Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
Office of Strategic Coordination (Common Fund)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative through the NIH Office of the NIH Director, Office of Strategic Coordination. The FOA will be administered by the National Institute of General Medical Sciences (NIGMS) on behalf of the NIH.
New
RFA-RM-19-009, U24 Resource-Related Research Projects – Cooperative Agreements
93.310
The purpose of this Common Fund initiative is to advance the application of cryoelectron tomography (cryoET), a powerful new method for directly visualizing macromolecular associations and organization in native cells. The two FOAs for this initiative will establish a national network of service centers that will provide these services to the community: collection of high-resolution cryoET data, cryoET specimen preparation, access for users to advanced instrumentation for cryoET, and cross-training in cryoET methods. This FOA will establish one service center that will serve as the network's central hub. The hub will serve user laboratories in the community directly and will also provide services to the four service centers that will be established by the companion FOA, RFA-RM-19-009. Those other centers will specialize in specimen preparation. The hub will perform cryoET data collection for all the user laboratories served by the whole network.
June 21, 2019
October 12 , 2019
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.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from NIH Guide for Grants and Contracts ).
Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions.
Applications that do not comply with these instructions may be delayed or not accepted for review.
Background
The purpose of this Common Fund initiative is to advance the application of cryoelectron tomography (cryoET), a powerful new method for directly visualizing macromolecular associations and organization in native cells. An earlier Common Fund FOA, RFA-RM-17-002, supported the establishment of three National Centers whose primary mission is the determination of the atomic structure of isolated molecules and complexes by cryoelectron microscopy (cryoEM). This new FOA and its companion FOA RFA-RM-19-009 aim to increase research capacity for cryoET of intact cells and tissues. The goal of this initiative is to provide nationwide access to advanced cryoET instrumentation and technical support, as well as to assist investigators in the development of skills needed for research using cryoET.
This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress. CryoEM and cryoET have been selected for Common Fund support because they open up previously inaccessible levels of biological organization to high-resolution structure analysis.
Recent technical advances in single-particle cryoEM have made it capable of generating reliable atomic models of complete and fully functional macromolecular complexes. An emerging related cryoEM method, cryoET, can image macromolecular assemblies in intact unstained frozen cells in three dimensions (3-D). Together, these methods enable high-resolution analysis of previously inaccessible levels of biological organization, ranging from below 100kD to whole cells.
Traditionally, macromolecular structure determination has been limited to the analysis of isolated molecules and structures. CryoET has the unique ability to visualize macromolecular organization in native cells; it utilizes the intrinsic contrast of frozen cellular material to directly image macromolecules. Recent advances in sample preparation, electron optics, detectors and image processing have made it possible to define the architecture of macromolecular complexes within intact cells, and proof of practice has been shown for the targeting of specific low copy number features in intact tissues for cryoET. It is anticipated that these methods will be combined by developers into complete workflows in the coming years, and that cryoET will then have a transformational impact on fundamental biomedical research.
The high costs of microscopes and supporting instrumentation for specimen preparation have been barriers to the development and utilization of cryoET. This initiative will establish a national network of service centers to provide access to this new technology.
Research Objectives
This initiative will establish a national network of service centers to provide nationwide access to cryoET technology. The two FOAs for the initiative will support a network having two kinds of service center. This FOA will establish one larger service center that will serve as the network's central hub. The hub will provide cryoET services to two constituencies. First, it will serve user laboratories in the community directly. Second, the hub will also provide services to the four service centers that will be established by the companion FOA, RFA-RM-19-009. Those other centers will specialize in specimen preparation. The hub will perform cryoET data collection for all the user laboratories served by the whole network. The activities of all the centers in the network will be coordinated by a Network Coordinating Group, a committee comprising the PD(s)/PI(s) of all the centers and NIH staff.
The hub established by this FOA will provide the following services to the research community directly: (a) collect high-resolution cryoET data for all the user laboratories served by the network; (b) perform standard cryoET sample preparation services for user laboratories; (c) provide access for users to advanced instrumentation for cryoET; and (d) provide cross-training to user laboratories in specimen preparation methods, instrumentation, and cryoET data collection. In support of these service objectives, the hub is expected to update its standard services on a continuing basis by performing internal technology development.
In addition to providing services directly to user laboratories, the hub will also provide support services to the other centers in the network. The hub and the other centers will coordinate on the shipping of specimens to the hub for data collection. In cases where finished specimens are too fragile to be shipped, the hub and the other centers will coordinate on the completion of specimen processing at the hub before data collection. At the direction of the Network Coordinating Group, the hub will provide data collection services needed for the internal technology development activities of the other centers in the network. The hub will provide administrative and logistical support for the Network Coordinating Group and its activities, including scheduling and organizing meetings, the user application and review processes, the allocation of services between centers, and record keeping.
Scientific scope. The scope of this cryoET initiative is limited to analysis of native, frozen-hydrated specimens using 3-D (tomographic) transmission electron microscopy. Other emerging technologies, for example those using embedded specimens and/or scanning electron microscopy, are also important, but are outside the scope of the initiative.
Samples from subcellular to tissue levels are eligible for services. Services and access for outside user laboratories to develop cryoET methods and technology will also be supported. An explicit objective of this initiative is to expand the cryoET research base by assisting laboratories that are new to cryoET to establish themselves in the field.
Although software and computation are also essential aspects of the cryoET workflow, these aspects are not targeted for support by these FOAs. Investigators should support these activities through existing NIH grant programs or other funding sources.
User Services
(a) CryoET data collection. The hub will collect cryoET data and provide basic computational services for all the network's users. The network will also allocate microscope time at the hub for the internal technology development work of the other centers in the network.
