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 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.

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Background

This funding opportunity announcement (FOA) is for support of National Centers for Cryoelectron Microscopy (CryoEM) that will strengthen research capacity in cryoEM by providing access to and training in advanced cryoEM technologies. Centers will provide economies of scale by concentrating expertise and state-of-the-art equipment and lower the barrier to entry to serve a broad and diverse range of users and institutions.

CryoEM has unique capabilities for the study of biological systems that are inaccessible to other structural methods. Technical advances in single particle cryoEM in the past decade have enabled the generation of reliable atomic models of complete and fully functional macromolecular complexes. Furthermore, cryoEM can resolve distinct species in mixtures, allowing analysis of complexes in different functional states.

The prohibitive cost of microscopes, the required computational capacity for data analyses, and large operating expenses pose a barrier to the wider utilization of cryoEM. This program will support centers to provide access to this technology. Expertise availability also limits wide utilization of cryoEM. Specimen preparation is a trial-and-error process that requires intuition and skill. Similarly, although software for analysis of cryoEM data has improved greatly in speed and ease of use, computation must be customized for the specimen, parameter optimization is performed manually, and built-in safeguards against errors are incomplete. These centers will increase the number of investigators who can independently practice cryoEM by training researchers in all steps of structure determination including sample preparation and evaluation, collection of high-resolution data, theory, and rigorous and reproducible data analysis.

Program Objectives

This program will support up to three established service centers to provide nationwide access to cryoEM technology and increase the number of researchers with cryoEM expertise. The instrumentation performance and quality of data produced will equal or set current state-of-the-art standards.

The major objectives of the centers include:

• Provide Specimen and Data Services for collection of high-resolution cryoEM data for user research projects
• Lower the barrier of entry to researchers with no cryoEM experience by providing Screening Services that enable specimen preparation and screening to produce data-collection-ready samples
• Increase the number of well-trained cryoEM practitioners by providing User Training in the theory and practice of cryoEM

A priority of this FOA is to increase national expertise in cryoEM by enabling center users to work independently rather than having center staff solve structures for them.

Centers must be established and ready to operate upon award. Each center must have, at a single institutional site, at least four state-of-the-art 300kV cryoEM microscopes equipped with direct electron detectors for high resolution data collection, and at least one cryoEM microscope for specimen screening. They should already have in place all other necessary instrumentation and physical infrastructure, as well as computational resources, web-based informational and user access tools, and a proposal application and review system.

Centers should offer equal-opportunity access to services through a nationwide, open application process with the goal of serving a broad and diverse range of users and institutions. Access should be prioritized through a formal scientific review process by a User Review Committee and programmatic and administrative review by center staff.

NIGMS recognizes that diverse teams working together and capitalizing on innovative ideas and distinct perspectives outperform homogeneous teams. There are many benefits that flow from a diverse scientific workforce, including: fostering scientific innovation, enhancing global competitiveness, contributing to robust learning environments, improving the quality of the research, advancing the likelihood that underserved populations participate in and benefit from research, and enhancing public trust. To support the best science, NIGMS encourages inclusivity in research. Examples of structures that promote diverse perspectives include but are not limited to:

• Transdisciplinary research projects and collaborations.
• Engagement from different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Individual applications and partnerships that enhance geographic and regional heterogeneity.
• Investigators and teams composed of researchers at different career stages.
• Participation of individuals from diverse backgrounds, including groups traditionally underrepresented in the biomedical, behavioral, and clinical research workforce (see NOT-OD-20-031), such as underrepresented racial and ethnic groups, those with disabilities, those from disadvantaged backgrounds, and women.
• Project-based opportunities to enhance the research environment to benefit early- and mid-career investigators.

This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see Section IV.2 SF424(R&R) Other Project Information. Other Attachments). For further information on the PEDP, please see https://braininitiative.nih.gov/about/pedp-key-elements-and-examples.

