Part 1. Overview Information

Key Dates

All applications are due by 5:00 PM local time of applicant organization. 

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.

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide, except where instructed to do otherwise (in this NOFO or in a Notice from NIH Guide for Grants and Contracts).

Conformance to all requirements (both in the How to Apply - Application Guide and the NOFO) is required and strictly enforced. Applicants must read and follow all application instructions in the How to Apply - Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the How to Apply - Application Guide, follow the program-specific instructions.

Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 2. Full Text of Announcement

Section I. Notice of Funding Opportunity Description

Purpose

This Notice of Funding Opportunity (NOFO) invites applications for the NIH/Center for the Advancement of Science in Space (CASIS) Coordinated Microphysiological Systems Program for Translational Research in Space (Tissue Chips in Space 2.0), for projects designed to develop automated, complex organ Microphysiological Systems (MPS) representing the broad spectrum of population diversity to assess the effects of microgravity on the human body. The overall objective of the program is to better understand the effects of microgravity on human physiology as models of disease, to gain insight into the hallmarks of human age-related tissue and organ functional decline, to uncover the mechanisms underlying age-related disorders, and to provide opportunities for the development of new therapies for age-related dysfunction and associate diseases leveraging MPS operating in microgravity. This NOFO focuses on further development of tissue-on-chip technology applied to research conducted on the International Space Station National Laboratory (ISS-NL) in low Earth orbit to advance the discovery of diagnostic biomarkers and therapeutic interventions for diseases of aging, including MPS platforms that leverage recent advances in the longevity extensions of MPS. An essential feature of this NOFO is an expectation for a multidisciplinary approach that brings together experts in bioengineering, computational biology, aging biology, diseases of aging and pathology, pharmacology, drug development and clinical science. This NOFO will ultimately advance biomedical research and clinical technologies for terrestrial and space use that could improve human health on Earth and in space.

Funds from the NIH will be made available through the cooperative agreement award mechanism using the UG3/UH3 activity code. The initial UG3 phase will support studies to develop multi-organ automated MPS and test them on the ground and onboard the ISS-NL. Funds will be utilized to conduct preflight ground development and validation of multi-organ MPS, National Aeronautics and Space Administration (NASA) flight certification to support in-orbit experiment operations, and post flight data processing. The UH3 phase will support studies that build upon findings from the UG3 phase. Funds will be utilized to conduct preflight ground optimization and validation, NASA flight certification to support in-orbit experiment operations, and post-flight data processing to facilitate the assessment of biomarkers, bioavailability, efficacy, and toxicity of therapeutic agents. CASIS, Inc., a nonprofit organization that manages the ISS National Laboratory on the International Space Station, will facilitate access to the services of commercial implementation partners with expertise in the execution of microgravity research in space, provide access to NASACargo Resupply Services vehicles for the transportation of experiments to the ISS-NL, support for the execution of experiments on the ISS-NL by crew, and return of the experiments from the ISS-NL to the ground for both the UG3 and UH3 phases.

Background

The International Space Station National Laboratory (ISS-NL) provides an extraordinary research platform for experiments in the biological and medical sciences. Microgravity induces a vast array of changes in organisms ranging from bacteria to humans, including global alterations in gene expression and 3-dimensional aggregation of cells into tissue-like structures. Moreover, studies of astronauts reveal a variety of space flight-induced health conditions, many of which may serve as models of ground-based ailments such as aging, age-related diseases and trauma. Many of these alterations in human physiology resemble those observed during the process of aging, but at accelerated pace in microgravity conditions. Microphysiological Systems (MPS) are bioengineered microfluidic devices seeded with human cells and tissues that recapitulate organ systems and function. MPS have emerged as powerful tools for biomedical research and are gaining essential roles in drug discovery, regulatory approval, safety and efficacy assessment and precision medicine studies. NCATS has consistently shown leadership in the development of tissue chip technology, in the demonstration of its utility in drug development for safety, efficacy and precision medicine, and in the dissemination of the technology (https://ncats.nih.gov/tissuechip/about).  NCATS previously funded a Chips-in-Space consortium which further developed MPS systems to be used in low Earth orbit (LEO) biomedical research under microgravity conditions (https://ncats.nih.gov/research/research-activities/tissue-chip/projects/space). Through partnerships between NCATS, NASA and CASIS, the Tissue-Chips-in-Space program has enabled advances in the study of microgravity-associated human physiology. The Tissue-Chips-in-Space program has also promoted key technological improvements in the tissue chips instrumentation systems towards automation and miniaturization required for space flight.

Research into the effects of the space environment on human tissues and organs promises to advance pharmaceutical development and augment Earth-based studies in human biology. The NIH and CASIS have partnered and executed a memorandum of understanding (MOU) to collaborate and coordinate efforts that will help refine tissue chip technology for biomedical research use at the ISS-NL. The ability to conduct research in space using tissue chip technology provides unprecedented opportunities to study the effects of microgravity, reduced-gravity environments at the ISS-NL, and radiation exposure and its effects on many of the human body's systems. Several human body systems weaken or deteriorate when subjected to a microgravity environment during spaceflight mimicking earth-bound functional changes – cardiac dysfunction, sarcopenia, bone density loss, decreased visual acuity, fibrosis, wound healing and immuosenescence. These physiological changes closely mirror some age-related disease states, except that microgravity-induced changes often manifest clinically-relevant markers more rapidly in space, resulting in detectable changes that occur over weeks or months compared to years and decades on Earth. In addition, host-microbial interactions can be affected due to the impact of microgravity on the immune system and provide an opportunity to understand shifts of microbial communities (e.g. pathobionts) that promote a dysbiotic state, and the systemic effects of microbially-derived metabolites on host physiology. This accelerated onset and progression provides an opportunity to model diseases in space and to gain insights into the mechanisms controlling age-related dysfunction at a faster pace. Similarly, the identification and testing of therapeutic targets could be accelerated. The development of potential therapeutics targeting aging-related dysfunctions is notoriously difficult. In clinical trials, progression is slow with a typical clinical trial length and optimal timing of intervention not aligning with symptoms, progression is not formally captured in routine care and is difficult to ascertain. Therefore, microgravity conditions could potentially provide unique opportunities for conducting clinical trials for therapeutics targeting aging dysfunction and age-associated diseases. This Tissue-Chips-in-Space 2.0 program will support development of multi-organ integrated tissue chip and organ-on-a-chip platforms to more closely approximate human body-on-chip systems and better model physiological changes associated with aging and related diseases. Multi-organ platform integration will enable the study of multiple organ (patho)physiology including organ-to-organ communication and host-microbiome interactions in diseased and healthy models. The use of induced pluripotent stem cell (iPSC)-derived organ-specific cell types from diverse groups of donors, which may, in the future, include those from NASA and commercial astronauts who will serve as their own avatars, will enable advances in the study of microgravity-associated age-related conditions mimicking accelerated aging pathophysiology that take into account disease heterogeneity and/or population diversity.