(b) Specimen preparation. The hub's technical staff will prepare specimens for user laboratories using standard protocols that the hub has established. For specimens that must be worked up on site, the hub will provide wet lab facilities for biochemistry and handling cells and tissues. The hub's staff will advise and support users in the use of these supporting facilities. The hub will complete specimen preparation for the other centers when the specimens are too delicate to be shipped in a finished state.
If a specimen cannot be prepared with the hub's standard procedures after the normal allotment of time and effort, work on the specimen as a user service should be ended. The hub should advise the user on pursuing the work independently and/or enlisting an expert collaborator. The user may apply for cross-training to acquire the basic skills needed to independently develop a process customized for the specimen. Alternatively, in special cases where the hub deems continued work important for advancing its capabilities for its service mission, it may choose to conduct the work collaboratively as an internal technology development activity, rather than as a user service.
(c) Access to instrumentation. The hub will provide access to advanced instrumentation for user laboratories that are developing or applying their own methods to prepare specimens for cryoET. The hub's technical staff will supervise the instruments and assist these users. For user-directed specimen preparation, hub personnel will operate equipment under the direction of users. The staff should work effectively with users to execute their custom or experimental specimen preparation procedures. Provisions should be made for users to participate remotely to supervise and direct complex workflows, including live close-up video.
(d) Cross-training. The hub will offer cross-training (instruction in the theory and practice of equipment and methods, and hands-on training in their use) to user laboratories. This should cover the basic skills laboratories need to undertake their own independent cryoET research and may include specimen preparation, microscopy and data collection, and basic computation (image correction, alignment, and reconstruction). In addition, the hub will prepare and disseminate technical documentation and protocols and engage in outreach activities to assist outside laboratories in adopting cryoET methods. For complex procedures, comprehensive documentation (including close-up video) should be made available to the public.
Facilities. The hub will acquire a dedicated cryoelectron microscope configured for high-resolution cryoET data collection. It is anticipated that, during the project period, the state of the art in specimen preparation for cryoET will advance to the analysis of intact tissues. The hub and the other centers in the network are expected to keep abreast of these advances where practicable, and to implement them as new services when they can be performed reliably and reproducibly. Therefore, the hub, like the other centers in the network, should equip itself for handling of cells and tissues, plunge and high-pressure freezing, correlative light and electron microscopy (CLEM), cryo-sectioning, and focused ion beam (FIB) milling, and make these available to user laboratories.
Operations. The hub and the other centers in the network are expected to coordinate with each other to deliver uniform services to the community and to keep pace with new advances in practice. The hub should budget for time and travel throughout the project period for its staff to visit outside developers' laboratories and the other centers to learn new methods. The hub and the other centers may also individually and jointly engage external consultants.
The hub's operations and communication should be designed to optimize returns from the users' investment of time and materials. The staff will work with users from the beginning of the application process to ensure that samples are ready for processing. The hub's personnel will provide technical support as needed to maximize throughput and efficiency, and to optimize the quality and quantity of specimens. This includes not only technically optimal and reliable performance of the environment and instrumentation, but also staff attention and support for users. Staff and operations should be organized to ensure seamless interfacing between users and the hub's facilities and services.
Operating procedures should be designed to minimize miscommunication, equipment outages, technical incompatibilities, and other avoidable interruptions. The hub should interface effectively with vendors for service arrangements that minimize instrument downtime. The hub should be equipped and operated to minimize impact of instrument outages and other service interruptions, especially when users have travelled to the site.
Instrumentation. The hub's technical staff will supervise the use of equipment. At its discretion, the hub may choose to qualify some users to perform some operations. The staff will assist users as needed with the operation of equipment.
Computation. The hub will perform standard initial processing and correction of raw image data and standard calculation of tomographic density maps if requested by users, but will not perform specialized computation. The hub should make provisions for short-term storage and efficient transfer of users' cryoET data, but users are responsible for their own long-term data storage. In addition to managing cryoET data for the users, the hub will provide logistical support for data exchange between the centers in the network (e.g. using cloud services).
Internal Development Activities
Internal development comprises the activities that the hub will perform to implement user services. In support of their service mission, all the centers in the network, including the hub, are expected to keep pace with advances in practice by implementing new protocols into their workflows. As they become practicable, the network will implement progressively more advanced standard services. The hub should equip itself and train its staff to keep pace with the development of new methods of cryoET specimen preparation and data collection.
The hub, like the other centers, will develop outside developers' protocols into robust and reproducible workflows and implement them as standard services. Internal technology development should emphasize the advancement of services to be offered during the project period. Hence, special attention should be directed to protocols that have been developed elsewhere and are known to work. The hub's staff may author publications on technical advances accomplished on their hub appointments. The hub may engage in collaborations as part of its internal technology development.
The hub, like the other centers, is expected to maintain a balance of investment between providing existing services and keeping up to date in their capabilities by adding new services. During their setup period, it is expected that the hub and the other centers will need to reserve more effort to training their staff and implementing protocols for specimen preparation. After setup, the preponderance of effort should be on delivering services.
Scope of Services
User Services. The goals of this initiative are catalytic, that is, to enable user laboratories to perform their own research rather than to perform it for them. When delivering services, the scope of the hub's involvement in users' research should be limited to standard services.
If a user's specimen is too challenging to prepare with standard services, there are several options. The user may apply for access to the hub's instrumentation and pursue the project independently, perhaps with an expert collaborator. Alternatively, if continuing the work as a pilot project will advance the hub's capabilities for its service mission, the hub may choose to pursue it as an internal development activity, which is not a user service. Finally, hub staff members working on outside appointments (i.e., effort supported by other funding sources) are free to collaborate with the user, but any such work must be pursued as an externally-supported outside research project, not as a hub-supported user service.
Cross-training. Again, the intent is catalytic, that is, to help user laboratories acquire basic skills and prepare for independent research, rather than to engage in research collaboration. The hub should cross-train as many new laboratories as is practical while maintaining high standards. Thus, it should strike the correct balance between providing an adequate instruction in the basics relevant to the user's needs without being drawn into a collaborative role in the research. After completing their cross-training experience, users should be able to advance on their own to research independence.