Specimen and Data Services. Each center should offer on-site, remote-access, and mail-in data collection services. Users with access to sample preparation and screening equipment will perform as much of the preparatory work as they can at their own sites, and then bring or send samples to the center. Center personnel will handle standard data collection tasks at the center site and provide feedback to the user as appropriate. Reasonable accommodation should be made for special data collection needs, which may require users to participate remotely or on-site to provide direction and assistance.

Screening Services. The centers should provide screening services to users who have no access to sample preparation and screening equipment and for specimens that must be prepared on site. They should provide necessary facilities for preparing, optimizing, and screening frozen specimen grids. Center staff are expected to advise and support users in use of these facilities.

Design of center operations and communication should maximize returns from the users' investment of time and materials. Center staff should work with users from the beginning of the application process to ensure that specimens are image-ready and data collection protocols are appropriate. Center personnel should provide technical support as needed to maximize throughput and efficiency and optimize the quality and quantity of high-resolution data.

Operations should seek to maximize productive hours of high-end microscope operation. Centers should implement workflow and state-of-the-art technical measures to recognize and troubleshoot data collection or quality problems in real time. At their discretion, centers may choose to qualify some users to operate equipment without supervision and provide a certification credential to the user that confirms proficiency. Centers should be equipped and operated to minimize the impact of instrument outages and other service interruptions.

Centers should perform standard initial processing and correction of raw image data if requested by users. Beyond the computation needed for first pass processing of collected data, centers should provide sufficient high-end computing capacity to allow users to complete straightforward analyses of data sets that do not require unusual amounts of computer time.

The objective of the centers' specimen and data services is to provide users with access to advanced instrumentation and associated technical support, rather than research collaboration. Except under unusual circumstances where conceptually new methods are developed for a user, center personnel providing standard technical advice and support should not be co-authors on publications. The expert assistance of center staff may be credited by name in the acknowledgments section of publications.

User Training. Centers should provide introductory guided research experiences in both the experimental practice of cryoEM and in cryoEM theory and analysis. Centers should help qualified researchers develop the skills needed for independent research in cryoEM by guiding them through the steps of determining their structures, including the preparation and evaluation of samples for cryoEM, collection of high-resolution data, and data analysis. Users may schedule periodic visits or embed personnel at the centers for more extended stays.

Centers should train as many researchers as is practical while maintaining high standards and should participate in users' research only in accordance with a training plan. In cases where center personnel make significant intellectual contributions to a user's project, they may be included as coauthors on publications. However, since a goal of training is to assist new users in establishing credentials through lead authorship on publications, center PD(s)/PI(s) should avoid or minimize co-authorships. After completing their training, new users should not depend on in-depth involvement of the center in their research. Users who need extensive long-term assistance with projects should be referred to an external collaborator.

Expectations of Center

Information Sharing Activities. Centers must ensure equitable access to these national facilities and are expected to inform the scientific community of their capabilities and services, promote broader application of cryoEM, and actively recruit users.

Research. Centers may engage in research that directly advances their service objectives. For example, centers may develop technology to improve their data collection capabilities during the approved project period. Technology development that does not directly advance the center's service objectives is beyond the scope of this FOA and may be supported by funding through other sources such as the NIGMS Technology Development Programs R21 (PAR-22-126) and R01 (PAR-22-127).

User Charges. There will be no facility charges for non-profit use.

User Accommodation. Convenient lodging, meals, and transportation must be available to users at reasonable cost.

Data and Data Sharing. Center users, not the center itself, are responsible for long-term storage of any data generated from user samples. As a condition of use of center services, users must agree to follow all applicable NIH policies for the sharing of their data and research resources, as appropriate.

