Request for Information (RFI): Transformative High-Resolution Cryo-Electron Microscopy

Notice Number: NOT-RM-16-022

Key Dates
Release Date: June 24, 2016
Response Date: August 8, 2016  

Related Announcements

Issued by
Office of Strategic Coordination (Common Fund)


This is a Request for Information (RFI) to solicit input on a potential new Common Fund program aimed at accelerating the application of state-of-the-art cryo-electron microscopy (cryoEM) by the broad scientific community (


Recent technical advances in cryoEM have led to revolutionary improvements in image resolution and throughput, making it possible to solve macromolecular structures at or near atomic resolution.  Single particle cryoEM has unique capabilities for the study of a wide range of isolated macromolecules that are not accessible to other structural methods.  This method does not require crystallization and needs only small amounts of sample.  It can be used to determine the structures of complete and fully functional macromolecular complexes from approximately 175 kD upwards.  It has the potential to analyze compositionally and conformationally heterogeneous mixtures and, consequently, can be used to determine the structures of complexes in different functional states.  With further development, we anticipate that routine atomic resolution structure determination by single particle cryoEM will be possible.  A second application of cryoEM, cryo-electron tomography, can image macromolecular organization in intact cells.  This method has great potential but further technical development will be needed to realize its full capabilities.

Information Requested

This RFI solicits input from researchers, academic institutions, professional societies, businesses, not-for-profit organizations, other government agencies, and other stakeholders on scientific opportunities, critical needs, and strategies for realizing the scientific potential of cryoEM.  General suggestions on needs and strategies for improving the technology and facilitating the dissemination and use of CryoEM are welcome.  As such, comments may include, but are not limited to, the bulleted topics below.  When appropriate, please also include hyperlinks to pertinent references, databases, or other online resources.


  • Current access to and projected demand for state-of-the-art microscope facilities, for both currently practicing electron microscopists and for those intending to enter the field.
  • Expanding the scope of scientific applications of cryoEM.
  • Usefulness and current limitations of existing cryoEM research resources.
  • Needs and prioritization of research support/assistance and research services.
  • Advisability of community resources.  Configuration of resources and the services they should provide.  Evaluation criteria for community use of such resources.
  • Relative investment in infrastructure and personnel in the different steps of the cryoEM research pipeline (specimen preparation, screening, data collection, computational analysis).


  • The size of the current user base for cryoEM in the U.S.
  • The size of the potential user base for cryoEM in the U.S. in the next few years. 
  • Strategies for increasing the number of investigators able to make use of cryoEM.
  • Training needs and kinds of training needed.


  • Technical limitations of cryoEM instrumentation, methods, and software.  Priorities for technology development.
  • Current efforts to overcome these limitations.
  • Technical barriers specifically affecting application and capabilities of cryo-electron tomography.
  • Ways of decreasing the cost, increasing throughput, and improving the ease and reproducibility of cryoEM specimen preparation.

How to Submit a Response

Responses must be submitted via email to CRYOEM@MAIL.NIH.GOV by August 8, 2016.  

This RFI is for planning purposes only and should not be construed as a solicitation for applications or as an obligation on the part of the Government to provide support for any ideas identified in response to it. Please note that the United States Government will not pay for the preparation of any information submitted or for its use of that information.

The NIH will use the information submitted in response to this RFI at its discretion and will not provide comments to any responder's submission. Proprietary, classified, confidential, or sensitive information should not be included in your response.  The United States government reserves the right to use any non-proprietary technical information in any resultant solicitation(s). Responses to the RFI may be reflected in future funding opportunity announcements and will be used in the long-term planning for the Common Fund. Responses will be compiled and shared internally and with working groups convened by the NIH, as appropriate. In all cases where responses are shared, unless the respondent indicates otherwise, the names of the respondents will be withheld. We look forward to your input and hope that you will share this request with your colleagues.


Please direct all inquiries to:

Paula Flicker, Ph.D.
National Institute of General Medical Sciences
Telephone: 301-594-0828

Ravi Basavappa, Ph.D.
Office of Strategic Coordination/Office of the Director
National Institutes of Health