Regional Consortia for High-Resolution Cryoelectron Microscopy (U24) Guidance for Applicants

This guidance is intended to assist potential applicants in understanding the intent and requirements of RFA-GM-17-005, Regional Consortia for High Resolution Cryoelectron Microscopy (U24).


Q. What is the purpose of this RFA?

A. The purpose of this funding opportunity announcement (FOA) is to provide regional access to state-of-the-art data collection capabilities to cryoelectron microscopy (cryoEM) laboratories. For this FOA, a cryoEM laboratory is defined as a laboratory with an established, independent specialization in and dependence on cryoEM.

Q. Why is this FOA restricted to cryoEM laboratories?

A. Because funds are limited, this FOA is a short-term initiative of limited scope that addresses a specific, immediate problem of research access for laboratories whose research programs are dependent on cryoEM.

Q. What are the components of a consortium?

A. Consortia consist of a Host Institution and Partner Institutions. At each Partner Institution there may be one or more partner laboratories, each headed by a Partner Investigator.

Q. What is a Host Institution?

A. The Host Institution operates a cryoEM facility used by the Partner Institutions for cryoEM data collection. The Host Institution should already have a modern, high-performing cryoEM installation and proven capability for high-resolution data collection. The Host Institution should have sufficient capacity to accommodate the data collection needs not only of its own laboratories, but those of the consortium users as well. The Host Institution is represented by one PD/PI on the leadership team.

Q. What is a Partner Institution?

A. A Partner (non-host) Institution has one or more participating partner cryoEM laboratories and is represented by one PD/PI on the leadership team. There may be more than one partner cryoEM laboratory at a Partner Institution. The Host Institution is not a Partner Institution, and laboratories at the Host Institution are not partner laboratories.

Q. What is a Partner Investigator?

A. A Partner Investigator is the head of an independent cryoEM laboratory at a Partner Institution who is listed in the application and will be supported by the consortium. Note that investigators at the Host Institution, even if they are involved with the project, are not Partner Investigators.

Q. My cryoEM laboratory is at the Host Institution. What role can I play in a consortium?

A. You may be involved with and have effort on the project, but will not be a Partner Investigator. Along with other laboratories at the host site, you may manage personnel or resources that are supported by a consortium award.

Eligible Laboratories

Q. My laboratory uses cryoEM. Am I eligible to participate as a Partner Investigator?

A. Consult with the scientific contact listed in the FOA. Both new and established investigators are eligible.  Criteria are a record of independent cryoEM research (independent cryoEM publications and grants for established investigators and cryoEM publications for new investigators).  Your laboratory should have a publication record documenting its dependence on cryoEM as an essential part of its research program.

Q. My laboratory collaborates with an established cryoEM laboratory. Am I eligible to participate as a Partner Investigator?

A. Not directly. However, your cryoEM collaborator may be eligible to participate. This would provide access to facilities for your collaborative research efforts.

Q. My laboratory plans to adopt cryoEM as a major specialization. Am I eligible to participate?

A. No. Because funds are limited, this FOA is restricted to support of investigators whose laboratories have an established, independent record of specialization in and dependence on cryoEM. The FOA is not designed to support new users in adopting cryoEM. NIH will address the larger question of broader access to cryoEM in a recently published Common Fund initiative (RFA-RM-17-002).

Q. My laboratory has a high-performing cryoEM installation and proven capability for high-resolution data collection, but does not have a direct electron detector. Am I qualified to be a host laboratory?

A. Yes, you are qualified. You may request funding for direct electron detection equipment. Other equipment for state-of-the-art data collection capabilities that are relevant to the needs of the consortium Partner Investigators may also be requested. In the application, you should describe the financial arrangements for acquiring the necessary equipment.

Q. Our team is expert in cryoEM but does not have prior experience with electron detectors and preliminary data from electron detectors. Can we apply?

A. Yes, if you have the necessary skills to implement the technology. Previous experience and preliminary data are not required. In the application, your team should document its general qualifications and other experience relevant to adopting direct electron detection technology. In addition to expertise in cryoEM data collection, NIGMS anticipates that peer reviewers will be looking for expertise in computation, which is critical for direct detection. Teams lacking experience with direct electron detection may choose to enlist expert consultants who can provide technical assistance, which may help address potential reviewer concerns about gaps in technical expertise.

Q. My institution is foreign. Can I apply?

A. No. See Section III. Eligibility Information. Non-domestic (non-U.S.) entities are not eligible to apply. However, foreign components (defined in the NIH Grants Policy Statement link in the FOA) are allowed.

Q. My site is already supported by an existing cryoEM resource grant. Am I eligible to apply as a host site?

A. Yes, if you have surplus capacity available to dedicate to a consortium. PD/PIs of existing centers and research resources, including, for example, NIH Biotechnology Research Resource (BTRR) P41 investigators, may apply. The applications should explain the technical/logistical relationship between consortium and other activities at the host site and address any concerns about conflicting priorities.

Q. I do not have an NIH grant. Am I eligible to apply?

A. Yes, cryoEM investigators who are not NIH or NIGMS grantees may apply to this FOA. However, your research should be within the broad biomedical research mission of NIH.

