National Institutes of Health (NIH)
National Centers for Cryoelectron Microscopy (U24)
U24 Resource-Related Research Projects – Cooperative Agreements
This NIH Common Fund initiative will establish national service centers to increase research capacity for molecular structure determination by high resolution cryoelectron microscopy (cryoEM). The centers will address Common Fund infrastructure and workforce goals for cryoEM by providing access to state-of-the-art equipment, technical support, and cross-training for the production and analysis of high-resolution data. The centers will offer equal-opportunity nationwide access to services through an open application process.
January 5, 2017
May 30, 2017
May 30, 2017
June 30, 2017, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date.
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.
July 1, 2017
It is critical that applicants follow 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 the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
Purpose. 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. Cryoelectron microscopy (cryoEM) has been selected for Common Fund support because it opens up previously inaccessible levels of biological organization to high resolution structure analysis, and will vastly extend the range of functions and interactions that can be targeted for basic research and structure-based development of therapeutics. To capitalize on these opportunities, this initiative has two goals for increasing research capacity in cryoEM: first, provide nationwide access to advanced cryoEM technical capabilities, and second, assist new users in the development of cryoEM skills needed for independent research.
Background. CryoEM has unique capabilities for the study of biological systems that are not accessible to other structural methods. Recent technical advances in single-particle cryoEM have made it capable of generating reliable atomic models of complete and fully functional macromolecular complexes. This method does not require crystallization and needs only small amounts of sample. It can resolve different structures in mixtures that vary in composition and conformation, allowing for the analysis of complexes in different functional states. An emerging related cryoEM method, cryoelectron tomography (cryoET), can image macromolecular assemblies in intact unstained frozen cells in 3-D. Together, these methods enable high-resolution analysis of previously inaccessible levels of biological organization, ranging from below 100kD to whole cells.
The cost of microscopes and their operating expenses are prohibitive for most research institutions in the United States, and have been a barrier to the wider utilization of cryoEM. This initiative will establish centers to provide access to this new technology. Because most analyses pose unique technical problems that require experience and insight to solve, research expertise is also limiting for the wider application of cryoEM. Specimen preparation is still a trial and error process that requires intuition and skill. Computation must be customized for the specimen; optimization of parameters is still performed manually, and built-in safeguards against errors are incomplete. At its current state of art, expertise in mathematics, physics, and macromolecular structure are needed to master the theory of cryoEM in enough depth to ensure reliable results. These centers will increase the number of investigators who can independently practice cryoEM by cross-training laboratories from structural biology and other fields in all steps of analysis: the preparation and evaluation of their samples for cryoEM, collection of high resolution data, theory, and computational analysis.
Research Objectives and Scope. This program will establish up to three service centers to provide nationwide access to cryoEM technology and contribute to the development of cryoEM expertise. The primary objective of the centers is the collection of high resolution data for user laboratories. Users will prepare and pre-screen samples; center personnel will give users informative feedback about their samples and collect high quality data sets. The performance of instrumentation and quality of data produced will equal or set current state-of-the-art standards. The secondary objective of the centers is to increase the number of well-qualified new practitioners of cryoEM by cross-training laboratories established in other fields. One priority of this FOA is to enable researchers in other fields of structural biology to adopt single-particle cryoEM methods. The goal is to achieve a catalytic effect by increasing research capacity; this will be accomplished by enabling investigators to work independently, rather than by solving their structures for them.
Centers 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 scientific review by a User Review Committee and programmatic and administrative review by center staff.
Specimen andData Services. Once fully equipped, each center should have at least two state-of-the-art 300kV cryoelectron microscopes equipped with direct electron detectors for high resolution data collection, and two cryoelectron microscopes for specimen screening. The center should have cryoET capabilities, and offer on-site, remote-access, and mail-in data collection services. Users will perform as much of the preparatory work as they can at their own sites, and then bring samples or send prepared frozen grids to the center. When image-ready specimens can be shipped, center personnel will handle standard data collection tasks at the center site. Reasonable accommodation should be made for special data collection requirements, which may require users to participate remotely or on-site to provide direction and assistance.
For specimens that must be worked up on site, centers will provide wet lab facilities for biochemistry and cryoEM support facilities for preparing and screening frozen specimen grids and microscopes for screening. Center staff will advise and support users in the use of these supporting facilities.
Center operations and communication should be designed to optimize returns from the users' investment of time and materials. Center staff will 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 will provide technical support as needed to maximize throughput and efficiency, and optimize the quality and quantity of high resolution data. 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 center facilities and services. Operating procedures should be designed to minimize miscommunication, equipment outages, technical incompatibilities, and other time-wasting delays.
