Required Application Instructions

It is critical that applicants follow the 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.

Part 1. Overview Information
Part 2. Full Text of the Announcement
Section 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

The purpose of this Funding Opportunity Announcement (FOA) is to give laboratories specializing in cryoelectron microscopy (cryoEM) access to direct electron detection during the early years of deployment of this new technology.  It will support regional state-of-the-art data collection resources for cryoEM laboratories that do not have access to direct electron detection.  Because funds are limited, this FOA is a short-term initiative of restricted scope that addresses a specific immediate problem of research access for laboratories whose research programs are dependent upon cryoEM.  It is intended to support laboratories with an established independent specialization in cryoEM as reflected in publications and grants for established investigators, and publications for new investigators. 

This FOA will support multi-institutional consortia that comprise a host institution and regional participating institutions.  Consortia should include a minimum of 3-5 institutions, depending on the funds requested.  A consortium will support surplus capacity for cryoEM data collection (infrastructure and services) at the host institution and make it available as a resource for the participating regional institutions.  This FOA requires multiple Program Directors/Principal Investigators (PDs/PIs) and uses a cooperative agreement mechanism.  Each consortium will be directed by a team of multiple PD/PIs, one representing each institution.  See Section II for FOA-specific eligibility information and Section VI for FOA-specific cooperative agreement information.

Consortia will support access for cryoEM laboratories at participating regional institutions to resources and services at host sites.  Projects will (a) contribute to the fixed costs of maintaining the host facility and extend services in proportion to the capacity dedicated to the regional users and (b) support access to the facility by the regional laboratories.

The host institution should already have a modern high-performing cryoEM installation and proven capability for high-resolution data collection.  It should have sufficient capacity to accommodate the data collection needs not only of its own laboratories, but of the consortium users as well.  Given that improvements in the quality and throughput of data collection by cryoEM installations with direct detection may exceed an order of magnitude, we anticipate that a host institution will be able to accommodate not only laboratories at the host institution, but additional users as well.  The host institution need not already have an electron detector; this FOA can help fund acquisition of direct detection equipment.

The only research activity directly supported by these consortia is the collection of cryoEM data and the initial stages of processing the raw images by the participating regional laboratories.  The participating laboratories will complete their analyses of partially processed data at their home institutions.

The purpose of consortium funding is to enable data collection by the participating regional laboratories.  Funding to the host institution is to enable it to support a regional resource for users from non-host institutions.  Although this FOA does not support laboratories at the host institution, hosting a consortium may be advantageous for institutions that have surplus capacity for cryoEM data collection and need partners to share expenses for infrastructure.  Sharing of infrastructure expenses with a consortium may enable a host institution to support better infrastructure and services than it could afford without a partner.  

Since services at cryoEM installations are subject to interruptions by a variety of causes, NIGMS aims to achieve some redundancy of coverage with these consortia.  To ensure uninterrupted ability to collect data, eligible cryoEM laboratories may  participate in more than one consortium.  NIGMS staff will resolve any overlap issues between consortia after review. 

Awards will fund a specified fraction of the host institution's fixed expenses for operating the cryoEM installation, in return for its support of consortium investigators from non-host institutions.  Awards will fund travel, lodging, preparatory work, data collection, and data processing.  Awards can support service contracts, infrastructure expenses, personnel and operating expenses, consumables, repairs, software upgrades, data storage, and other expenses.  Applicants may request direct detection equipment where necessary (see Section II for budget limits).  Since the purpose of this FOA is regional access, it is important that projects include all provisions for travel, lodging and laboratory facilities needed to make it affordable, practical, and productive for regional consortium members to utilize the facility.

This FOA does not address all of the research needs that have been identified for cryoEM.  For example, these awards will not directly support (a) new users entering the cryoEM field, (b) research other than cryoEM data collection, and (c) service for non-specialists.  NIGMS will address the larger questions of broader access to cryoEM in its strategic planning process, which is now underway. 