Q. I am new investigator. Am I eligible to apply?

A. Yes, if your research has an established specialization in and dependence on cryoEM, you may apply.

Activities Supported by Consortium Awards

Q. What is the purpose of a consortium award?

A. These consortium awards provide support for excess capacity for cryoEM data collection (infrastructure and services) at the Host Institution and make it available to the participating Partner Institutions.

Q. What research does this consortium award support?

A. The only activity supported by these consortium awards is cryoEM data collection and initial processing by the partner laboratories. The awards do not support other stages of cryoEM analysis. Unlike many resource grants, these awards do not directly support research applications or technology development.

Q. How is consortium funding divided between host and Partner Institutions?

A. Consortium funding contributes to the fixed costs of maintaining the host facility and extends services in proportion to the resources dedicated to the partners. That is, consortium awards support the capacity at the host site that is dedicated to the partners. Awards may also support the expenses of partners to access the host facility, for example travel, lodging and laboratory facilities.

Q. What support do consortium awards provide for laboratories at the Host Institution?

A. Consortium awards do not support laboratories at the Host Institution. The purpose of consortia is to allow host sites to make surplus data collection capacity available to the partner laboratories. Benefits to the Host Institution are indirect.

Q. Since consortia support only the Partner Investigators, what is the advantage of hosting a regional consortium?

A. This funding opportunity would benefit Host Institutions that have excess capacity for cryoEM data collection and need partners to share expenses for infrastructure. For an institution that has full financial support for its infrastructure, there is no financial advantage in hosting a consortium. However, in many cases, cost sharing with a consortium would enable a Host Institution to support better infrastructure and services than it could afford without a partner. In addition to the advantages of proximity, there are also intangible intellectual benefits in teaming with partners.

Q. May we request funds for research, for example technology development to improve direct detection technology?

A. No. Applications must focus on providing infrastructure, access and services for data collection to the partner laboratories, and must NOT include other research activities. Applications requesting support for activities outside the scope and purpose of the FOA may be returned to applicants without review.

Q. How do these consortia compare to other NIH resource and center grants?

A. They are very different in many respects. Potential applicants should not make assumptions about this FOA based on experience with other NIH resource and center grants.

Q. When should I include a description of research conducted by laboratories at the Host Institution?

A. Only when documenting technical qualifications to host a consortium, or when the research is directly relevant to providing infrastructure, access and services for data collection to the partner laboratories. In deciding what to include in the application, keep in mind that the purpose of the FOA is to support data collection by the partner laboratories, not by laboratories at the Host Institution.

Q. Can we support a person at the Host Institution to collect cryoEM data for the partner laboratories?

A. Yes, this is an option. The FOA does not specify how grantees will organize or operate their resources.

Q. Can partner laboratories mail in their specimens for data collection by consortium personnel at the host site?

A. Yes, this approach is an option.

Multiple PD/PI Project Leadership Team

Q. Who directs a consortium?

A. A consortium is led by a team of PD/PIs, one from each Partner Institution and one from the Host Institution. Each PD/PI should be the head of a cryoEM laboratory.

Q. What is the relationship between the PD/PIs and the partner laboratories?

A. There may be more than one cryoEM laboratory per institution, but the Partner Investigators at each institution are represented by only one PD/PI on the multiple PD/PI leadership team.

Q. Two laboratories at our Host Institution jointly operate the cryoEM facilities. May both of their lead investigators be PD/PIs on a consortium?

A. No. One PD/PI must represent the interests of all the scientific stakeholders at the Host Institution.

Q. Two laboratories at our partner (i.e. non-host) institution would participate in a consortium. May both of their lead investigators be PD/PIs?

A. No. One PD/PI must represent the interests of both.

Q. Can I apply as a PD/PI or Partner Investigator on more than one application to this FOA?

A. Yes. Investigators may participate in more than one application to this FOA. The rosters of laboratories supported by the consortia that are ultimately funded through this FOA may overlap, since NIGMS aims to achieve some redundancy of coverage to ensure uninterrupted ability to collect data. After the best qualified consortia are identified through the review and awards process, NIGMS staff will resolve any coverage issues.

Q. Can we include co-PIs?

A. No. The role of "Co-PI" is not recognized by this FOA or by NIH. Applicants are asked not to use "Co-PI", "Co-investigator", "Co-director", or variations on these titles that imply a PD/PI-like role. Project roles like "Facility Director" or "Manager" are acceptable for persons who will direct day-to-day operations but will not have a PI/PD role.

Preparing an Application

Q. Why is it important to read the entire FOA?

A. Information and instructions that are specific to this FOA are located in several locations in the announcement. Information specific to this FOA is not necessarily marked to distinguish it from surrounding standard text. Certain essential items of information and instructions appear only once within the FOA.

Q. What sections of the FOA contain critical, FOA-specific application information?

A. All sections. Read the entire FOA carefully. FOA-specific information includes, but is NOT limited to:

RFA Section I. Funding Opportunity Description. This section explains the scope and purpose of the FOA.