To improve MPS platform technology for utilization as model systems to better understand the effects of space on humans during long-duration spaceflights, NASA partnered with the NIH, Biomedical Advanced Research and Development Authority (BARDA) and the Food and Drug Administration (FDA) to develop extended longevity tissue chips for development and testing on Earth with a focus on the development of systems requiring minimal human intervention. The funded projects seek to adapt existing 3D tissues and MPS to expand tissue viability and robust function for a minimum of 6 months and fully test and validate these models in response to acute and chronic stressors (https://science.nasa.gov/mission/3d-tissue-chips). This program will incorporate automated engineering capabilities for real-time online readouts for longitudinal data capturing. The Tissue Chips in Space 2.0 program may incorporate these and other advancements in tissue chips technology, such as extending MPS culture viability beyond a month in order to extend experimental time to advance our understanding of age-related conditions. The Tissue-Chips-in-Space 2.0. program is intended to benefit from lessons learned during the development of improved automation and miniaturization of these MPS platforms and contribute to the development of integrated automated and miniaturized MPS systems supported by the MATChS program.  These technologies, further developed in the Tissue-Chips-in-Space 2.0 program, will provide opportunities to study the effects of long duration space flight on the human body that not only inform us about the effects of space on human health, but also advance our understanding of human (patho)physiology on Earth.  It is anticipated that this NIH/CASIS NOFO will delve into the molecular basis of physiological events in a microgravity environment which recapitulate human aging processes at an accelerated rate. This program will provide information on human age-related dysfunction and age-associated diseases and will accelerate the discovery of molecular mechanisms providing information for novel targets for drug development and innovative treatment modalities. Thus, the program will contribute to the development of drugs that can slow the process of aging and will lead to new interventions that can target a range of common human age-related disorders. 

Partner Organizations

The highly collaborative nature of these projects will require close interactions with the following Partner Organizations. A collaborative partnership with both CASIS and an Implementation Partner is required. In addition, award recipients will be required to participate in the Tissue Chip Consortium, as described below.

CASIS:

CASIS manages the International Space Station ("ISS") National Laboratory ("NL") in accordance with NASA Cooperative Agreement No. 80JSC018M0005, CFDA 0043-007. In partnership with NASA, CASIS works to enable access to the ISS National Lab for research, technology development, STEM education, and workforce development by U.S. commercial companies, U.S. government agencies, and U.S. educational and nonprofit organizations that require the unique environment of space for projects seeking to improve lives and the health of patients on Earth.  As with the prior Tissue-Chips-in-Space program and at no cost to the recipients, CASIS will again allocate in-kind resources that will be utilized to enable the NIH-awarded spaceflight investigations. These in-kind resources will include, but are not limited to, a portion of the total scope spaceflight mission management, the required services for the transportation of flight hardware, experiments, and samples to and from the International Space Station, the in-orbit astronaut crew time required for experiment execution, as well as other resources and coordination activities as are necessary to conduct the awarded microgravity investigations. CASIS will also provide the following to NCATS recipients:

• Coordinate with recipients to obtain final approval and manifest for flight by NASA.
• Coordinate with NASA and the recipient's selected Implementation Partner for in-orbit access to appropriate testing facilities. It is anticipated that ISS-NL and its Implementation Partner will support recipients in arranging for the required flight to the ISS-NL. Assist recipients by coordinating with third parties, including NASA and the Implementation Partner, in order that recipients may obtain appropriate resources to allow them to effectively conduct research and development on the ISS-NL.
• Assist recipients to identify and coordinate ground-based pre-flight and post-flight resources at launch and primary landing or alternate landing sites.
• CASIS and NIH will prioritize the recipient's research prior to sending to NASA for its integrated prioritization and approval. If approved, CASIS will coordinate in-orbit space flight on the ISS-NL.

Recipients of an NIH award will be required to enter into a User Agreement with CASIS for the support of the ISS National Lab to sponsor the research investigation on the International Space Station. The ISS-NL User Agreement template is available here ( https://www.issnationallab.org/user-agreements/ ) and includes additional requirements from NASA as well as the terms and conditions that will govern the partnership between NIH grant recipients and CASIS for payload development and the execution of the research investigation on the International Space Station.

Implementation Partners:

Each recipient will be required to select and work with an Implementation Partner. Implementation Partners are experienced commercial companies who design and build spaceflight hardware and provide services to the research community as science payload developers. In partnership with CASIS, their expertise in hardware design and the payload integration process coupled with demonstrated experience in space is intended to ensure scientific success even for recipients who may have no or limited prior spaceflight research. Implementation Partners provide unique suites of flight certified hardware and services including:

• Technical guidance to translate ground-based science goals to the space environment
• Engineering integration
• Hardware/software development and testing
• Flight qualification services
• Mission management
• Launch
• Landing site support
• Operations planning and real-time crew operations support

Contact information for ISS-NL Implementation Partners and introductory information on their capabilities can be found at https://www.issnationallab.org/implementation-partners/. It is anticipated that the applicants determine the detailed plan for integration of the developed multi-organ MPS system with hardware for space experiments in collaboration with the selected Implementation partner. Such plans should be included in the Research Strategy section of the application and appropriately budgeted in the Budget section of the application. 