Record Keeping and Progress Reviews. Centers should keep records to track activities, applications, users, specimens, microscope usage, outcomes, and user feedback. They should be kept current and accessible for review by the PD(s)/PI(s) and summarized in the annual progress reports. The records system should be used to track progress in the following items:

• Applications and Review. Types and numbers of applications received, review evaluations, and outcomes.
• User Base. Users served (persons visiting, institutional affiliation, career level, instrument time allocation). Type of project (data collection, screening, training). Breakout of visits (in person, remote, mail-in). Geographic distribution.
• Service summaries. Types of services provided. Screening (number of projects, screening, outcomes). Data collection (number of projects, number/size of data sets) and outcomes (quantity/resolution, usability, status). Training (number of projects, visit type, topics covered, certifications received).
• Microscope use. Log of hours for each microscope for: Center usage days, Idle days, Time unavailable for cause (repair/downtime, holidays, etc.).
• Workshop training. Dates, location, and topics of workshops. Number of attendees, in-person, virtual, hands-on access. Evaluation outcomes.
• Impact on User Research. Publications list. Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB) deposition numbers for all publications supported. Funding sources and grant numbers for all center-supported projects.
• Report on activities related to the Plan to Enhance Diverse Perspectives (PEDP). For example, list efforts to provide training to individuals from underrepresented groups and outcomes from those efforts.

Application Process. There should be a single public application track for all users, including local and institutional users. Except for the center's own internal development, quality control, maintenance, and evaluation projects, other institutional or local use must be reviewed and prioritized through the same public channels as all other users.

The review process for applications for instrument usage and training should be consistent with the objective of equal opportunity nationwide access to state-of-the-art cryoEM equipment, technical support, and training. Describe the application and review processes. The PD(s)/PI(s) must engage a User Review Committee to provide scientific and technical reviews of user applications for services at their center.

Staffing. Since professional effort on center appointments will be mainly service-related activities, centers are encouraged to develop strategies for the recruitment and development of highly qualified staff. Center personnel with part-time appointments may participate in research outside of the center, provided their effort on this research is supported by other funding sources. Center staff should apply as external users through the center's public application process for use of center facilities for their outside research.

Website. Each center should have a website that provides up-to-date and complete information about facilities and services, policies, and the application process.

Advisory Committees. Although the PD(s)/PI(s) may utilize an Advisory Committee for the center, this is optional and such a committee would not involve NIH personnel.

Partnerships. Centers may form partnerships that advance their mission. Examples include, but are not limited to, partnerships with instrumentation manufacturers/vendors and collaboration with academic technology developers. The centers funded through this FOA may coordinate on:

• A shared website for centers in the program
• Providing backup when service interruptions occur
• Coordination on user application reviews
• Sharing best practices and newly developed technologies
• Developing and cross-honoring training certifications in standard practices

Scientific Scope. This FOA specifies restrictions on purpose and scientific scope, and on the content that can be included in the application. Applications that are not responsive to the objectives of the FOA or request support that is outside its scope will not be reviewed. Because of the restricted scope, special application instructions, and additional review criteria of this FOA, potential applicants are strongly advised to discuss their plans with the Scientific/Research contact listed in Section VII below.

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 FOA.

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

Only institutions operating a cryoEM center with all microscopes at a single site may apply. The currently operating center must include a minimum of four 300keV high-resolution cryoelectron microscopes for data collection purposes, each equipped with direct electron detectors, and a minimum of one lower resolution microscope appropriate for initial specimen assessment prior to data collection. 100% of the time on the microscopes must be committed to center use.

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.

Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.

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.

• 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 SF424 (R&R) Application Guide.

At least one PD/PI should be an expert in single particle cryoEM and at least one PD/PI should have experience managing a scientific resource. These roles can be fulfilled by the same person.

2. Cost Sharing

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

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 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

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 FOA. 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 SF424 (R&R) Application Guide except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

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:

Paula Flicker, Ph.D.
Email: Paula.Flicker@nih.gov

Page Limitations

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

SF424(R&R) Cover

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Project/Performance Site Locations

All instructions in the SF424 (R&R) Application Guide must be followed.