Operations should seek to maximize productive hours of high-end microscope operation. To productively utilize microscope time, center personnel and users should monitor the quality of data as it is collected and make adjustments as needed. Centers should implement workflow and state-of-the-art technical measures to recognize and troubleshoot data collection problems in real time. At their discretion, centers may choose to qualify some users to operate equipment without supervision. Center staff will assist them as needed with the adjustment and operation of equipment. Centers should interface effectively with vendors for service arrangements that minimize instrument downtime. Centers should be equipped and operated to minimize impact of instrument outages and other service interruptions.
Centers will perform standard initial processing and correction of raw image data if requested by users. Users may choose to process their raw data at their home institutions, or to perform motion correction and particle picking at the center. 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 generally not be co-authors on publications. The expert assistance of center staff may be credited by name in the acknowledgements section of publications.
Cross-training. Centers will provide introductory guided research experiences according to users' needs in both in the experimental practice of cryoEM and in cryoEM theory and analysis. Centers will help qualified laboratories (or partnerships of collaborating laboratories) develop the skills needed for independent research in cryoEM by guiding them as they perform the steps of solving their structures, including the preparation and evaluation of samples for cryoEM, collection of high resolution data, and data analysis. Laboratories may schedule periodic visits or embed personnel at the centers for more extended stays.
Cross-training in cryoEM theory and analysis should include image processing, reconstruction, refinement, and the generation and the derivation of atomic structures from density maps. Guidance in theory and computational analysis should inform new users about best practices, rigor, and quality control measures that ensure reliable analyses and outcomes. These topics should include selection and optimization of software parameters, metrics for the evaluation of the quality of data and results, customization of analyses for special circumstances, potential sources of error, bias, and artefacts, and best practices for error checking and troubleshooting. Laboratories cross-training in theory and analysis should have enough expertise in mathematics, physics, and structural biophysics to be able to independently perform scientifically rigorous and correct cryoEM structure analysis after their cross-training. Laboratories in related fields of structural biology and biophysics are candidates for cross-training, but others may also be appropriate. Two or more collaborating laboratories that collectively possess the needed expertise may also be appropriate.
Centers should cross-train as many new laboratories as is practical while maintaining high standards. The intent of research guidance is to help new users acquire cryoEM skills and prepare for independent research, rather than to engage them in long-term collaboration. Thus, centers need to strike the correct balance between providing an adequate introduction to cryoEM to new laboratories without being drawn into an extended collaborative role in their research. Centers should participate in users' research only in accordance with a cross-training plan. After completing their cross-training experience, new users should not depend on in-depth research involvement of the center in their research.
Centers should complete cross-training and transition new users to independent research in a timely manner. To assist the transition from center assistance to independence, centers may offer guidance about opportunities for research collaborations with cryoEM experts outside the center. Users who need extensive long-term collaborative assistance with difficult projects should be referred to an external collaborator. The PD(s)/PI(s) and the NIH Project Coordinator will regularly review the progression of laboratories through cross-training to independence from center assistance.
In cases where center personnel make significant intellectual contributions to a published study in the course of providing research guidance, they should be included as coauthors on publications. One goal of cross-training is to assist new users in establishing credentials through lead authorship on publications. The center PD(s)/PI(s) should avoid or minimize co-authorship on users' research publications.
Cryoelectron tomography (cryoET). Since one goal of this FOA is to expedite integration of single-particle cryoEM into research programs in closely related fields of structural biology, initial priority should be given to single particle analysis. However, in anticipation of increasing demand for cryoET, centers should equip themselves for cryoET data collection and may accept users and offer cross-training in this subspecialty. After the centers have had an opportunity to assess the demand for cryoET and the impact of recent technical advances on their ability to offer services, the PD(s)/PI(s) and the NIH Project Coordinator may choose to adjust this priority.
Information Sharing Activities. Centers will all draw from the same national pool of potential users, and are individually responsible for ensuring that the capacity of their facilities is productively utilized. Centers are encouraged to carry out activities to inform the scientific community about their capabilities and services, promote broader application of cryoEM, and actively recruit users.
Partnerships. Centers may form partnerships that advance their mission. Examples include but are not limited to collaboration with academic researchers and technology developers, and partnerships with manufacturers/vendors of instrumentation.
Research. Centers may engage in research that directly advances their service objectives. For example, centers may develop technology that is expected to improve their data collection capabilities during the approved project period. Longer-term technology development that will not directly advance the center objectives during the project period is outside the scope of this FOA. Although this is encouraged, it should be supported by other funding sources.
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 are responsible for long-term storage of their data. 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 will operate a records management system to track all center activities, applications, users, specimens, outcomes, and user feedback. It should be kept current and accessible for review at all times by the PD(s)/PI(s) and NIH; periodic reviews of these records will be conducted at the regular business meetings as described in Section VI.2, Cooperative Agreement Terms and Conditions of Award. The records system should include:
User Review Committee. The PD(s)/PI(s) must appoint a User Review Committee to provide scientific and technical reviews of user applications for services at their center. 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.