The Tissue Chip Consortium (The TC Consortium)

The NIH Tissue Chip Programs are led and managed by NCATS and utilize expertise (organ physiology, regulatory science, stem cells, bioengineering, etc.) from NIH experts, as well as experts from the FDA and industry. The TC Consortium, which comprises all these partnerships, holds an in-person meeting every 6 months and plays a pivotal role in advancing MPS technology.  Recipients from this NOFO will become members of the TC Consortium and will be expected to attend these semi-annual meetings.

Research Objectives and Scope

This initiative supports translational research using tissue chips to investigate the effects of microgravity and the spaceflight environment on the human body. The findings will provide mechanistic insights into how the microgravity environment models aging and diseases associated with aging, particularly, but not exclusively, in integumentary, skeletal, muscular, nervous, endocrine, cardiovascular, immune, respiratory, digestive, urinary, and reproductive systems. Research designed to improve the translation of existing knowledge into strategies for the prevention and treatment of such diseases or conditions in humans will be responsive to this NOFO. Development of integrated complex organ system by using iPSC-derived organ-specific cell types from diverse groups of people is expected in this NOFO. A complex organ system may be a multi-organ or single organ MPS well mimicking organismal function, for example by introducing hormones or lymphokines/chemokines. Multi-organ Integrated MPS system may be a system comprised of more than one tissue/organ affected in healthy aging and age-related diseases. Multi-organ system can be comprised of individual organ/tissue integrated in one MPS, or co-culture of different organ/tissues including vascularization, innervation, incorporation of immune cells. This complex organ system should allow for modeling of aging and age-related conditions with higher precision.  Multi-organ signals are regulated during aging and aging-related changes in interorgan communication may play a significant role in aging pathology. In this multi-organ system, it is also of interest to assess any changes in the physical and functional characteristic of exosomes or extracellular vesicles as important mediators of intercellular signaling and communication under microgravity. Understanding the mechanisms that coordinate organ interactions may lead to new insights into multi-morbidities. Incorporation of population diversity in the MPS will allow for better understanding of the complexity and heterogeneity of aging and associated pathologies and will lead to better characterization of the hallmarks of aging, such as epigenetic alterations, changes in telomere length, shift in multi-omic (transcriptomic, proteomic, and metabolomic) profiles, post-translational modifications and dysbiosis. Cellular senescence may be triggering aging and could be considered as a therapeutic target for treating aging-related pathologies and chronic diseases, e.g., cancer, neurodegeneration, heart disease and osteoarthritis. The outcomes of this program will contribute to the development of senescence biomarkers and identification of therapeutic targets. 

The identification of targetable molecular pathways will contribute to facilitating translation into strategies for the prevention and treatment of aging-related conditions and diseases. It is anticipated that the funded projects will develop integrated automated and miniaturized MPS capable of functioning autonomously for extensive periods of time. These systems should be equipped with capabilities to maintain culture without external intervention and to be monitored remotely through real-time biosensing and readout capabilities, including telemetry operations. MPS will be subject to post flight recovery for tissue (e.g., histological) and multiomic (e.g., genomic, proteomic, metabolomic, epigenomic) analyses to elucidate the pathways affected by microgravity, to identify hallmarks of aging accelerated by the permanence in space, and to assess biomarkers of aging-related conditions. The newly acquired knowledge will enable novel pharmaceutical design/targets based on a better mechanistic insight of the biology.

Each UG3/UH3 application should be structured to meet the NIH/CASIS program goals. It is anticipated that the UG3 phase will involve on-ground development of multi-organ automated tissue chip technology to be used in microgravity environments. That includes, but it is not limited to, working with the ISS-NL and ISS-NL Implementation Partners to design, develop, and execute ground testing of flight hardware in pilot experiments to validate that all of the science objectives defined for the proposed experiment can be completed prior to flight integration for launch to the International Space Station and execution on orbit. Successful UG3 projects may transition into the UH3 phase for re-flight and more extensive experiments and analyses, with no more than 5 years of support for UG3/UH3 phases. The models are expected to recapitulate critical aspects of human physiology and to provide a measurable output for the representative systems. It is expected that iPSC from diverse groups of donors will be used in developing multi-organ tissue chips that will allow more accurately represent human physiology and pathology. Factors contributing to diversity that can influence the risk and likelihood of developing a disease, experiencing a long-term health outcome, and responding to treatment include (but are not limited to):

• Age
• Biological sex
• Pregnancy status
• Life experiences (negatives, such as psychosocial stress and lack of basic resources, or positives, such as educational and employment opportunities)
• Unhealthy behaviors (e.g., substance use, sedentary lifestyle, overeating, risky sexual activity)
• Health-promoting behaviors (e.g., adequate sleep, obtaining recommended preventive services, physical activity, healthy eating)
• Environmental conditions (e.g., pollution, access to health care or healthy foods, neighborhood segregation)
• Genetic variation and geographic ancestry
• Underlying medical problems or presence of comorbidities (i.e., additional diseases or conditions)

Essential characteristics of the models should include all or some of the following features: 1) multi-cellular architecture that represents characteristics of the healthy tissues or organs and their pathology; 2) functional representation of normal and diseased human biology; 3) reproducible and viable operation under physiological conditions maintained for extended periods of time; and 4) representation of diversity and heterogeneity of human population.  The platform used should be compatible for operation at the ISS-NL using ground-based controls, transmit to ground control assay outputs that include telemetry operation for different types of read-outs depending on particular multi-organ system architecture. The platform should also provide spatial and temporal control of the cellular microenvironment, while enabling continuous monitoring (sensing), probing (direct in-cell measurements), and sampling (testing and continuous data collection and analysis) of the system. Particularly, the monitoring of fluidic control, oxygen and pH in-line sensors is expected.