The hub should complete cross-training and transition new users to independent research in a timely manner. To assist their transition from assistance to independence, the hub may offer guidance about opportunities for research collaborations with experts outside the hub. The NIH will regularly review the progression of user laboratories through cross-training to independence.
Allocation of Services
The hub's services and cross-training should be provided and tracked on a parent laboratory basis. That is, they should be provided to independent laboratories, rather than to individuals within laboratories.
The Network Coordinating Group will run a Joint User Review Committee for scientific and technical review of requests for services . The Network Coordinating Group will jointly allocate approved applications for services among the hub and the other centers in the network. All the centers, including the hub, will offer the same set of basic standard services and access to advanced instrumentation, but each individual center will decide what additional standard services to offer. The centers will coordinate on technology transfer to assist each other in implementing progressively more advanced services. The hub will provide administrative and logistical support (for example, organizing conferences, reviews, and keeping records) for the activities of both the Network Coordinating Group and the Joint User Review Committee.
The network will offer equal-opportunity access to services through a nationwide, open application process. The priority is to serve a broad and diverse range of users and institutions. Access will be prioritized by a formal process of evaluation by the Network's Joint User Review Committee and programmatic and administrative review by the Network Coordinating Group. As demand for services develops to exceed capacity, the network should institute transparent review criteria and the hub and the other centers should apply them consistently in prioritizing access to services. In allocating its resources and services, each individual center should balance considerations of providing enough time and support for users to get their work done against the strategic goal of making services as widely available as is practical.
Application process. Access to the network's facilities and services will be allocated nationwide solely in accordance with a formal application process. There will be a single public application track for all users, including local users. With the exception of the hub's own internal technology development and evaluation projects, other local use must be reviewed and prioritized through the same public channels as all other users, including use of unassigned or idle capacity.
User review. After the cryoET network grants have been awarded, the Network Coordinating Group will appoint the Joint User Review Committee evaluation of requests for services . Names of potential members of this committee (and any other committees) should not be included in the hub application, nor should they be contacted prior to the completion of the review process.
Evaluation for all services will be designed and overseen by the Network Coordinating Group and performed by the Joint User Review Committee. It will consider scientific rationale, the suitability and status of the specimen, technical feasibility, provisions for interpretation and downstream computation on tomograms, and the effort and resources needed to provide the service. For non-expert applicants, this review should examine supporting collaborative arrangements. The user review process should be informed by and consistent with the objectives of this FOA.
Administrative review and allocation of applications. After evaluation by the Network's Joint User Review Committee, the Network Coordinating Group will prioritize the applications and assign approved service projects to the centers, taking into consideration applicants' preferences and the individual centers' capabilities. Administrative review by the Network Coordinating Group should consider the breadth and diversity of supported users and institutions, the breadth and diversity of supported research topics, provision of sufficient access for users to complete their work or cross-training, and other resources available to applicants. The hub will provide administrative and logistical support and keep records for the administrative review and allocation of services by the Network Coordinating Group.
Scheduling of services. The individual centers will internally allocate their staff time and resources for external user services, internal technology development, and maintenance. As far as is possible, the assignment of projects to centers and the scheduling of services by centers should optimize travel and lodging for users.
Outside projects of hub staff. When they are not working on their hub appointments, part-time staff members working on outside projects are eligible to apply to the network for services as outside users. These projects should be reviewed and approved through the same channels as other outside users' requests, after which the hub may allocate services (e.g., time on instruments).
General
Dissemination, outreach, information sharing. Individually and collectively, the hub and the other centers in the network are expected to carry out activities to inform the scientific community about their capabilities and services, to promote broader application of cryoET, and to actively recruit users. The hub should have a website which provides up-to-date and complete information about facilities and services, policies, and the application process. The hub's instructional materials and protocols should be posted on the website. The hub and the other centers may individually and/or jointly engage in outreach activities like workshops to efficiently promote the adoption and application of cryoET methods.
Consultants, subawards. The hub will have the authority to rebudget and to set up and discontinue activities that are within the approved scientific scope of this FOA, for example to hire consultants or to contract out work. The hub is expected to exercise flexibility (within the approved scientific scope) in engaging consultants in response to changing needs and unexpected opportunities.
Partnerships. The hub and the other centers may individually and/or jointly form partnerships that advance their service mission. Examples include but are not limited to collaboration with academic researchers and technology developers, and partnerships with manufacturers/vendors of instrumentation.
Facility charges. There will be no charges to users for non-profit use.
User accommodation. Convenient lodging, meals, and transportation must be available to users at reasonable cost.
Record keeping. The network and the centers will operate a Records Management System (RMS) to (i) track the delivery of services to external user laboratories, and (ii) track all instrument use (service, internal, maintenance). The grantees and NIH will use this information for ongoing evaluation and planning. The information to be included in the RMS is detailed in Section VI (Cooperative Agreement Terms and Conditions of Award). The hub will provide administrative and logistical support for record keeping to the other centers in the network.
Staff. As specified in Section III.1 (Eligible Individuals, Program Director/Principal Investigator) the PD(s)/PI(s) must include one or more individuals with expertise in high-resolution cryoEM (but not necessarily in cryoET).
The hub will provide support for its staff to visit developers' laboratories and acquire expertise with methods, especially in the initial phases of the project when the hub is equipping itself and establishing protocols. Since the network is expected to offer more services as the field advances, the staff should be training in new methods on a continuing basis throughout the project period. The hub may engage consultants and support collaborations through subcontracts.
To attract and retain highly-qualified technical service professionals, the hub is encouraged to develop strategies for the recruitment, training, and development of staff and to set their salaries commensurate with their experience and expertise.