SF424(R&R) Other Project Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Facilities & Other Resources:

• Describe the microscope infrastructure to be provided, for purposes of both high-resolution data collection and sample screening.
• Explicitly indicate whether all the vendors' environmental specifications for microscopes, other instrumentation, and computers are being met. These include, but are not limited to, temperature, humidity, electric and magnetic fields, vibration, and electrical power.
• Describe microscope user access facilities, both for in-person and remote access.
• Describe the laboratory facilities that will be available to visiting users for biochemistry, cryoEM specimen grid preparation, and computation. Indicate the distances between the facilities comprising the center.
• 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 technology development.

Other Attachments: The following attachment must be included in the application:

Plan for Enhancing Diverse Perspectives (PEDP) (1-page maximum): All applications must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP should include a timeline and milestones for relevant components that will be considered as part of the review.

Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers, and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants, including those from under-represented backgrounds.

For further information on the PEDP, please see https://braininitiative.nih.gov/about/pedp-key-elements-and-examples.

This attachment should be titled Plan for Enhancing Diverse Perspectives . Applications that do not include this attachment will be withdrawn without review.

SF424(R&R) Senior/Key Person Profile

All instructions in the SF424 (R&R) Application Guide must be followed.

PD(s)/PI(s): Biosketches of the PD(s)/PI(s) should include their qualifications and experience in structure determination by single particle cryoEM. At least one PD/PI should be an expert in single particle cryoEM and one PD/PI (can be the same person) should have experience in scientific resource management.

Individuals who have PD/PI-level responsibilities and authority, or who bring the necessary 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.

The key personnel should include only individuals who have a direct and specific role in the center that should be described in the application. Names of existing committee members or other advisors can be provided. Names of potential, previously unaffiliated 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.

R&R Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

Funding may be requested for the supported activities described in Section I or other well-justified activities.

Budget Justification: In the budget justification, provide detailed information about support received or anticipated from other entities. This could include additional funding from other government agencies or institutional support, for example. Department of Energy Laboratory Directed Research and Development (LDRD) costs are not allowed.

Cost of living escalation should not be included in any cost categories. Any add-on costs in a budget year must be well justified.

Scientific and Technical Staff: For each staff position, describe the technical responsibilities. At least one PD/PI, preferably a PD/PI who is an expert in cryoEM, must devote a minimum of three person-months effort to the center.

Equipment: The budget justification section should include an evaluation of alternative instruments or manufacturers and should explain the use of all major equipment items. Price quotes should be included for equipment costing more than $25,000. Service contracts and extended warranties may be included as part of the equipment requests.

Service Contracts: Service contracts are allowed but the cost of those for existing equipment should be included in the $6,500,000 total costs per year cap.

Travel: Travel and other costs for center 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. Where feasible, NIGMS encourages the use of virtual meetings to reduce unnecessary travel time and costs.

Partnering Activities: Funds for support of a common website and activities to share information among funded centers are allowed.

PEDP Implementation Costs: Budget request may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement).

R&R Subaward Budget

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Cover Page Supplement

All instructions in the SF424 (R&R) Application Guide must be followed.

PHS 398 Research Plan

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Specific Aims: The Specific Aims should address the objectives described in Section I.

Research Strategy:

Infrastructure and Technical Operations: Describe how the center will be equipped. Describe how the instruments will be maintained and operated to achieve state-of-the-art performance. Describe how the intellectual resources (provided in Facilities & Other Resources) will assist in troubleshooting problems.

Capacity: Describe the capabilities and capacity of the center in terms of annual throughput for specimen preparation and screening, data collection, and computation. Describe the categories and extent of computational support for users, including for those who do not have access to adequate computing. Justify the adequacy of computational resources for the anticipated data production. Discuss the handling (volume, storage, security, disposal schedules) of raw data.

Data Collection Services and Screening Services: Describe the types of user access services that will be offered for users with data-collection-ready specimens and for users who do not have access to screening microscopes and sample preparation equipment.

Workflow: Estimate capacity to deliver user access and services in terms of annual throughput. Describe how the delivery of services will be managed and how the FOA's objectives for quality of user services will be met, including communication with users and scheduling.