Activities not supported by this FOA include (a) Adoption of cryoEM by new users.  Laboratories that do not already have an independent track record of specialization in cryoEM as an established research focus will not be supported by these consortia.  (b) Research.  It is expected that direct electron detection will open numerous research opportunities, not only for structure analysis, but also for technical research and development.  Although the infrastructure provided by this FOA will help enable such research, this FOA is intended only to support infrastructure and access, and not to directly fund research.  In this respect it differs from resources that support research applications and technology development in addition to service and infrastructure.  Consortia are dedicated solely to the purpose of data collection by the participating cryoEM laboratories and, and should not include other research activities.  (c)  Service.  These consortia differ from resources in which the host laboratory performs full service technical analysis for non-specialist collaborating laboratories.  They are dedicated solely to the purpose of data collection by the participating regional cryoEM laboratories and do not provide other services.

This FOA specifies restrictions in purpose, eligibility and scientific scope, including kinds of laboratories, PDs/PIs, and activities supported.  Applications that request support that is outside the scope of this FOA may be returned or receive lower priority in award consideration.  Important FOA-specific information is located in all sections of this FOA; see also section IV.6.

A FAQ (Frequently Asked Questions) for this FOA is posted at http://www.nigms.nih.gov/Research/Pages/CryoEM-Consortia-RFA-GM-16-001.aspx.  Because the restricted scope and special instruction for this FOA, potential applicants are strongly advised to discuss their plans with the Scientific/Research contact listed below.

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

• 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)

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)

• Eligible Agencies of the Federal Government

• U.S. Territory or Possession

Other

• Independent School Districts

• Public Housing Authorities/Indian Housing Authorities

• Native American Tribal Organizations (other than Federally recognized tribal governments)

• Faith-based or Community-based Organizations

• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign 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 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.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.

• System for Award Management (SAM) (formerly CCR) – 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. 
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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 DUNS number and 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 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 requires multiple Program Directors/Principal Investigators (PDs/PIs), which must be designated in accordance with the instructions in the SF424 application guide.  There should only be only one PD/PI per participating institution (grantee organization).  

Investigators (both multiple PD/PIs and participating laboratories) may participate in more than one application to this FOA.  CryoEM investigators who are not NIH or NIGMS grantees are welcome to apply to this FOA.  PD/PIs of existing cryoEM centers and research resources are welcome to apply. 

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:

• 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 NOT-OD-11-101).

In addition, the NIH will not accept a resubmission (A1) application that is submitted later than 37 months after submission of the new (A0) application that it follows.  The NIH will accept submission:

• To an RFA of an application that was submitted previously as an investigator-initiated application but not paid;

• Of an investigator-initiated application that was originally submitted to an RFA but not paid; or

• Of an application with a changed grant activity code.

An application can propose a consortium in which individual participating institutions have more than one eligible cryoEM laboratory.  An eligible cryoEM laboratory is an independent laboratory with an established independent specialization in and dependence on cryoEM as reflected in publications and grants for established investigators, and publications for new investigators.

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the “Apply for Grant Electronically” button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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:

• 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.

National Institute of General Medical Sciences (NIGMS)

Telephone: 301-594-0828

Email: flickerp@nigms.nih.gov

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 the capabilities of the host's microscope(s) and supporting facilities for high-resolution cryoEM data collection.  Describe laboratory facilities that will be available to visiting users.  Describe arrangements and costs of lodging and local transportation for visitors.

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

Heads of participating independent cryoEM laboratories who are not PD/PIs should be listed as key personnel.  Their biosketches should include their qualifications for membership in the consortium, referencing recent publications and grant support relevant to their participation.  The key personnel should include only the heads of participating independent cryoEM laboratories and expert consultants.  Senior support personnel in consortium laboratories (for example, facility managers) may be included in the budget justification but should not be listed as key personnel.

Previous experience with electron detectors and preliminary data from electron detectors are not required for the team, but teams should document their general qualifications and other experience relevant to adopting direct electron detection technology.  If teams lack direct experience with direct electron detection, they are advised to enlist expert consultants who can provide technical assistance.  

