Sponsor Deadline
Posted: 4/18/2022

FIB-Milling Sample Preparation for Cellular CryoET

Single particle cryo-electron microscopy (Cryo-EM) has revolutionized structural biology, as recognized by the Nobel Prize in Chemistry in 2017. A limitation of single particle Cryo-EM, however, is that the molecule of interest must be separated from the cell, and thus it is removed from its natural environment. A breakthrough method, focused ion beam (FIB) milling of cellular samples, has been developed to overcome this limitation by cutting thin lamellas of cell interiors such that they are accessible to high-resolution cryo-electron tomography (Cryo-ET) imaging in situ. This breakthrough enables high-resolution 3-D structure determination for organelles and proteins in their natural environments.

A new technical challenge has emerged in being able to realize the full potential of FIB-milling by identifying exactly which cells in a large sample, and which organelles within these cells, are of particular interest to answering fundamental structural biology questions prior to FIB-milling of the sample. One solution to this problem is in the coupling of high-resolution cryogenic light microscopy techniques with FIB-milling in preparing cellular samples for Cryo-ET imaging.

The Arnold and Mabel Beckman Foundation’s mission is to support leading edge research, in the fields of chemistry and life sciences, and particularly to foster the invention of methods, instruments, and materials that open up new avenues of research and application in these sciences and related disciplines. In support of this mission, the Foundation is requesting proposals for a one-time grant opportunity for the procurement of cryogenic light microscopes, FIB-milling sample preparation equipment, appropriate Cryo-EM energy filters or detectors, and other freezing and grid preparation equipment as part of a larger cellular Cryo-ET workflow that will enable advanced research projects. In addition, applicants may include technology development efforts in one or more of the steps in the overall cellular Cryo-ET sample preparation workflow.

The Foundation will provide support of up to $1.5 million per Institution, which can be used flexibly for instrumentation acquisition, development, and maintenance; support for personnel, junior scientists and training programs; support for data science collaborations within the research teams; and/or costs for the proposed research programs. 

Eligibility Determination Submission Deadline: February 26, 2021 by 1 pm Pacific/4 pm Eastern

Eligibility submissions will be reviewed on a rolling basis. Eligible applicants will be provided access to the Full Proposal submission portal as soon as the review of their submission is complete, and no later than March 5, 2021.

Eligibility Requirements

The Foundation will consider proposals from individual institutions or from consortia of institutions whose combined resources will address the program requirements. For any consortium application, there must be a “Lead Institution”, defined as the institute that will maintain the purchased equipment on their property and will accept the entire grant award on behalf of the consortium. The Lead Institution submitting the proposal must be a nonprofit US university or research institution.

Universities or Institutions interested in applying must either already have the required cryo-electron tomography capability in place and operational, or have definitive plans to develop this capability in the near term (e.g. a commitment for a junior faculty hire in tomography), or have a track-record of successfully utilizing Cryo-EM Centers with tomography capabilities. The Foundation will require interested applicants to first complete an eligibility form in the online application system (https://beckman-foundation.smapply.io/) with the following questions:

  1. What are your current and/or planned near future capabilities in Cryo-ET instrumentation and personnel, and any existing FIB-Milling systems?
  2. Explain how your Institution will manage the additional instrument time requirements for this Cryo-ET program. If you will be utilizing a CryoEM Center for the final imaging, indicate which Center and briefly describe your history of coordinating with them.
  3. Provide a brief description of your planned research program that will be enabled by the addition of this instrumentation.

The Foundation will provide the Full Proposal documentation to applicants determined to be eligible for the program based on the responses above. Questions regarding eligibility can be directed to Anne Hultgren at InstrumentGrants@beckman-foundation.org. Decisions on eligibility by the Foundation will be final.

Funding Type