At least one flight opportunity is expected for each of the UG3 and UH3 phases, and therefore a flight experiment should be proposed for each of the UG3 and UH3 phases. Selected projects should be flight ready within 18 months of the specific award period, but it will not be possible to secure flight allocation resources on the International Space Station for all flight-ready projects in this time interval if multiple investigations mature at the same time.  If flight schedules change, investigators may modify proposed timelines, subject to review and approval by the NIH Program Officer in coordination with ISS-NL.

This application will be administered as a bi-phasic award.  The entire project period (combined UG3 and UH3) should not exceed five years. Applicants may propose a project period of up to two to three years for each phase depending on project needs. Please note below the major goals that are anticipated to be accomplished under each phase of award.   

Major Goals of the UG3 phase:

(1) develop complex-organ MPS system using iPSC-derived or primary patient cell sources on tissues/organ-on-chips platforms with platform integration to study organ pathology and organ-to-organ communication. Strong justification and rational for cell source used should be provided.  Models should demonstrate a functional representation of normal and diseased human states representing population diversity. These MPS systems should be developed to be functional in automatic regime for prolonged periods of time and be capable of telemetry for continuous monitoring of the system. These miniaturized systems should be capable of integrating with the flight-certified hardware for payload and functioning in an automatic regime. (2) determine the relevance of models via preliminary testing of key experimental features and outcomes on the ground and during the initial flight to the ISS-NL. The successful outcome will determine which UG3 projects will proceed to the UH3 phase of the study. This would include, for example, inclusion of non-invasive endpoints that generate reproducible data under physiological conditions over a prolonged culture conditions at the ISS-NL. The functional validation of the tissue chips may be model-specific.

Major Goals of the UH3 phase:

(1) to demonstrate the functional utility of the models for understanding the effects of microgravity on human physiology, (2) to correlate these effects with hallmarks of aging and markers of age-associated conditions, (3) to identify novel targets for drug screening, (4) to assess candidate therapies for efficacy and safety. These goals will lead to the establishment of pre-clinical foundations that will inform clinical trial design. To achieve this, the applications should focus on outcomes that may include:

• Cross-validation of model end-points with clinical measures in humans
• Characterization of the parameters of response to exposure to the space environment on the ISS-NL
• Developing translatable pharmacodynamics (i.e., target engagement) biomarkers for well-validated therapeutic targets
• Conducting preclinical efficacy testing of candidate therapeutics using innovative approaches, data acquisition and analyses
• Extensive characterization and clinico-pathological staging in the models with the corresponding stages of clinical disease using translatable biomarkers
• Developing strategies for rapid, open-access dissemination of data, and methodology, for rapid distribution of models for their use in a therapy development

Transition from the UG3 to the UH3 Award

Transition to the UH3 award will depend on the successful achievement of general and model-specific benchmarks, the feasibility of study continuation, a proven ability to work within a consortium arrangement with other recipients and ISS-NL Implementation Partners, and the availability of funds. Not all award recipients may transition from the UG3 to the UH3 phase of award. The UH3 award consideration will be determined through an administrative review of progress in the UG3 phase focused on UG3 recipients who successfully met their milestones, demonstrated functionality and validity of their model systems, and have well-conceived plans to fully utilize the models for more extensive testing on the ISS-NL during the UH3 phase. The Administrative review determining conversion to the UH3 phase will be conducted by a panel derived from the Tissue Chip Project team, composed of NIH extramural program staff from the participating NIH Institutes. Successful completion of the UG3 milestones will be the basis for determination on whether the application should progress to the UH3 phase. ISS-NL will provide input to NIH extramural program staff on the feasibility of the projects for the next phase.

Recipients will submit a progress report to both the Grants Management Specialist and the NIH Program Official upon completion of the UG3 milestones. The progress report may also include updates and revisions to the originally proposed UH3 aims based on the results of the UG3 phase.  Prior to initiation of the UH3 stage, an updated human subjects protection plan (e.g., protocol amendment, IRB approval of amendments to the protocol or consent form, etc.) and a detailed data and safety monitoring plan (DSMP), if appropriate, must be approved by NIH.

Milestones and Timeline: 

A timeline (Gantt chart) to include milestones is required for all studies. Milestones are benchmarks that create go/no-go decision points in the project and must include clear and quantitative criteria for success. Yearly quantitative milestones are required to provide clear indicators of a project's continued success or emergent difficulties. Milestones 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. This NOFO is designed as a two-stage cooperative agreement. Applications must include the anticipated milestones for both the UG3 and the UH3 phase. The UG3 must include milestones to determine the success of the project at the end of the UG3 phase. Support for the UH3 is contingent upon progress made during the UG3 phase, meeting the milestones, programmatic priorities, the original UG3/UH3 peer review recommendations, and the availability of funds. Some projects may not transition from the UG3 to the UH3 phase.

Prior to funding an application, the Program Official will contact the applicant to discuss the proposed UG3 and UH3 milestones and any changes suggested by NIH staff or the NIH review panel. The Program Official and applicant will negotiate and agree upon a final set of approved milestones which will be specified in the Notice of Award. Selected projects must be flight-ready within 18 months of the UG3 award start date.

Technical Feasibility

In order to utilize the ISS National Lab, NASA has specified details regarding payload integration requirements available at https://www.nasa.gov/missions/station/quick-start-guide-to-payload-design/. The ISS-NL requires that recipients identify an Implementation Partner that has experience developing NASA flight certified payloads and to develop with the Implementation Partner an experimental concept with defined science requirements in the flight hardware and/or facility supported by the Implementation Partner. A list of Implementation Partners is available at https://www.issnationallab.org/implementation-partners/ and general questions regarding the capabilities of flight hardware and facilities on the International Space Station may be sent to a CASIS representative at [email protected].  Please contact CASIS and NIH program staff with any questions or concerns.

Investigators must contact a CASIS representative, at [email protected], as early as possible to receive guidance on the technical feasibility component of their applications prior to submission to the NIH.  This interaction with CASIS is crucial for providing guidance on which ISS-NL Implementation Partner would be most appropriate for partnering with the applicant. Implementation Partners are experienced payload developers and subject matter experts who can provide a wide range of products and services to aid in the payload integration process and have demonstrated experience to ensure scientific success. It is expected that the effort of the Implementation Partner will be budgeted as a subcontract.