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

Applicants may request up to $500,000 for direct detection equipment where necessary.  Describe funds budgeted for participating regional laboratories to access the resource, for example travel, local transportation, and lodging.

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: 

Research Strategy.  The purpose of a consortium is to support resources and services for the participating independent regional cryoEM laboratories (i.e. not located at the host institution); these laboratories should be identified in a clearly marked section early in the Research Strategy. The research strategy should address the purposes of these consortia as described in Section I and should not include other research.  Specify the capabilities and services that will be made available to the participating regional laboratories.  Because the consortium will share facilities and services at the host site with other users (for example, laboratories at the host institution), specify the fraction of resources, time, and effort that will be dedicated to consortium services.

Significance.  The Significance section should address the purpose and priorities of this FOA. 

Approach.  Services.  Define the data collection capabilities that will be made available to the regional participating laboratories.  Describe the provisions and plans for processing of raw image data.  Describe how the microscope and supporting facilities for high-resolution cryoEM data collection will function.  Describe infrastructure support and services for users.  For each participating laboratory, describe the laboratory's scientific and administrative roles, interactions in the consortium, and how it will utilize the facilities. 

Resource Operations.  This FOA does not specify how grantees will organize or operate their resources.  Applicants must develop their own operating plans and describe them fully.  The research strategy should describe:  how communication will occur; how consortium personnel will be managed; resource allocation and scheduling; travel, lodging, and local transportation arrangements and costs; services and support; management of space and facilities for visitors; training of users; coordination of this award with other support and research obligations of the host site(s).  For each participating regional laboratory describe the number and duration of visits.  Estimate the expenses for regional users to visit the facility.  Describe how the needs and priorities of laboratories at the host institution will be balanced against those of consortium laboratories.

Describe provisions for dropping and adding participating laboratories.  The plan should explain how the performance of the resource will be monitored and evaluated and how scientific directions will be set.

Technical Operations.  Describe establishment and operation of direct detection technology;   performance standards and benchmarks; monitoring and maintaining instrument performance;   specimen preparation; data collection; computers and computation; software; data storage and transport. Identify the team members, who are not Senior/Key Personnel, who will provide needed expertise and be responsible for the various technical operations.

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 host institution 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 facilities.

Multiple PD/PI Leadership Plan

Describe how the PD/PIs will make and implement decisions about operations, personnel, and the project's budget.  Include mechanisms for making decisions and resolving disagreements.  Explain how the interests of consortium users and laboratories at the host will be represented and reconciled by the leadership team.  If there is more than one participating laboratory at an institution, explain how their interests will represented by one PD/PI on the leadership team. 

The sharing of management responsibilities by a team of PD/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 VI 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, 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 persons who do not have an assigned role in the project, for example, collaborators and users who are not consortium members.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

The Resource Sharing Plan should explain how the project will follow all applicable NIH policies and guidance for sharing of resources and data.

Resources.  Applicants are expected to 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).

Data.  Applicants are expected to identify data generated by the project that will be retained by the investigators but not be included in publications.  Discuss the disposition (storage, disposal schedules) of raw high-throughput data.  Identify categories of data that can be deposited in public databases and describe the plans for sharing them.  Identify categories of data for which public databases are not available, and describe the plans for sharing them.  If data will be analyzed and retained, and the conclusions but not the data published, describe the plans for sharing the unreduced data.  In all cases, estimate the volume of data that will be retained.

Appendix:  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 Planned Enrollment Reports as described in the SF424 (R&R) Application Guide. 

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide. 

Part I. Overview Information contains information about Key Dates. 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.

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.  If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by NIGMS, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Important FOA-specific information for applicants is included in several sections of this FOA in addition to Section I.  These include: 

Section II.  Award Information.  This section specifies the maximum award budget and project period. 

Section III. Eligibility Information.  Along with standard information, this subsection contains important FOA-specific information about PD/PI eligibility.