Outside research. Hub personnel on part-time appointments may participate in outside research, provided their effort on this research is supported by other funding sources. This external research should be kept financially separate from the hub's activities. As is specified in the subsection on Allocation of Services, hub staff must apply as outside users through the network's public application process for use of the hub's facilities for their outside research.
Authorship. The hub's personnel should not be co-authors on users' publications for standard services and cross-training that they deliver as hub employees. Requirements related to this restriction are specified in Section VI. Cooperative Agreement Terms and Conditions of Award (Special Requirements). The expert technical assistance of the staff may be credited by name in the acknowledgements section of users' publications. This restriction applies only to user services; as is noted elsewhere in this section, the hub's personnel may engage in collaborative technology development projects and publish with outside laboratories as part of the hub's internal technology development activities.
Resource and data sharing. Research receiving services from the hub is NIH-supported research and is subject to all NIH policies. Users must agree to follow all applicable NIH policies for the sharing of their data and research resources when they apply for services. Services may not be provided for research whose publication and sharing may be subject to any trade or other secrecy restrictions. Services may be provided to for-profit entities that intend to publish their results and share their research data in accordance with NIH policies.
Vertebrate animals and human subjects. All research receiving services from the hub that, according to NIH's definitions, involves human subjects or vertebrate animals must have the requisite NIH approvals. If the research is supported by an NIH grant, the user must include documentation of NIH approvals for the research when applying for services. At its discretion, the Network Coordinating Group may decide whether or not to support research that involves human subjects or vertebrate animals that is not NIH-supported. If the hub supports vertebrate animal or human subjects research that does not already have an NIH approval, it must obtain all the requisite NIH approvals before initiating any work.
Advisory committees. Although the hub and the other centers may individually and/or collectively utilize an Advisory Committee, this is optional, and such a committee would not involve NIH. An Advisory Committee should not be used in lieu of the PD(s)/PI(s) for project management. The names of potential members of an Advisory Committee (or any other committee) should not be included in the application, nor should they be contacted prior to the completion of the review process.
Network Coordinating Group. The hub and the other centers funded through this initiative will participate with NIH staff in a Network Coordinating Group to share information and arrange for mutual assistance between centers. This group will design and run the user application and evaluation process, and will allocate all network services for approved projects, including data collection and data management services at the network hub. The Network Coordinating Group will organize an annual meeting of the PD(s)/PI(s) and key staff of all the cryoET centers in the network. The hub will provide the administrative and logistical support for this meeting.
Term of support, interim review. Six years of support may be requested. The initial project period (phase 1) will be four years. Near the end of the third year, an administrative review will be conducted to assess progress on the project. If progress is deemed adequate and additional funding is warranted, the project will be eligible for phase 2 support, the final two years of funding.
FAQ. A list of frequently asked questions for this FOA is posted at https://commonfund.nih.gov/cryoem/FAQ. In addition, because this FOA has restricted objectives and special application instructions, review criteria, and Terms and Conditions of Award, potential applicants are strongly advised to discuss their plans with the Scientific/Research contact listed in Section VII below.Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
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The NIH Common Fund intends to commit approximately $7,175,000 in FY 2020 to fund 1 award.
The maximum yearly budgets (total costs) are
$7,175,000 for year 1,
$7,175,000 for year 2,
$1,175,000 for year 3,
$1,175,000 for year 4,
$1,175,000 for year 5, and
$1,175,000 for year 6.
Applicants may request a maximum of six years of support. The initial project period (phase 1) is four years. An additional two years of support (phase 2) may be granted contingent upon the outcome of an administrative review of progress.
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
For-Profit Organizations
Governments
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
The PD(s)/PI(s) must include one or more individuals with expertise in high-resolution cryoEM (but not necessarily in cryoET). That is, skills and knowledge of cryoEM are necessary for the team to be eligible. However, it is not required that every PD/PI be a cryoEM expert. Because few investigators have had experience with CLEM and FIB, prior experience with these methods is not required.
Individuals may be a PD/PI on only one application to this FOA. Individuals may apply to both this FOA and to its companion FOA, RFA-RM-19-009, but only one of these applications will be awarded.This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
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:
Paula Flicker, Ph.D.
Email: [email protected]
Note the following additional instructions:
Facilities & Other Resources: Describe both existing and planned facilities and other resources. If they do not yet exist, describe the specifications that will be met. This section should explicitly indicate whether all the vendors' environmental specifications for microscopes, other instrumentation, and computers will be met. These include but are not limited to temperature, humidity, electric and magnetic fields, vibration, and electrical power. Describe the specifications that will be met for climate control in the microscope and specimen preparation areas, including the temperature and humidity ranges that will be maintained. Specifically address the adequacy of the climate control for the transfer of specimens that are sensitive to humidity.
Describe the laboratory facilities that will be available to visiting users for biochemistry, handling of cells and tissues, cryoET specimen grid preparation, and computation. Indicate the distances between the facilities comprising the hub. Diagrams of the planned layout and relative locations of facilities may be included.
Describe local accommodations for out-of-town users, including the availability, proximity, and costs of lodging, meals, and local transportation.
Describe local scientific and technical expertise and intellectual resources, including laboratories engaged in high-resolution cryoEM research and/or technical development.
Note the following additional instructions:
PD(s)/PI(s): At least one PD/PI must be an expert in high-resolution cryoEM (but not necessarily in cryoET). The team should document its qualifications for any supporting methods proposed in the application, for example the handling of cells and tissues and fluorescence microscopy.
Biosketches of the PD(s)/PI(s) should include their qualifications and experience in cryoEM (which may or may not include cryoET). They may include documentation of (a) an active research program in cryoEM, (b) leadership in solving challenging research problems in cryoEM and in other fields, (c) technical innovation in carrying cryoEM analyses through to publication, (d) experience in acquiring, maintaining, and operating state-of-the art cryoEM and/or other instrumentation, including troubleshooting instrumental, environmental and other technical problems, (e) experience participating in or organizing collaborative research efforts and/or managing a resource, experience providing services for their institution or the community at large, and (f) skills in recruitment, management, and negotiation. Qualified individuals who do not hold academic appointments, for example, a facility director/manager, may serve as PD(s)/PI(s).