Training: Describe the principles, strategies, and management of user training. Provide estimates of the training capacity in terms of annual throughput. Explain the management of space, facilities, and assistance for visitors. Explain the scheduling strategy and the balance between specimen and data services and training.

Training Certification: Describe methods, strategies and services that may be offered to standardize training in common practices in sample preparation, microscope operations, and data management and processing.

Staffing: Together, the Biosketches, 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.

Record Keeping: Describe how information regarding center operations and the delivery of services will be recorded and made accessible for review by the PD(s)/PI(s). Describe how follow-up information about outcomes will be obtained and made accessible. Describe how user feedback will be obtained and utilized to iteratively improve center performance.

User Application Process: Describe the principles and strategies for ensuring open and fair access to scientifically and geographically diverse users by the User Review Committee. 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.

Information Sharing: Describe the plans for informing the community about center services, promoting the wider application of cryoEM, and recruiting users. Describe the website; do not include URLs (e.g., if there exists a currently operating center).

Backup Plans: Describe plans for contingencies in which the facility is unable to perform its functions for an extended period (months or longer). The plan should include provisions for support (for example, alternative employment) of center personnel if they are unable to perform their resource support functions for an extended period.

Advisory Committee: If the center already includes an advisory committee, list the current members, and briefly describe their qualifications. If an advisory committee is proposed, 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 PDs/PIs, 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 webpage.

Letters of Support: Letters of support should be limited to persons who are named in the application and have a role in the project that is described in the application, for example, expert consultants or statements of commitment from institutional officials. Statements of commitment from institutional officials must be provided and 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 project role described in the application.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide.

Describe the major categories of resources likely to be produced and the plans for sharing them, as appropriate. Where applicable, the plan should specifically address computer algorithms and software (including source code).

Other Plan(s): Note: Effective for due dates on or after January 25, 2023, the Data Management and Sharing Plan will be attached in the Other Plan(s) attachment in FORMS-H application forms packages.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

• A data management and sharing plan is not applicable to this FOA.

Appendix: Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) 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 SF424 (R&R) 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 SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

PHS Assignment Request Form

All instructions in the SF424 (R&R) Application Guide must be followed.

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

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

4. Submission Dates and Times

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.

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.

7. Other Submission Requirements and Information

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 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 FOA 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 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 NIGMS. Applications that are incomplete or non-compliant will not be reviewed.

Applications must include a PEDP submitted as an Other Attachment on the SF424(R&R) Other Project Information form and statements of commitment from institutional officials as Letters of Support on the PHS 398 Research Plan form. Applications that fail to include this information will be considered incomplete and will be withdrawn without review.

Post Submission Materials

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

Section V. Application Review Information

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 equipment, technical support, and training as described in Part II. Section I "Funding Opportunity Description". For all the criteria, emphasis should be on the quality of services and technical outcomes for users, and not on specific users or research that will be accommodated.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the center 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 center 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 center that by its nature is not innovative may be essential to advance a field.

As applicable for the center 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 center 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 Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications will receive a written critique.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:

• 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.
• Geographic distribution.

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 VI. Award Administration Information

1. Award Notices

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient's business official.

Recipients must comply with any funding restrictions described in Section IV.6. 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.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their Institutional Review Board (IRB) or Independent Ethics Committee (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

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federal wide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, 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.

Should the applicant organization successfully compete for an award, recipients of federal financial assistance (FFA) from HHS will be required to complete an HHS Assurance of Compliance form (HHS 690) in which the recipient agrees, as a term and condition of receiving the grant, to administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, age, sex and disability, and agreeing to comply with federal conscience laws, where applicable. This includes ensuring that entities take meaningful steps to provide meaningful access to persons with limited English proficiency; and ensuring effective communication with persons with disabilities. Where applicable, Title XI and Section 1557 prohibit discrimination on the basis of sexual orientation, and gender identity. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and https://www.hhs.gov/civil-rights/for-individuals/nondiscrimination/index.html

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. 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.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. For guidance on meeting the legal obligation to take reasonable steps to ensure meaningful access to programs or activities by limited English proficient individuals see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.htmlandhttps://www.lep.gov.