Priority of Access to Center Services. Informed by scientific and technical review by the User Review Committee, center staff should allocate and schedule time in accordance with objectives of this FOA. As demand for services develops to exceed capacity, centers should institute transparent review criteria and apply them consistently in prioritizing access to center services. Scientific review for all services should consider scientific rationale, the suitability and status of the specimen, technical feasibility, and the effort and resources needed to provide the service. Scientific review for cross-training should assess the potential for applicants to progress to independent cryoEM research, including the applicant laboratory's cross-training goals and plan, follow-up plans, time commitment, and the number of personnel who will be cross-trained. For cross-training in single-particle data analysis, review should assess the applicants' technical qualifications and potential to master the theory and best practices needed to conduct rigorous work. Administrative review by center staff should consider the breadth and diversity of supported users and institutions, the breadth and diversity of supported scientific topics, provision of sufficient access to complete the work or cross-training, and other resources available to users. As far as is possible, the scheduling process should optimize travel and lodging for users.
Application Process. Access to center facilities and services should be allocated nationwide solely in accordance with a formal application and review process. There should be a single public application track for all users, including local and institutional users. With the exception of the center's own internal development and evaluation projects, other institutional or local use must be reviewed and prioritized through the same public channels as all other users, including use of unassigned or idle capacity.
Staffing. The center PD(s)/PI(s) must include one or more individuals with expertise in high resolution cryoEM. That is, skills and knowledge of cryoEM are necessary to qualify for eligibility in Section III.1. However, it is not required that every PD/PI be a cryoEM expert. Providing services and research guidance at the current state of the art requires personnel who are experienced and knowledgeable in cryoEM. Since professional effort on center appointments will be mostly service-related activities, centers are encouraged to develop strategies for the recruitment and development of highly-qualified staff that go beyond the limited opportunities that are available within the centers' mission. Center personnel with part time appointments may participate in research outside the center, provided their effort on the outside research is supported by other funding sources. Center effort and facilities should be kept separate from this external research. Center staff should apply as outside users through the center's public application process for use of center facilities for their outside research.
Website. The center should have a website which 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. 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.
Centers Coordinating Group. The centers funded through this FOA and NIH staff will participate in a committee to share information and arrange for mutual assistance between centers. The Centers Coordinating Group will organize an annual one-day meeting of PDs/PIs and key staff of all the centers. The group will also monitor the consistency of the criteria used by the Centers' respective User Review Committees for scientific and technical review of user applications. This group will facilitate coordination on (i) referral of duplicate applications for services, (ii) referral of applicants between centers if another center can provide better accommodation or specialized center services, (iii) sharing workload to clear backlogged requests, (iv) providing backup when service interruptions occur, and (v) sharing best practices and newly-developed technologies.
Scientific Scope. This FOA specifies restrictions in purpose and scientific scope, and in 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.
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.
The NIH Common Fund intends to commit approximately $18,800,000 for FY 2018, contingent upon receiving scientifically meritorious proposals. Two or three are anticipated from this solicitation.
The maximum yearly budgets (total costs) are
$9,400,000 for year 1,
$12,800,000 for year 2,
$7,600,000 for year 3,
$4,200,000 for year 4,
$4,700,000 for year 5, and
$4,300,000 for year 6.
The maximum project period is six years.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
o Hispanic-serving Institutions
o Historically Black Colleges and Universities (HBCUs)
o Tribally Controlled Colleges and Universities (TCCUs)
o Alaska Native and Native Hawaiian Serving Institutions
o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are not allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Buttons to access the online ASSIST system or to download application forms 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.
It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Mary Ann Wu, Ph.D.
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.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities & Other Resources: 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 of 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.
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 technical development.
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, which may include documentation of (a) an active research program in high-resolution cryoEM, (b) leadership in solving challenging research problems in cryoEM, (c) technical innovation in carrying high resolution cryoEM structure analyses through to publication, (d) experience in acquiring, maintaining, and operating state-of-the art cryoEM instrumentation, including troubleshooting instrumental, environmental and other technical problems, (e) experience organizing collaborative research efforts and/or managing a resource, and (f) skills in recruitment, management, and negotiation. At least one PD/PI must be an expert in single particle cryoEM; the R&R Budget instructions specify the minimum effort required for this individual. Qualified individuals who do not hold academic appointments, for example, a facility director/manager, may serve as PDs/PIs.
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 already be identified and To-Be-Named is acceptable.
The key personnel should include only individuals who have a direct and specific role in the center 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.
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.
Scientific and technical staff. For each staff position, describe the technical responsibilities. The required PD/PI who is expert in single particle cryoEM must devote a minimum of three months' effort to the center.
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. The budget should include funds for travel to a one-day annual meeting of the PDs/PIs and key staff members from all the centers.