Individuals who have PD/PI-level responsibilities and authority, or who bring required expertise to the leadership team, should have a PD/PI role in the project. The application should not include position descriptors like "Co-PI", "Co-investigator", "Co-director", or variations on these titles that imply a PD/PI-like role. Titles like Facility Director or Manager are acceptable for persons who will direct day-to-day operations but will not have a PD/PI role.
Scientific and technical staff: It is not expected that scientific staff will already be identified; "To-Be-Named" is acceptable.
The key personnel should include only individuals who have a direct and specific role in the hub that is described in the application. Names of potential committee members or other advisors should not be included in the application, nor should they be contacted before the review process is complete. Potential users should not be identified in the application.
All instructions in the SF424 (R&R) Application Guide must be followed.
Note the following additional instructions:
The budget justification should address both phase 1 (years 1-4) and phase 2 (years 5-6) of the project. While a 10-year R&R Detailed Budget form is provided in the application package, applicants may not request more than 6 years of support.
Senior/Key Personnel: For each staff position, describe the technical responsibilities. The required PD/PI who is expert in cryoEM must devote a minimum of three person-months' effort to the hub; only one PD/PI is subject to this minimum requirement. If this PD/PI directs an existing center funded under RFA-RM-17-002, a minimum of one person-month effort on this project is acceptable.
Equipment Description: The budget justification section should include an evaluation of alternative instruments or manufacturers and should explain the use of all major equipment items. Provide descriptions and costs of equipment items, but do not include detailed price quotations from vendors in the application. Service Contracts are allowed. The maximum yearly budgets for years 1 and 2 specified in Section II, Award Information, Award Budget, include provision for equipment and extended service contracts.
Travel: Travel and other costs for personnel and consultants (including User Review and Advisory Committee members) are permitted. These may include travel to committee meetings, scientific meetings, and for information sharing activities. The budget should also include funds for the PD(s)/PI(s) and key staff members to attend two meetings: (a) an annual meeting of the cryoET network, and (b) an annual meeting of all the projects supported by the Common Fund CryoEM and CryoET initiatives.
Cost of living escalation should not be included in any cost categories.
Alteration and Renovation costs are not allowed.
The research plan should include both phase 1 (years 1-4) and phase 2 (years (5-6) of the project.
Specific Aims: The Specific Aims should address the objectives described in Section I and should not include other research.
Research Strategy: The Research Strategy should address the objectives described in Section I and should not include other research. The following should be addressed in the Research Strategy:
Infrastructure and technical operations. Describe how the hub will be equipped. Describe how the instruments will be maintained and operated to achieve state-of-the-art performance. Include standards and procedures for maintaining microscopes, specimen preparation equipment, other instruments, environmental conditions, and software. Describe intellectual resources available to assist in troubleshooting problems.
Staffing. Together, the Budget Justification and Research Strategy should explain the qualifications and roles for each staff position. Describe how well-qualified staff will be recruited, trained, and retained.
Training and continuing education of staff. Explain how staff will be trained initially and how they will be kept current with new methods from outside developers' laboratories. If the PD(s)/PI(s) do not have prior experience with cryoET data collection, the application should include plans for them to acquire these skills. If the PD(s)/PI(s) do not have prior experience with methods that they propose to apply, for example, CLEM, FIB, and other specimen preparation methods, the application should include plans for them to acquire the necessary skills.
Services. Describe the kinds of specimen preparation that will be offered as standard services during the project period. Explain how specimens will be evaluated after preparation. Assess the technical challenges and estimate the staff effort and resources needed to deliver the different services. Include timelines for implementing services. Describe how the delivery of all services will be managed and how the FOA's objectives for quality of user services will be met, including communication with users and scheduling.
Describe coordination with the other centers on the shipping of specimens to the hub for data collection and, in cases where finished specimens cannot be shipped, on the completion of specimen processing at the hub before data collection.
Describe data collection, image correction, and computation of tomograms. Justify the adequacy of computational resources for the expected production of data. Describe the categories and extent of computational support for users. Discuss the handling (volume, storage, disposal schedules) of raw high-throughput data. Describe the transfer of data collected by the hub to users.
Capacity and workflow. Describe the capacity (throughput) of the hub for specimen preparation and screening, data collection, and computation. Describe the deployment of staff and instruments in multiple simultaneous workflows. Indicate how workflows will be adjusted in response to demand. Explain how effort on specimen preparation, data collection, and data analysis will be coordinated internally and with the other centers to maximize efficiency.
Access. Describe how user access to instrumentation, including FIB, will be handled for users who can direct their own procedures. Describe support for remote access to instrumentation (including specimen preparation), including provisions for video.
Cross-training. Describe the principles, strategies, and management of cross-training and technology transfer to user laboratories. Explain the management of space, facilities, and assistance for visitors.
Implementation of new services. Explain how the hub will identify new methods and evaluate their readiness for adoption as new services. Explain how developers' protocols will be developed into robust and reproducible workflows and implemented as services. Assess the technical challenges and estimate the staff effort and resources needed to establish (implement) the different services.
Consultants, collaborators, subcontracts. Describe arrangements with, and include letters of support from, consultants and/or collaborators who have been engaged and have a specific role in the project that is described in the application. However, do not include the names of persons who are potential consultants but do not yet have a specific role in the project that is described in the application. Describe general strategies for selecting and utilizing consultants and collaborators.