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

RFA Section III. Eligibility Information. Subsection 1. Eligible Applicants - Eligible Individuals (PD/PI). Along with standard information, this subsection contains critical FOA-specific information about PD/PI eligibility.

RFA Section IV. Application and Submission Information. Section 2. Content and Form of the Application Submission. In addition to important standard instructions, these sections also contain FOA-specific application instructions:
(i) SF424 (R&R) Other Project Information - Facilities & Other Resources Attachment
(ii) SF424 (R&R) Senior/Key Person Profile
(iii) R&R Budget
(iv) PHS398 Research Plan - Research Strategy, Multiple PD/PI Leadership Plan, Resource Sharing Plan, Appendix

RFA Section V. Application Review Information. Subsection 1. Criteria. The introductory paragraph contains critical FOA-specific review criteria. The Significance, Investigator(s), Innovation, Approach and Environment criteria all contain FOA-specific review questions.

RFA Section VI. Award Administration Information. Subsection 2. Cooperative Agreement Terms and Conditions of Award.

Q. What are the page limits?

A. This FOA specifies no exceptions to the NIH standard page limits. Refer to the Table of Page Limits website. If a page limit is not specified for a section (for example, Multiple PD/PI Leadership Plan, Resource Sharing Plan), there is no page limit.

Specifying Personnel

Q. How do we identify the PD/PIs for the consortium?

A. Applications must be multiple PD/PI applications. Each PD/PI must be assigned the "PD/PI" role in accordance with the instructions in the SF424 application guide, Section 4.5. Senior/Key Person Profile Expanded Component. Note that the PD/PIs on the application must be registered in the Commons and hold PI accounts.

Q. Is there any other way to identify PD/PIs?

A. No. PD/PIs must be identified by the PD/PI role. Assigning an individual the title of "Co-PI," "Co-PD/PI" or "Co-Investigator" will not identify the application as a multiple PD/PI application or identify the individual as a PD/PI.

Q. How do we list Partner Investigators in the Senior/Key Personnel Section?

A. There are two ways: (a) Partner Investigators who are PDs/PIs should be assigned the PD/PI role in the Project Role Field. (b) Partner Investigators who are not a PDs/PIs should be identified as "Other” in the Project Role field and “Partner Investigator” in the “Other Project Role Category.” Note that Partner Investigators must have effort committed to the project.

A biosketch must be included for Partner Investigators. The first sentence of the biosketch should identify the individual as a "Partner cryoEM Investigator." The biosketches must include his/her qualifications for membership in the consortium, referencing recent publications and grant support relevant to cryoEM.

Q. How do we identify other persons working on the project?

A. Persons who are not Partner Investigators should only be included in Senior/Key Personnel if they are committing measurable effort and have an essential role in the project that is described in the application. They should be identified as "Other” for the Project Role field. In the “Other Project Role Category” they should be identified with roles such as "Expert", "Collaborator", or "Consultant" that clearly distinguish them from the Partner Investigators. A biosketch must be included.

Q. Is a commitment of effort required for Key Personnel?

A. Yes. All persons listed in Senior/Key Personnel must have effort committed to the project.

Q. How can I include persons who are not committing effort to the project in the application?

A. Persons who are not committing effort to the project should not be included in the Senior/Key Personnel but letters of support from these individuals may be included and they may be referenced in the Research Strategy. For example, cryoEM experts at the Host Institution who will be available for consultation but have no effort or specific role in the project should not be listed in Senior/Key personnel but may be included in Letters of Support.

Q. How do I identify support personnel?

A. Support personnel may be included in the budget justification but should not be listed in Senior/Key Personnel.

Multiple PD/PI Leadership Plan

Q. Why is the leadership plan important?

A. 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 applicants devise a robust and workable management scheme and describe it clearly and completely. Project management will be an important consideration in peer review and selection for funding. Useful guidance for the management of projects by multiple investigators is posted on the NIH Multiple PD/PI Web page. Potential applicants are encouraged to consult the Institute scientific contact listed in Section VI about their project management plans.

Q.What should we address in our leadership plan?

A. Follow both the general and FOA-specific instructions (Section IV. Subsection 2) for the Multiple PD/PI Leadership Plan. All participants (including PD/PIs and Partner Investigators) should agree in advance on their management plans and describe fully how the project will be governed. Plans should include mechanisms for making decisions and for resolving disagreements. This FOA uses an NIH cooperative agreement funding mechanism; applicants should refer to Part 2, Section VI.2 of this FOA, "Cooperative Agreement Terms and Conditions of Award," and make sure that their leadership plans are consistent with that section.

Q. Where do we describe our leadership plan?

A. Project management by the PD/PIs should be described in the Multiple PD/PI Leadership Plan section of the SF424. The Leadership Plan is a separate section from the Research Strategy and is not included in the page limit for the Research Strategy.

Q. We have more than one partner laboratory at some of our institutions, but only one PD/PI per institution is allowed. How are the other laboratories represented?

A. Partner Investigators should work out agreements in advance about how their interests will be represented in project management and explain them in the Multiple PD/PI Leadership Plan.