Section IV.  Application and Submission Information.  This section contains important FOA-specific application instructions, including Other Project Information (Facilities & Other Resources), Senior/Key Person Profile, Budget, Research Plan, Multiple PD/PI Leadership Plan, Letters of Support, and Resource Sharing Plan. 

Section V,  Application Review Information.  this section includes FOA-specific review criteria. 

Section VI.2,  Cooperative Agreement Terms and Conditions of Award, contains standard and FOA-specific information for applicants.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

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 sole purpose of this FOA is to provide support for regional access of cryoEM labs to state-of-the-art capabilities.  The review criteria should be applied in the context of the purpose and priorities of the FOA described in in Part 2, Section 1 ("Funding Opportunity Description"). 

This FOA is intended only to enable host institutions to house a shared regional resource that accommodates users from non-host institutions.  Other than proportionate support (cost sharing) for the portion of host infrastructure dedicated to regional access, this FOA is not intended to provide support to the host institution. 

This FOA is not intended to provide direct support for research activities, for example technology development or structure analyses.  Applicants were instructed to not include other research in their research plans.

For the Significance criterion, emphasis should be on the capabilities and regional accessibility of the infrastructure that will be supported.  Of particular importance are the expected regional benefits to geographically dispersed cryoEM laboratories.  For the approach criterion, emphasis should be on the effectiveness of the plans for delivering affordable regional access and advanced technical performance, rather than on the research that will be conducted at the facilities.

Although direct electron detection technology is new, experience to date indicates that the technology can be readily adopted by cryoEM investigators who are experienced in electron microscopy and computation.  Hence, review emphasis should be on the qualifications of the investigators to master the needed proficiencies, rather than prior direct experience, preliminary data, and technical detail.

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.

Significance

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Will the proposed resource significantly improve regional access of cryoEM laboratories to high performing direct electron detection capabilities?  Will the resource significantly improve the access of geographically distant laboratories to state-of-the-art data collection?    

Investigator(s)    

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? 

Do the participating laboratories have a track record of achievement in cryoEM?  Do the quality and breadth of the investigators' publication records indicate that the consortium team will be able to develop the proficiencies needed to implement and utilize direct electron detection technology?  Will the investigators be able to fill their assigned roles and be resourceful enough to solve the kinds of problems expected to arise in the course of the research?      

Innovation

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?  

Does the resource open new areas of opportunity to the consortium members?  Will the resource offer the capabilities needed to make novel findings and new perspectives in structural biology?  

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? 

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?  

Management plans.  Are the investigators 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? 

Research design.  Are the plans for establishing and operating the resource complete and sufficient?  Will access be affordable and practical for regional labs?  Is travel supported?  Are the participants' inclusion and roles justified?  Have practical benchmarks been set?  Are the plans for monitoring resource performance adequate?  If the applicants have not had extensive experience with direct electron detection, have they enlisted consultants and made provisions for getting any needed help? 

Environment

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?  

Will the microscope installation and computing facilities at the host site(s) be able to deliver reliable high-resolution and high-throughput cryoEM data collection?  Are accommodations for visiting consortium users (laboratory facilities and lodging) adequate?  

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.

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Children 

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.

Vertebrate Animals

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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 NIGMS, 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:

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

• Will receive a written critique.

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.

• Availability of funds.

• Relevance of the proposed project to program priorities.  Relevance to the special purposes and priorities of this FOA as described in Part 2, Section 1 ("Funding Opportunity Description") and the cost-effectiveness in providing access to cryoEM data collection capabilities to laboratories at participating regional (non-host) institutions will be funding considerations. 

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. 

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.