The cryoET field is advancing rapidly and considerable time will elapse between preparation of an application and the start of the project period. Therefore, it is not required (or advised) that applicants engage in advance all the consultants who may be needed during the project period. It is not required (or advised) that subcontracts be formalized before the project has started and the center has had an opportunity to assess its needs. Rather, describe how the hub will exercise flexibility in engaging consultants in response to changing needs and unexpected opportunities.
Record keeping. Describe how information about the delivery of services will be recorded in a Records Management System and made accessible for review by NIH. Describe how follow-up information about outcomes will be obtained and made accessible. Describe how user feedback will be obtained and utilized in evaluation and planning.
User application process. After awards are made, the Network Coordinating Group will jointly design the user evaluation process and appoint the Joint User Review Committee. Do not include plans for this process or committee. Instead, describe the scientific and technical criteria that would be appropriate for evaluating user applications for cryoET services. Do not address administrative criteria. Names of potential members of the Joint User Review Committee (and any other committees) should not be included in the application, nor should they be contacted prior to the completion of the NIH peer review process.
Outreach. Describe the plans for informing the community about the hub's services, promoting the wider application of cryoET, and recruiting users; describe the website that will be developed.
Backup plans. Extended outages of facilities can unpredictably occur from fire, flood, earthquakes, accidents, theft, catastrophic equipment breakdowns, and other causes. The application should include plans for contingencies in which the facility is unable to perform its functions for an extended period (months or longer). They should include provisions for support (for example, alternative employment) of personnel if they are unable to work on the project for an extended period. Institutional support in terms of backup and/or special insurance is an option, as are reciprocal arrangements with other centers.
Advisory committee. An advisory committee is optional, but, if one is proposed, describe its functions. However, the names of potential members of this committee (and any other committees) should not be included in the application, nor should they be contacted prior to the completion of the review process.
Multiple PD/PI Leadership Plan (if applicable): The sharing of management responsibilities by a team of PD(s)/PI(s), rather than a single PD/PI, poses challenges for direction and management. It is important that the applicants devise a robust and workable management scheme and describe it clearly and completely. Useful guidance for management of projects by multiple investigators is posted on the NIH Multiple PD/PI webpages. Potential applicants are encouraged to consult the Institute Scientific/Research contacts listed in Section VII about their project management plans.
Letters of Support: Letters of support should be limited to: (i) persons who are named in the application and have a role in the project that is described in the application, for example expert consultants; and (ii) statements of commitment from institutional officials. Statements of commitment from institutional officials should describe the extent of availability of facilities and services (percent time and effort) committed to the project. Do not include letters from other persons who do not have a specific role in the project that is described in the application.The following modifications also apply:
All applications, regardless of the amount of direct costs requested for any one year, are expected to include a Data Sharing Plan.
The Resource Sharing Plan should describe the resources and data sharing agreement with users that the hub will require as a condition of access to services. This agreement should include a commitment by users to share resources and data generated with the hub's support in accordance with all applicable NIH policies and guidance.
Resources. Describe the major categories of resources likely to be produced and the plans for sharing them, as appropriate. Resources include complete protocols and instructional materials. Where applicable, the plan should specifically address computer algorithms, and software (including source code).
Data. Describe the categories of data that users will be expected to deposit in public databases, and categories of data for which public databases are not available. Include maps and structures that users eventually derive from analysis of specimens prepared and/or analyzed by the hub.Do not use the Appendix to circumvent page limits.
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.
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.
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.
Important reminders:
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 Division of Program Coordination, Planning and Strategic Initiatives, Office of Strategic Coordination, NIH (Common Fund), NIH. Applications that are incomplete, non-compliant and/or non-responsive will not be reviewed.
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 review criteria should be applied in the context of the objective of equal opportunity nationwide access to state-of-the-art services, equipment, methods, technical support, and cross-training as described in Section I (Funding Opportunity Description). For all the criteria, emphasis should be on the delivery of quality services and technical outcomes for users, and not on specific users or research that will be accommodated. Since strategies will need to be adapted with experience and changing circumstances, review emphasis should be on the resourcefulness of the investigators and the principles behind their strategies to acquire the necessary skills and deliver the services to users that they propose in their application.
Methods for cryoET specimen preparation are still under development, and there are very few investigators currently active in this research area. It is expected that many talented applicant teams may not have experience with the recently developed methods and instrumentation for specimen preparation that the hub will host. Further, many of the current methods for cryoET specimen preparation are likely to be superseded by new approaches in the near future. Therefore, the resourcefulness of applicants and their ability to learn on the job and master new methods will be more important over the long term than their current specific skill sets and experience. In evaluating applicants' qualifications, it is important to identify those applicants who are the most likely to successfully identify and creatively exploit future technological opportunities. Note that applicants were advised to describe how they will utilize collaborators and consultants, rather than to recruit them in advance of applying.Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the proposed hub address the needs of the research community that it will serve? Is the scope of activities proposed for the hub appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research community?
How well will the proposed hub meet this FOA's objectives of nationwide access to state-of-the-art services, equipment, cross-training, and technical support? How effective will the hub be in assisting outside laboratories in developing cryoET skills?
Are the PD(s)/PI(s) and other personnel well suited to their roles in the hub? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing cryoEM research? Do the investigators demonstrate significant experience with coordinating collaborative basic research? If the hub is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the hub?
Do the PD(s)/PI(s) have a record of solving challenging technical problems in cryoEM (which may or may not include cryoET)? Do they have a record of mastering new methods (in any field)? Do the quality and breadth of the PD(s)/PI(s)' publication records indicate that they will be able to provide well-informed, high-quality research guidance to new users in cryoET specimen preparation and microscopy? Will the PD(s)/PI(s) be able to fill their assigned roles and be resourceful enough to solve the kinds of problems expected to arise in the course of operations? Do they have skills in recruitment and management of personnel? Will they be able to attract highly-qualified applicants for staff positions?