Recipients may be required to travel to support critical project activities related to experiment design/development, payload development, experiment and payload verification testing, design reviews, ISS crew training, and/or other required ISS payload integration process requirements.

National Institute on Aging ( NIA )

The National Institute on Aging (NIA) is interested in using the unique ISS-NL environment to study aging and age-related processes in humans with a focus on understanding molecular, cellular, and physiological mechanisms.

While applications are primarily centered around MPS technology development for experimentation in space to improve human health, one or more of the aims should address specific questions about the biology of aging in low gravity and on earth. NIA is interested in approaches that promote understanding of aging cells and tissues. 

Examples of meritorious projects that NIA may consider include but are not limited to: 1) comparisons between the mechanisms of aging-like phenotypes in space to aging phenotypes observed on the ground and 2) investigations of the influence of space flight on the hallmarks of aging.  

Applications that do not contain all of the required elements of the Research Strategy and attachments in the R&R Other Project Information Form, Other Attachments section will be deemed incomplete and will not be reviewed.

See Section VIII. Other Information for award authorities and regulations.

Section II. Award Information

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this NOFO.

Section III. Eligibility Information

1. Eligible Applicants

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Local Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)

Federal Governments

• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Organizations) 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 not allowed. 

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the How to Apply - 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. Failure to complete registrations in advance of a due date is not a valid reason for a late submission, please reference NIH Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications for additional information

• System for Award Management (SAM) – Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code – Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
  • Unique Entity Identifier (UEI) - A UEI is issued as part of the SAM.gov registration process. The same UEI must be used for all registrations, as well as on the grant application.
• eRA Commons - Once the unique organization identifier is established, organizations can register with eRA Commons in tandem with completing their Grants.gov registrations; all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov – Applicants must have an active SAM registration in order to complete the Grants.gov registration.

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 their organization to develop an application for support. Individuals from diverse backgrounds, including underrepresented racial and ethnic groups, individuals with disabilities, and women are always encouraged to apply for NIH support. See, Reminder: Notice of NIH's Encouragement of Applications Supporting Individuals from Underrepresented Ethnic and Racial Groups as well as Individuals with Disabilities, NOT-OD-22-019.

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 How to Apply - Application Guide.

2. Cost Sharing

This NOFO does not require cost sharing as defined in the NIH Grants Policy Statement NIH Grants Policy Statement Section 1.2 Definition of Terms.

3. Additional Information on Eligibility

Number of Applications

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, per NIH Grants Policy Statement Section 2.3.7.4 Submission of Resubmission Application. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NIH Grants Policy Statement 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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 NOFO. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the Research (R) Instructions in the How to Apply - Application Guide except where instructed in this notice of funding opportunity to do otherwise. Conformance to the requirements in the How to Apply - Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Letter of Intent

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:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

NCATS Letters of Intent
Telephone: 301-827-9549
Email: [email protected] 

Page Limitations

All page limitations described in the How to Apply – Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the How to Apply – Application Guide and should be used for preparing an application to this NOFO.

SF424(R&R) Cover

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the How to Apply - Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Other Attachments:

Milestone Plan (required): The filename "Milestone Plan.pdf" should be used.

The Milestone Plan attachment is limited to 2-page maximum. Applications lacking a Milestone Plan attachment will be considered incomplete and will not be reviewed.

The applicant is required to provide detailed information and timelines for completing all proposed activities according to the Specific Aims. A separate timeline and milestones must be included for each phase (UG3 and UH3), and Milestones should refer to Specific Aims and include the following:

• detailed quantitative criteria by which milestone achievement will be assessed
• detailed timeline for the anticipated attainment of each milestone and the overall goal and
• any impediments that could require an addendum to the research plan, milestones, or timeline with a discussion of alternative approaches.

Milestones that reflect progress in each specific aim should be easily measurable and realistic. Include specific criteria against which project progress will be assessed.

Go/No-Go Transition Milestone for transition from the UG3 Phase to the UH3 Phase

• The UG3 must include clearly identified go/no-go transition milestones to determine the success of the project at the end of this phase for transition to the UH3 and for continued funding.

Provide a graphical display summarizing the timeline of the milestones plan in the form of a Gantt Chart.

SF424(R&R) Senior/Key Person Profile

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Within the biosketches, examples must be included of the PD(s)'/PI(s)’ experience in directing research activities related to Microphysiological systems.

Within the biosketches, include information about the personnel's expertise of the scientific fields relevant to this NOFO, i.e., expertise in bioengineering, computational biology, aging biology, diseases of aging and pathology, pharmacology, drug development and clinical science.

R&R Budget

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

A Senior/Key personnel representative from a team is required to attend a semi-annual NIH TC Consortium Meetings in the Washington, D.C. area. Funds to support travel of this representative to attend the Consortium Meetings should be included in the budget.

Applicants should also request funds for travel expenses related to critical project activities related to experiment design/development, payload development, experiment and payload verification testing, design reviews, ISS crew training, and/or other required ISS payload integration process requirements after interaction with Implementation Partner to define the anticipated frequency, location, and approximate budget of travel.

Applicants must include the proposed budget for both the UG3 and UH3 phases of the award. 

R&R Subaward Budget

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Funds required for ISS payload optimization by Implementation Partner and MPS ISS payload integration should be included in the budget as a subcontract to Implementation Partner.

PHS 398 Cover Page Supplement

All instructions in the How to Apply - Application Guide must be followed.

PHS 398 Research Plan

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

Specific Aims: Provide the overall goals or hypotheses for the entire project period and indicate separate Specific Aims to be accomplished in the UG3 phase and in the UH3 phase.