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 Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

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

The PD/PIs will manage the project and have authority over the project's budget.  Individual PD/PIs are responsible for abiding by and implementing decisions made by the group.  All investigators and institutions receiving funding through the project must abide by the provisions of the Multiple PD/PI Leadership Plan.  The PD/PIs will monitor performance in accordance with the scientific performance benchmarks in the Research Plan.  They should hold at least two official business meetings yearly.  These may be telephone conferences.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

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

NIGMS staff (a Project Coordinator and a Program Officer) have substantial programmatic involvement in oversight of project management.  The NIGMS Project Coordinator  is the Institute point-of-contact for the PD/PIs, except for special circumstances designated by NIGMS.  The Project Coordinator will attend all business meetings of the multi-PD/PI leadership team as a non-voting member and must be kept informed of all substantive deliberations and developments affecting the project.  The Project Coordinator will provide advice and guidance to ensure that the project adheres to the Research Plan and the Terms and Conditions of this award.  The Project Coordinator will keep the PD/PIs informed of any issues and concerns involving the project and provide advice on how to address them.

Additionally, an NIGMS Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice..

The Program Officer will monitor the project on an ongoing basis and will formally evaluate the project on a yearly basis.  The yearly evaluation will be based on the non-competing application and progress report and recommendations of the Project Coordinator.  NIGMS will review the performance and utilization of the resource.  NIGMS will also monitor that project is being managed in accordance with the Research Plan and the directives of the PD/PI Leadership Team.  NIGMS must approve in advance (i) changes to the roster of PD/PIs (ii) changes in the roster of participating laboratories, (iii) changes and exceptions to the Research Plan (including the Multiple PD/PI Leadership Plan and Sharing and IP Plans), (iv)changes in the scientific scope of the project, (v) changes to the frequency of business meetings.

Annual Review.  NIGMS will make a yearly determination whether the investigators are working together effectively and successfully as a team to conduct the project.  As a team, the PD/PIs are expected to consult with the participating laboratories and reach agreement about project management, including budgeting, personnel, and resource operations.  All participants are expected to abide by and support management decisions reached in accordance with the Multiple PD/PI Leadership Plan.  The Project Coordinator will consult yearly with the participating laboratories to assess performance.  If concerns are identified, the Program Coordinator will work with the PD/PIs to develop plans to address them in the next year of support.   If there are substantial changes in the roster or status of the participating laboratories, NIGMS may modify the budget and/or term of support.

Special Reviews.  NIGMS does not anticipate conducting special or mid-course reviews of scientific progress beyond the normal yearly non-competing progress review.  However, if concerns are identified about the performance of the resource or the management of the project, NIGMS may conduct special reviews of the project as it deems necessary.  NIGMS may engage outside experts to assist in these reviews.  If concerns about the project arise and are not resolved, NIGMS may reduce or restrict the budget or reduce the term of support to phase out the project.

The NIGMS Project Coordinator and the PD/PIs will monitor the technical performance of the resource and the delivery of services.  In the event of long-term incapacitation of resource facilities, NIGMS may reduce the budget and/or term of support to phase out the project.

Other Requirements.  All research publications supported by this grant must acknowledge its support by citing the grant number in the form "supported by NIGMS grant U24 GM000000".  The PD/PIs should maintain a current listing of all publications supported by the grant, which includes the exact acknowledgement of support that appears in the paper.  This list should also explain the contributions of this grant to the publication.

Areas of Joint Responsibility include:

Before the initial award is made, NIGMS and the awardees may negotiate clarifications, changes, or additions to the Research Plan.  Future changes to these plans may be made by the NIGMS and the PD/PIs.  Changes will be documented by an exchange of correspondence.

NIGMS and the PD/PIs will agree on scientific performance benchmarks prior to award and document these by an exchange of correspondence.  These may be adjusted later by mutual agreement.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the PD/PIs chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) and financial statements as required in the NIH Grants Policy Statement.

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. 

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

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: https://grants.nih.gov/support/index.html
Email: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-710-0267
Email: GrantsInfo@nih.gov

Paula Flicker, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-0828
Email: flickerp@nigms.nih.gov

Helen R. Sunshine, Ph.D.
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-2881
Email: sunshinh@nigms.nih.gov

Earl C. Melvin
National Institute of General Medical Sciences (NIGMS)
Telephone: 301-594-3912
Email: melvine@nigms.nih.gov

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 Parts 74 and 92.