Do the PD(s)/PI(s) have experience organizing or participating in collaborative research efforts and/or facility management? Do they have a history of performing services for their institution or for the scientific community at large? Will they be well-suited to running a service facility whose mission is limited to service and guidance of outside users?
Where applicable, are the concepts and strategies novel?
Does the application include creative strategies for the hub's staff to master new methods of specimen preparation with which they do not have prior experience? Are there innovative general principles for drawing on outside expertise and resources to help solve problems and improve procedures? Does the application include original strategies for assisting new users in the development of cryoET skills? Does the application include novel insights and approaches for the recruitment and retention of qualified staff and achieving and maintaining state-of-the-art capabilities and service?
Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of serving the research community and the cryoET network? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the services proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is new, does the proposed strategy adequately establish feasibility and manage the risks associated with developing the resource? Are an appropriate plan for work-flow and a reasonable timeline proposed?
Is the approach appropriate to accomplish the objective of equal opportunity nationwide access to state-of-the-art services, equipment, technical support, and cross-training? Does the research strategy adequately address administrative and technical issues and challenges? Will the hub be a leader in expanding the application of cryoET?
Is the approach flexible and adaptable to changing circumstances and technological change? Are the plans and resources devoted to initial self-training and the continuing education of the PD(s)/PI(s) and staff sufficient to establish the needed expertise in cryoET? Are there adequate plans for keeping the PD(s)/PI(s) and staff current with new cryoET methods emerging from developers' laboratories?
Are the principles and strategies for utilizing consultants and collaborations sound, and are they flexible enough to respond to changing needs and unexpected opportunities?
Multiple PD/PI Leadership Plan (if applicable). If there are multiple PD(s)/PI(s), are they integrated into an effective team? Will the Multiple PD/PI Leadership Plan provide effective scientific direction? Is a robust framework for making decisions proposed? Are sound principles for scientific and budgetary decision making set forth? Have the applicants anticipated and addressed management issues and problems that may arise during the course of the project?
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 institutional environment in which the hub will operate contribute to the probability of success in accomplishing the goals of serving the research community and the cryoET network? Are the institutional support, equipment and other physical resources available to the investigators adequate? Will the hub benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
For facilities and other resources that do not yet exist, will the plans for the site and environmental controls meet vendor specifications? Are institutional commitments clear? For existing facilities, will they meet specifications? If the hub relies on existing facilities, are they fully committed to the use of the hub? Will climate control for the specimen preparation areas be adequate?
Are accommodations for users (lodging, meals, local travel, office and storage space, computer access) adequate and reasonably priced?
Are wet labs, cell and tissue facilities, and specimen preparation facilities adequate for users who must prepare their specimens at the hub? Are the workspaces comprising the facility adequate and in close proximity to each other?
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.
Not Applicable
Not Applicable
Not Applicable
Not Applicable
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 NIH 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.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National General Medical Sciences Advisory Council 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 as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
• The PD(s)/PI(s) will manage the project and have authority over the project's budget. The PD(s)/PI(s) will direct the project in accordance with objectives of the FOA, the Terms and Conditions of the award, and other agreements with NIH. They should hold at least two official business meetings yearly. These may be telephone conferences.
• The PD(s)/PI(s) will operate a records management system (RMS) as described in Section I, FOA Description, Record Keeping to (i) track the delivery of services to external user laboratories and to the other centers in the network, and (ii) track all instrument use (service, internal, maintenance). The grantees and NIH will use this information for ongoing evaluation and planning. The RMS will include users, applications, reviews, and project information, staff support activities, outcomes, and user feedback. The RMS should be kept current and accessible for review at all times by NIH; periodic reviews of these records will be conducted at the regular business meetings. The RMS should include: (a) Applications and Review. Applications received, review evaluations, approved projects, project information, and outcomes. (b) User base. Laboratories and their participating persons served (including all the labs in a collaboration). Breakout of approved service projects, visits (in person, remote, mail-in), persons visiting, services provided, staff support and instrument time allocated. (c) User services. Breakouts by project of staff time devoted to user services (advice/support/instruction, sample assessment, specimen preparation and evaluation, data collection and computation) and other services (pre-application advice, outreach, workshops). (d) Major Instrumentation. Log of hours and outcomes for user services by project, type, maintenance, other, idle. Wait times and backlog. (e) Cross-training. Staff effort and resources devoted to cross-training and research guidance to user laboratories. Breakout of laboratories and their participating individuals, dates, hours, topics (sample evaluation, specimen preparation, microscopy, computation). Progression and outcomes of cross-training (for example, follow-up visits as users). (f) Research outcomes of user services. Biological topics/samples, unique specimens. Publications. EMDB and PDB deposition numbers for all publications supported. Funding sources and grant numbers for all hub-supported projects. This hub will provide administrative and logistical support for record keeping to the other centers in the network.
• The hub's research services and cross-training should be provided and tracked on a parent laboratory basis. That is, they should be provided to independent laboratories, rather than to individuals within laboratories.
• In accordance with the objectives in Section I. Funding Opportunity Description, the PD(s)/PI(s) will maintain a clear separation between the hub and local research activities, and ensure that all access to the hub's services is strictly on a single track, equal-opportunity, nationwide basis.
• All research publications supported by this project must acknowledge its support by citing the grant number in the form "supported by NIH grant U24 RM123456". The PD(s)/PI(s) should maintain a current listing of all publications supported by the hub, which includes the exact acknowledgement of support that appears in the paper. This list should also explain the contributions of the hub to the publication.
• The PD(s)/PI(s) will attend two yearly meetings: (a) an annual meeting of the cryoET network, and (b) an annual meeting of all the projects supported by the Common Fund CryoEM and CryoET initiatives.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
• NIH staff (a Project Coordinator and a Program Official) have substantial programmatic involvement in oversight of project management.