Research Strategy: Applicants should provide a rationale for the choice organs and human body systems modeled in multi-organ MPS system and the rationale for how experiments in space will advance the study of human (patho)physiology, in particular the process of aging and associated diseases. A detailed description of plans to develop a bioengineered platform using advances in Microphysiological systems engineering, biosensing and other cutting-edge technologies is expected. These plans should include characterization of these systems duration or length of culture, discussion of candidate therapies including timing of administration, appropriate assays, biomarkers and physiological readouts, and statistical analyses, including experimental replicates and ground controls. It is required that the plans will include the use of iPSC-derived organ-specific cell types from diverse groups of people, to enable advances in the study of microgravity-associated age-related conditions mimicking accelerated aging pathophysiology considering disease heterogeneity and/or population diversity. Applicants are required to include an identified implementation partner from the list of CASIS Implementation Partners, which can be found at https://www.issnationallab.org/implementation-partners/, and should include a description of the proposed interactions with CASIS Implementation Partners to satisfy NASA payload integration requirements, as well as the approaches to characterize the models and identify novel biology/mechanisms that could aid in novel targets for treatment.

• Provide separate sections that describe both the UG3 and UH3 phases
• Provide a separate section addressing how NASA payload integration requirements will be met
• Provide a description of the hypothesis to be tested in the UG3 phase of the study
• Include a discussion of past collective experience and successes with the preclinical studies proposed and experience developing required documentation for the conduct of related clinical studies
• A description of the consortium arrangement with CASIS Implementation partners to meet the program goals

Technical Feasibility (required)

Applications must clearly describe how the NASA payload integration requirements will be met. Specifically, the technical feasibility details should include logistics, hardware, projected time frame, hazards, and research questions. Applications may be considered technically incomplete for flight research if a detailed description of proposed flight hardware with spatial and temporal control of the cellular microenvironment is not included, and the NASA payload integration requirements are not addressed. Such applications deemed incomplete will not be reviewed.

Specifically, the technical feasibility details should include the following elements:

• Logistics: Proposed resources including Implementation Partner support, facility needs for ground testing and flight operations support, use of ISS crew for research support, power and data requirements, weight, and any known hazards
• Hardware: Availability, limitations, appropriate planned use and (alternatively) the costs and feasibility of proposed new hardware development
• Projected Time Frame: Preflight development and testing considerations, time to flight and time to completion
• Hazards: Procedures, situations and materials that could potentially be hazardous and a plan to mitigate any identified issues

Applications must contain the following elements/items to be considered complete. All applications that do not contain these elements will be considered incomplete and will not be reviewed:

• Applications must contain an identified Implementation Partner from list of CASIS Implementation Partners.
• A Technical Feasibility section within the Research Strategy. 
• Detailed plans on how the proposed MPS representing diverse population will be developed and integrated with flight-certified hardware in the payload.
• Address the NASA payload integration requirements.
• Proposed use of the ISS-NL for experiments in both the UG3 and UH3 phases of the project.
• Proposed budget and milestones for both the UG3 and UH3 phases of the project.

Letters of Support: A Letter of Support from the Implementation Partner is required.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the How to Apply - Application Guide.

Other Plan(s): 

All instructions in the How to Apply - Application Guide must be followed, with the following additional instructions:

• All applicants planning research (funded or conducted in whole or in part by NIH) that results in the generation of scientific data are required to comply with the instructions for the Data Management and Sharing Plan. All applications, regardless of the amount of direct costs requested for any one year, must address a Data Management and Sharing Plan.
• The Data Management and Sharing Plan should include a plan to ensure all study materials, tools, databases and procedures developed from the project are broadly available to the scientific community and the NIH within 90 days of the end of the study.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the How to Apply - Application Guide.

• No publications or other material, with the exception of blank questionnaires or blank surveys, may be included in the Appendix.

PHS Human Subjects and Clinical Trials Information

When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the How to Apply - Application Guide, with the following additional instructions:

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 How to Apply - 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 How to Apply - Application Guide must be followed.

PHS Assignment Request Form

All instructions in the How to Apply - Application Guide must be followed.

3. Unique Entity Identifier and System for Award Management (SAM)

See Part 2. 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

4. Submission Dates and Times

Part I. 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 Grants Policy Statement Section 2.3.9.2 Electronically Submitted Applications.

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 How to Apply – Application Guide.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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 Section 7.9.1 Selected Items of Cost.

7. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the How to Apply - 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.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile form. 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 NOFO for information on registration requirements.

The applicant organization must ensure that the unique entity identifier provided on the application is the same identifier used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the How to Apply - 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 NCATS, 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 NCATS Referral Office by email at [email protected] when the application has been submitted. Please include the FON number and title, PD/PI name, and title of the application.

Recipients or subrecipients must submit any information related to violations of federal criminal law involving fraud, bribery, or gratuity violations potentially affecting the federal award. See Mandatory Disclosures, 2 CFR 200.113 and NIH Grants Policy Statement Section 4.1.35.

Send written disclosures to the NIH Chief Grants Management Officer listed on the Notice of Award for the IC that funded the award and to the HHS Office of Inspector Grant Self Disclosure Program at [email protected]. 

Post Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in the policy

Any instructions provided here are in addition to the instructions in the policy.

Section V. Application Review Information

1. Criteria

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.

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.

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.

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.

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Center for Advancing Translational Sciences, in accordance with NIH peer review policies and practices, 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 will receive a written critique.

Applications may undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.

Appeals of initial peer review will not be accepted for applications submitted in response to this NOFO.

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 NOFO. Following initial peer review, recommended applications will receive a second level of review by the National Center for Advancing Translational Sciences Advisory Council. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

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 Section 2.5.1. Just-in-Time Procedures. This request is not a Notice of Award nor should it be construed to be an indicator of possible funding.

Prior to making an award, NIH reviews an applicant’s federal award history in SAM.gov to ensure sound business practices. An applicant can review and comment on any information in the Responsibility/Qualification records available in SAM.gov.  NIH will consider any comments by the applicant in the Responsibility/Qualification records in SAM.gov to ascertain the applicant’s integrity, business ethics, and performance record of managing Federal awards per 2 CFR Part 200.206 “Federal awarding agency review of risk posed by applicants.”  This provision will apply to all NIH grants and cooperative agreements except fellowships.

3. Anticipated Announcement and Award Dates

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement Section 2.4.4 Disposition of Applications.

