, awardees in performing project activities. If feasible, the Coordinator will connect awardees with NIH-supported research resources and identify other researchers or resources that may accelerate the project. The Coordinator will also assist with connecting investigators to other federal agencies, similar consortia and related fields of research. The Coordinator will not co-author publications with project investigators.
Steering Committee (SC): The purpose of the SC is to recommend direction for the HuBMAP Consortium consistent with the program goals, develop Consortium policies and projects to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges and opportunities for the Consortium. The SC will include PDs/PIs of each of the awards and NIH WG members. The SC will be chaired by two PD/PIs that are approved by the NIH WG. An Executive Committee (EC) composed of the co-chairs and the NIH Program Team Leads will meet to set the agenda for SC meetings. The SC will establish subcommittees to oversee the development and implementation of Consortium policies including data release, publications and standards. It is expected that most of the decisions on the activities of the HUBMAP Steering Committee will be reached by consensus. If a vote is needed, each project PD/PI (or Contact PI in the case of multi-PI projects) will have one vote. NIH staff will be non-voting members of the SC but will review and approve policies developed by the Steering Committee. When a vote is required, at least 60% of the votes will be required for approval. Steering Committee recommendations will go to the HuBMAP Program Manager and the NIH Working Group for approval.
External Program Consultants (EPCs): As part of the HuBMAP program, NIH staff will engage 5-10 external program consultants (EPCs) not funded as part of the program but with relevant scientific and consortium experience to provide input and advice to the NIH WG. This could include reviewing and evaluating the progress of the entire HuBMAP Program or individual awardees as well as recommending changes in priorities for the HuBMAP Program based on scientific advances within and outside of the Consortium. The EPCs will be senior, scientific experts who are not directly involved in the activities of the HuBMAP Program and who agreement to a confidentiality policy, engaged on an as-needed basis to advise on specific issues. NIH is solely responsible for appointing EPCs for variable durations of service. EPCs are invited to participate in Consortium meetings and Steering Committees calls and the annual investigators’ meeting. A subset of EPCs may also meet by phone or web at other times of the year, as needed. Annually, the EPCs will provide individual assessments to the NIH of the progress of the Consortium and will present individual expert recommendations regarding any changes in the HuBMAP Program as necessary. The assessments and recommendations will be provided through the NIH WG to the Director of the Office of Strategic Coordination, NIH
HuBMAP Consortium: The HuBMAP Consortium is made up of HuBMAP awardees, the NIH WG and other scientists and groups the SC agrees to include within the Consortium. The Consortium structure is meant to efficiently and effectively guide all the funded projects to meet the overall goals of the HuBMAP Program.
For each individual award, NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NIH Program Officer - A NIH Program Officer (PO) is responsible for the normal scientific and programmatic stewardship, including monitoring progress and compliance with general statutory, regulatory, or policy requirements; discussing and approving milestones and significant changes to the project; and technical assistance to correct performance and facilitate interactions. The PO must approve in advance and in writing annual milestones and any significant changes to the award. The PO also has the option to recommend to the HuBMAP Program Manager, following consultation with the Project Scientist(s), ESCs or the NIH WG, restricting an award based on progress towards milestones, to incentivize rapid development and implementation of policies or collaboration between members of the consortium, or generation of data or resources for use by Consortium members or the wider community. NIH also reserves the right to modify the budget or duration of funding or to curtail an award in the event of: (a) substantive changes in the project not approved in advance, (b) use of funds for activities not within the scope of the specific aims, (c) failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved Consortium Policies, (d) failing to comply with the terms and conditions of the award or establish necessary statutory, regulatory, policy approval required for conducting the project, or (e) ethical or conflict of interest issues. The Program Officer will not co-author publications with project investigators.
NIH Project Scientist(s) - One or more NIH Program Staff will serve as Project Scientists (PSs), for each HuBMAP award and, as appropriate, to oversee collaborative projects amongst awardees and/or other Consortium members. The PSs will serve as the scientific representatives of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. If there is more than one PS, one of them will be designated as the Lead PS. The PSs will provide substantial NIH scientific programmatic involvement with the awardee that is anticipated during the performance of the activities supported by this Cooperative Agreement, including review of milestones. PSs will work closely with the PD/PI, the Steering Committee, and the PIs of all projects/cores to maximize progress towards the goals of the project and the program.
The PD(s)/PI(s) will have the primary responsibility for:
NIH Staff Involvement
The NIH will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award. NIH staff may have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility
Close interaction among the participating investigators will be required, as well as significant involvement from the NIH during each phase of the program. The awardees, the PSs, and other designated NIH Staff will participate in the annual in-person investigator meeting and scheduled conference calls and share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings. EPCs will attend the annual in person meetings. Other government staff may also attend the annual investigators meetings.
The SC will serve as the main scientific body of the Consortium, with the following roles:
It is anticipated that multiple subcommittees may need to be formed to address important topics. Current working groups 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 will be convened. The panel will have three members: a designee of the SC 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.
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.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 – Award Term and Conditions for Recipient Integrity and Performance Matters.
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
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Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Pothur Srinivas, Ph.D., MPH
National Heart, Lung, and Blood Institute (NHLBI)
David Balasundaram, Ph.D.
Center for Scientific Review
National Heart, Lung, and Blood Institute (NHLBI)
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