• The NIH Project Coordinator is the NIH point-of-contact for the project, except for special circumstances designated by NIH. The Project Coordinator will attend all official business meetings of the project's leadership and must be kept informed of all substantive deliberations and developments affecting the project. The Project Coordinator will provide advice and guidance to ensure that the project adheres to the objectives of the FOA, the Terms and Conditions of the award, and other agreements between the awardees and NIH. The Project Coordinator will keep the PD(s)/PI(s) informed of any issues and concerns involving the project and provide advice on how to address them. The Project Coordinator will not make decisions about the funding of this project, and will not be involved in any special reviews of the project that make recommendations about funding. The Project Coordinator will not co-author publications with project investigators.
• Additionally, an NIH Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Program Official will monitor the delivery of services to the community on a continuing basis and will formally evaluate the project on a yearly basis. The Program Official must approve in advance (i) changes in the roster and effort of the PD(s)/PI(s) and key personnel, (ii) changes and exceptions to the plans and commitments in the application, (iii) changes in the scientific scope of the project, (iv) changes to the frequency of business meetings, and (v) services for and partnerships with for-profit users. The Program Official will not co-author publications with project investigators.
• Annual Review. The yearly evaluation by the Program Official will be based on the non-competing application and progress report, service records, and assessments by the Project Coordinator. The Program Official will review the management, performance, and utilization of the hub. If concerns are identified by the Program Official, the Project Coordinator will work with the PD(s)/PI(s) to develop plans to address them in the next year of support.
• Special Reviews. NIH does not anticipate conducting special or mid-course reviews of scientific progress beyond the normal yearly non-competing progress review. However, if concerns are identified about the performance of the hub or the management of the project, the Program Official may conduct special reviews of the project as he/she deems necessary. NIH may engage outside experts to assist in these reviews. If concerns about the project arise and are not resolved, NIH may reduce or restrict the budget or reduce the term of support to phase out the project. In the event of long-term incapacitation of resource facilities, NIH may reduce the budget and/or term of support to phase out the project.
Areas of Joint Responsibility Include:
• Before the initial award is made, NIH and the awardees may negotiate clarifications, changes, or additions to the plans and commitments in the application. Future changes to these plans may be made by the NIH and the PD(s)/PI(s). Changes will be documented by an exchange of correspondence. NIH and the PD(s)/PI(s) will agree on the information to be included in the records management system and on performance elements prior to award and document them by an exchange of correspondence. They may be adjusted later by mutual agreement.
• The PD(s)/PI(s) and the NIH Project Coordinator will work together to monitor the technical performance of the hub and the delivery of services to users and to the other centers in the network on a continuing basis. NIH and the PD(s)/PI(s) will review and agree upon the balance between the delivery of user services and internal development activities on a continuing basis. NIH and the PD(s)/PI(s) will review records of the hub's activities and the progress of cross-training (described in Section 1. FOA Description) at the regular business meetings.
• Network Coordinating Group. The hub and the other centers funded through this initiative will participate with NIH staff in a Network Coordinating Group to share information and arrange for mutual assistance between centers. This group will design and run the user application and review process, and will allocate all network services for approved projects, including data collection services at the network nub. The Network Coordinating Group will organize an annual meeting of the PD(s)/PI(s) and key staff of all the cryoET centers in the network. This hub will provide administrative and logistical support for the network's coordination activities.
• Centers Coordinating Group. The PD(s)/PI(s) and the Project Coordinator of the hub will participate in the Centers Coordinating Group with the National Centers for CryoEM that were funded by the Common Fund RFA-RM-17-002. The hub will represent the cryoET network in that group. This group will coordinate sharing of information and mutual assistance between centers. This group may meet by telephone.
Term of Support, Administrative Review:
The initial budget period will be four years. An additional two years may be granted contingent upon the outcome of an administrative review of progress by NIH. The administrative review will be based on (i) the Research Performance Progress Report (RPPR) for year 04 of the project, (ii) a summary of progress during the first three years and ten months of support, (iii) a summary of plans for phase 2 (years 5-6) of the project, and (iv) information in the RMS. Items ii and iii should be included in the annual RPPR for year 04. NIH may request additional information from the grantees for this review.
The administrative review will assess whether the center is progressing appropriately in establishing its infrastructure, recruiting and training its staff, establishing workflows, and providing user services. In the administrative review, NIH will take into account the setup period and the challenges of the research. As is appropriate, the administrative review will consider the performance elements agreed upon by NIH and the PD(s)/PI(s) prior to award and documented by an exchange of correspondence.
Special requirements:
As specified in Section I. Funding Opportunity Description (Scientific Scope), hub staff should not be co-authors on users' publications for standard services and cross-training that they deliver as hub employees. The PD(s)/PI(s) must disclose this restriction to potential employees. Persons who (i) hold a Ph.D. or equivalent degrees and/or (ii) need authorship on publications to document their professional accomplishments must have individualized professional development plans, and these plans must be approved by NIH. It is recommended that these individuals not have greater than 75% effort at the hub, and that the institution make provisions for these individuals to engage in research during the remaining 25% of their effort, including commitments for environment and resources.
For any graduate students or postdoctoral fellows working in a staff capacity in the hub, an individualized professional development plan is required and must be approved by NIH. These plans should include a signed letter from the graduate program director, dean for graduate or postdoctoral affairs, or similar institutional official with responsibility for training oversight, stating that he/she is aware of the trainee's work in the hub and that it benefits the student/postdoc's training and career goals. Students or postdocs working as hub staff should generally not spend more than 25% of their time in such a capacity.
Dispute Resolution:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened: a designee chosen by the PD(s)/PI(s), one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.A final 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.
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.
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Paula Flicker, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Email: [email protected]
Raymond Jacobson, Ph.D.
Center for Scientific Review (CSR)
Email: [email protected]
Dina Wilson
National Institute of General Medical Sciences (NIGMS)
Email: [email protected]
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.