Section VI. Award Administration Information

1. Award Notices

A Notice of Award (NoA) is the official authorizing document notifying the applicant that an award has been made and that funds may be requested from the designated HHS payment system or office. The NoA is signed by the Grants Management Officer and emailed to the recipient’s business official.

In accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

Recipients must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Any pre-award costs incurred before receipt of the NoA are at the applicant's own risk.  For more information on the Notice of Award, please refer to the NIH Grants Policy Statement Section 5. The Notice of Award and NIH Grants & Funding website, see Award Process.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the recipient must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

2. Administrative and National Policy Requirements

The following Federal wide and HHS-specific policy requirements apply to awards funded through NIH:

• The rules listed at 2 CFR Part 200, Uniform Administrative Requirements, Cost Principles, and Audit Requirements for Federal Awards.
• All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the terms and conditions in the Notice of Award (NoA). The NoA includes the requirements of this NOFO. 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, Recipients, and Activities.
• If a recipient receives an award, the recipient must follow all applicable nondiscrimination laws. The recipient agrees to this when registering in SAM.gov. The recipient must also submit an Assurance of Compliance (HHS-690). To learn more, see the Laws and Regulations Enforced by the HHS Office for Civil Rights website. 
  • HHS recognizes that NIH 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. 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 NOFO.

All federal statutes and regulations relevant to federal financial assistance, including those highlighted in NIH Grants Policy Statement Section 4 Public Policy Requirements, Objectives and Other Appropriation Mandates.

Recipients are responsible for ensuring that their activities comply with all applicable federal regulations.  NIH may terminate awards under certain circumstances.  See 2 CFR Part 200.340 Termination and NIH Grants Policy Statement Section 8.5.2 Remedies for Noncompliance or Enforcement Actions: Suspension, Termination, and Withholding of Support. 

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 (HHS) grant administration regulations at 2 CFR Part 200, 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 recipients 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 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining the details and goals of the project as a whole within the guidelines of this NOFO.
• Determining experimental approaches, designing protocols, setting project milestones, and conducting experiments.
• Performing established standardization and benchmarking milestones.
• Adhering to the NIH policies regarding intellectual property, data release and other policies that might be established during the course of this activity.
• Coordinating, cooperating, and participating with NIH staff in the scientific, technical, and administrative management.
• Providing progress updates to the NCATS Program Officer and Project Scientist(s) and CASIS TC Project Team members on a regular schedule to be negotiated prior to award.
• Fully participating in the highly collaborative nature of the NIH Tissue Chips (TC) program led by NCATS.
• Participating in a cooperative and interactive manner with NIH staff, TC investigators and one another.
• Ensuring that the research is conducted in accordance with processes and goals as delineated in this NOFO.
• Ensuring that all affiliated staff will maintain the confidentiality of the information developed by the investigations, including, without limitation, informatics tools, protocols, data analysis, conclusions, etc. per policies approved by the consortium as well as any confidential information received by third party collaborators.
• Analyzing, publishing and/or publicly releasing and disseminating results, data and other products of the study in a timely manner, concordant with the approved plan for making quality-assured data and materials available to the scientific community and the NIH, consistent with NIH policies and goals of the NOFO.
• Sharing data, materials, informatics tools, methods, information and unique resources that are generated by the project as appropriate and in accordance with NIH policies in order to facilitate progress and consistent with achieving the goals of the MPS program.
• Participating in one "kickoff meeting" held at the beginning of the award period as an organizing workshop together with NIH and CASIS staff. This organizing workshop will go over Terms and Conditions of Award for the UG3/UH3, TC Consortium responsibilities and duties, and provide an opportunity for recipients to describe their project to the consortium.
• Attending and presenting findings at semi-annual NIH Tissue Chip Consortium meetings organized by the NIH, which should be factored in the budget proposal.
• Working with the members of TC Consortium to establish agreements that address the following issues: (1) procedures for data sharing among consortium members and data sharing with industry partners, as appropriate; (2) procedures for safeguarding confidential information, including without limitation, any data generated by the consortium as well as information and/or data received from external collaborators; (3) procedures for addressing ownership of intellectual property that result from aggregate multi-party data; (4) procedures for sharing biospecimens under an overarching MTA amongst consortium members that operationalizes material transfer in an efficient and expeditious manner as appropriate and consistent with achieving the goals of the program; (5) procedures for reviewing publications, determining authorship, and industry access to publications.
• Ensuring that for activities that involve academic and/or industry collaborations within and outside the TC Consortium there are appropriate research collaboration agreements (e.g., CRA, CDA, MTA etc.) with terms that ensure the collaboration is conducted in accordance with the Cooperative Agreement terms of award as well as any additional applicable NIH policies and procedures.
• Prior to initiation of the UH3 stage, providing an updated human subjects protection plan (e.g., protocol amendment, IRB approval of amendments to the protocol or consent form, etc.) and a detailed data and safety monitoring plan (DSMP) if appropriate, for approval by NIH.
• Upon completion or termination of the project, ensuring all study materials, tools, databases and procedures developed from the project are broadly available (e.g., putting into the public domain) or made accessible to the research community according to the NIH-approved plan submitted for each project, for making data and materials available to the scientific community and the NIH for the conduct of research. The data management and sharing plan should include a plan to accomplish this within 90 days of the end of the study.
• Coordinating efforts with other recipients, especially in circumstances where synergy of efforts and resources is beneficial to the overall goals of the MPS program.
• Coordinating or jointly publishing findings in a timely manner, and as to have the broadest impact.
• Ensuring all subjects are properly consented to allow appropriate sample and data distribution to researchers in academics and industry.

Publications

The PD(s)/PI(s) will be responsible for the timely submission of all abstracts, manuscripts and reviews (co)authored by project investigators and supported in whole or in part under this Cooperative Agreement. The PD(s)/PI(s) and Project Leaders are requested to submit manuscripts to the NIH Program Officer and Project Scientist(s) within two weeks of acceptance for publication so that an up-to-date summary of program accomplishments can be maintained. Publications and oral presentations of work conducted under this Cooperative Agreement are the responsibility of the PD(s)/PI(s) and appropriate Project Leaders and will require appropriate acknowledgement of NIH support. Timely publication of major findings is encouraged.