• For information on an institution’s specific legal obligations for serving qualified individuals with disabilities, including providing program access, reasonable modifications, and to provide effective communication, see https://www.hhs.gov/civil-rights/for-individuals/disability/index.html.

• HHS funded health and education programs must be administered in an environment free of sexual harassment, see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.

• For guidance on administering programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/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.

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 and 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.

Not Applicable

3. Data Management and Sharing

Note: The NIH Policy for Data Management and Sharing is effective for due dates on or after January 25, 2023.

Consistent with the 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.

Tracking the demand for and utilization of the resource is important for ongoing improvements in the short-term and for gauging the impact of usage on science in the long-term. A reporting plan tailored to the resource to best evaluate the productivity, availability, efficiency, and impact of the resource is required. Report data on an annual basis to track the demand for and utilization of the resource, as outlined in the Record Keeping section of the Research Strategy. Sample data should include the following:

• Applications and Review: Types and numbers of applications received, review evaluations, and outcomes.
• User Base: Users served (persons visiting, institutional affiliation, career level, instrument time allocation). Type of project (data collection, screening, training). Breakout of visits (in person, remote, mail-in). Geographic distribution.
• Service Summaries: Types of services provided. Screening (number of projects, screening, outcomes). Data collection (number of projects, number/size of data sets) and outcomes (quantity/resolution, usability, status). Training (number of projects, visit type, topics covered, certifications received).
• Microscope Use: Log of hours for each microscope for: Center usage days, Idle days, Time unavailable for cause (repair/downtime, holidays, etc.).
• Workshop Training: Dates, locations, and topics of workshops. Number of attendees, in-person, virtual, hands-on access. Evaluation outcomes.
• Impact on User Research: Publications list. Electron Microscopy Data Bank (EMDB) and Protein Data Bank (PDB) deposition numbers for all publications supported. Funding sources and grant numbers for all center-supported projects.
• Report on activities related to the Plan to Enhance Diverse Perspectives (PEDP): For example, list efforts to provide training to individuals from diverse backgrounds, including those from underrepresented groups, and outcomes from those efforts.

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. NIH FOAs 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 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. 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 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

In carrying out stewardship of grant programs, NIGMS will periodically evaluate the National CryoEM Centers program, employing the measures identified below. In assessing the effectiveness of the program in serving the needs of the research community and evaluating research capacity building investments, NIGMS may use information from progress reports and public databases, PD/PIs, and from participants themselves. Where necessary, PD/PIs and participants may be contacted after the completion of the grant period for updates on participants subsequent outcomes.

In evaluating the R24 National CryoEM Centers Program, NIGMS expects to use the following measures:

• Characteristics of the applicant and awardee pool for the program.
• Measures of resource utilization across the program, such as:
  • Information about the size and characteristics of the userbase.
  • Instrument time requested and fulfilled.
  • Amount (e.g., images, data sets) of high-resolution cryoEM data collected.
  • Publications, PDB, and EMDB depositions citing use of the resource.
• Indicators of research community outreach and engagement, such as:
  • Availability of user training materials.
  • Provision of workshops, seminars or other means of training.
  • Evidence of activities to publicize services provided.
  • Enhanced recruitment of researchers from diverse backgrounds, including those from underrepresented groups.

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: GrantsInfo@nih.gov (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: support@grants.gov

Paula Flicker, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Email: Paula.Flicker@nih.gov

James Mack, Ph.D.
NIH Center for Scientific Review (CSR)
Email:mackj2@mail.nih.gov

Jen Billington
National Institute of General Medical Sciences (NIGMS)
Email: Jennifer.Billington@nih.gov

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 45 CFR Part 75 and 2 CFR Part 200.