Service Contracts are allowed.
Cost of living escalation should not be included in any cost categories.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Specific Aims: The Specific Aims and Research Strategy should address the objectives described in Section I and should not include other research.
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. 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.
Capacity. Describe the capabilities and capacity of the center for specimen preparation and screening, data collection, and computation. Describe the categories and extent of computational support for users. Explain the extent of the computing support that will be made available to users who do not have access to large scale computing, including users from smaller institutions. Justify the adequacy of computational resources for the expected production of data. Discuss the handling (volume, storage, disposal schedules) of raw high-throughput data.
Services. Describe the kinds of user access services that will be offered. 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.
Workflow. Estimate capacity to deliver user access and services. Indicate how services will be allocated in response to demand. Explain how effort on specimen preparation, data collection, and data analysis will be coordinated to maximize efficiency.
Cross-training. Describe the principles, strategies, and management of cross-training. Describe the topics and estimate the staff time and facility usage to cross-train typical users. Provide estimates of the capacity for cross-training. Explain the management of space, facilities, and assistance for visitors. Explain the scheduling strategy and the balance between specimen and data services and cross-training.
Staffing. Together, the Budget Justification and Research Strategy should explain the qualifications and roles for each staff positon. Describe how well-qualified staff will be recruited, trained, and retained.
Record Keeping. Describe how information about center operations and the delivery of services will be recorded and made accessible for review by the PD(s)/PI(s) and NIH Project Coordinator. 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. 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.
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 consortium personnel if they are unable to perform their resource support functions 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. 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 webpages (http://www.grants.nih.gov/grants/multi_pi/ ). 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.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
The Resource Sharing Plan should explain how the center and users will follow all applicable NIH policies and guidance for sharing of resources and data generated by the center.
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
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 Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by the Division of Program Coordination, Planning and Strategic Initiatives, Office of Strategic Coordination, NIH (Common Fund). Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
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 cross-training as described in 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. Since strategies will need to be adapted with experience and changing circumstances, review emphasis should be on the qualifications of the investigators and the principles behind their strategies to deliver the specified services.
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 center address the needs of the research community that it will serve? Is the scope of activities proposed for the center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the center?
FOA additional questions: How well will the proposed center meet the objective of nationwide access to state-of-the-art equipment and technical support? How effective will the center be in assisting new users to develop cryoEM skills and transition to independent research?
Are the PD(s)/PI(s) and other personnel well suited to their roles in the center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing high resolution cryoEM research? Do the investigators demonstrate significant experience with coordinating basic research? If the center 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 center? Does the applicant have experience overseeing selection and management of subawards, if needed?
FOA additional questions: Do the PD(s)/PI(s) have experience and expertise in the determination of atomic structures by cryoEM? Do they have a record of solving challenging technical problems in cryoEM? 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 cryoEM specimen preparation, microscopy, and structure analysis? 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 center 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 collaborative research efforts and/or facility management? Do they have a history of performing services for the scientific community at large? Will they be well-suited to running a service facility whose scope is limited to data collection and guidance of outside users?
Does the application propose novel organizational concepts, management strategies, training strategies or instrumentation in coordinating the research the center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies, training strategies or instrumentation proposed?
FOA additional questions: Does the application include original strategies for assisting new users in the development of cryoEM skills? Does the application include original 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 the center? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the center program, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the center is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the center? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?
FOA additional questions: Is the approach appropriate to accomplish the objective of equal opportunity nationwide access to state-of-the-art equipment, technical support, and cross-training? Does the research strategy adequately address administrative and technical issues and challenges? Will the center be a leader in expanding the application of cryoEM?
Multiple PD/PI Leadership Plan (if applicable). If there are multiple PDs/PIs, 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?
Will the institutional environment in which the center will operate contribute to the probability of success in facilitating the research it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the center proposed? Will the center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?
FOA additional questions: For facilities and other resources that do not yet exist, will the plans for the microscope site and environmental controls meet vendor specifications? Are institutional commitments clear? For existing facilities, will they meet specifications? If the center relies on existing facilities, are they fully committed to the use of the center? 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 and specimen preparation facilities adequate for users who must prepare their specimens at the center? Are the workspaces comprising the facility adequate and in close proximity to each other?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following 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.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory General Medical Sciences Council. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. 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.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.
Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
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.
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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.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.
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.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
Areas of Joint Responsibility Include:
Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee 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 progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
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.
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
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
Contact Center Telephone: 800-518-4726
(Questions regarding application instructions and process, finding NIH grant
Email: GrantsInfo@nih.gov (preferred method of contact)
Mary Ann Wu, Ph.D.
National Institute of General Medical Sciences
Raymond Jacobson, Ph.D.
Center for Scientific Review (CSR)
National Institute of General Medical Sciences
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
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