Communication Plans

The PD(s)/PI(s) will be responsible for:

• Participating in regular conference calls with NIH and CASIS staff.
• Participating and presenting findings at the semi-annual NIH TC Consortium meetings convened by the NIH.
• Coordinating or jointly publishing findings in a timely manner, and as to have the broadest impact.
• Making new information and materials known to the research community in a timely manner through publications, web announcements, reports to the NIH.
• Recipients will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NCATS will designate program staff, including a Program Officer to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the Notice of Award. The Program Officer will make the final determination on the negotiated milestones and will also make the final determination on whether the milestones are met.

NIH Project Scientist(s)

Project Scientists are members of the trans-NIH Microphysiological Systems Working Group that will have substantial scientific/programmatic involvement in the technical assistance, advice and coordination of this team; Project Scientist(s) will facilitate and not direct the activities of the team.

Specifically, Project Scientist(s) will be substantially involved in this project as follows:

• Facilitating interactions among awardees and CASIS participants.
• Monitoring milestone progress and help identify recourses if needed.
• Coordinating and facilitating the activities of the program, attending and participating in all meetings of the NIH TC Consortium.
• Working with members of the trans-NIH Microphysiological Systems Working Group to review the scientific progress and administrative accomplishments of the award recipients and review the project for compliance with operating policies and procedures, including meeting milestones. Based on this review, the Program Officer may recommend to the NIH to continue funding, or to withhold or restrict support for lack of progress or failure to adhere to NIH policies. Review of progress may include regular communications between the PD(s)/PI(s) and NIH staff, periodic site visits for discussions with research teams, fiscal review, and other relevant matters. The NIH retains the option of organizing periodic external review of progress.
• Preparing up-to-date summaries of program accomplishments based on manuscripts provided by the recipient within two weeks of acceptance for publication.
• Participating (with the other trans-NIH Microphysiological Systems Working Group members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols, project milestones or approaches as warranted.
• Serving as a liaison between the award recipients, the Advisory Councils for those Institutes that plan to administer elements of the NIH Tissue Chips program, and the larger scientific community.
• Coordinating the efforts of the recipient with others engaged in MPS research, including other recipients under this NOFO and those recipients involved in related NIH programs.
• Attending all trans-NIH Microphysiological Systems Working Group meetings and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action.
• Periodically reporting progress to the Directors of NIH Institutes/Centers/Offices involved in the NIH Tissue Chip program.
• Lending relevant expertise and overall knowledge of NIH-sponsored research to facilitate the selection of scientists not affiliated with the recipient institutions who are to serve as External Scientific Consultants, as needed.
• Maintaining public-private partnerships established under the NIH Tissue Chip program.
• Providing input into the design of research activities and play a key role in coordinating research efforts.
• Monitoring milestone progress and help identify recourses if needed.
• Ensuring that the awarded project(s) adhere to cooperative agreement data-sharing and other resource-sharing policies.
• Facilitating collaborations with, and access to, other NIH-supported research resources and services.
• Facilitating negotiations with companies interested in working with the award recipients.
• Providing advice on project management and technical performance.
• Coordinating and manage trans-NIH Microphysiological Systems Working Group efforts.
• Providing guidance to the recipients on private-public partnerships and regulatory agency policies.
• Inviting experts with relevant scientific expertise to provide feedback on TC program activities.
• Providing copies of all milestone documents and progress reports to CASIS as part of the MOU between NIH and CASIS.

The NIH will enlist additional scientific experts as necessary from within the NIH, other government agencies, whose function will be to advise the PD(s)/PI(s) in carrying out the goals and aims of the approved studies.

The NIH reserves the right to curtail or phase out the award in the event of (1) a substantial shortfall in accomplishing the management goals and responsibilities as stated in the reviewed application, (2) failure to meet procedures and milestones, and/or (3) substantive changes in the management of award(s) that are not in keeping with the objectives of the NOFO.

Areas of Joint Responsibility include:

• Collectively, award recipients and NIH staff will determine criteria and processes for quality control of information and data to be posted for the research community, consistent with NIH policies and achieving the goals of the program as described in this Notice of Funding Opportunity.
• Participate in recurring monthly meetings to discuss progress, obstacles and any other TC-related issues and/or activities.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between recipients and NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: 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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and HHS regulation 45 CFR Part 16.

3. Data Management and Sharing

Consistent with the 2023 NIH Policy for Data Management and Sharing, when data management and sharing is applicable to the award, recipients will be required to adhere to the Data Management and Sharing requirements as outlined in the NIH Grants Policy Statement. Upon the approval of a Data Management and Sharing Plan, it is required for recipients to implement the plan as described.

4. Reporting

When multiple years are involved, recipients will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement Section 8.4.1 Reporting. To learn more about post-award monitoring and reporting, see the NIH Grants & Funding website, see Post-Award Monitoring and Reporting.

A final RPPR, 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 Section 8.6 Closeout. NIH NOFOs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 2 CFR Part 200.301.

Section VII. Agency Contacts

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: https://www.era.nih.gov/need-help (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-480-7075

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Dmitriy Krepkiy, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Office of Special Initiatives
Phone: 301-451-2232
Email: [email protected]

Tiziana Cogliati, Ph.D.
National Institute on Aging (NIA)
Division of Aging Biology
Telephone: 240-397-4596
Email: [email protected] 

Marilyn Moore-Hoon, Ph.D.
National Center for Advancing Translational Sciences (NCATS)
Telephone: 301-827-9549
Email:[email protected] 

Tiangay Waines
National Center for Advancing Translational Sciences (NCATS)
Phone: 301-496-1132
Email: [email protected]

Jeni Smits
National Institute on Aging (NIA)
Telephone: 301-827-4020
Email: [email protected] 

Section VIII. Other Information

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 2 CFR Part 200.