FIB-Milling Sample Preparation for Cellular CryoET

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In situ cryo-electron tomography reveals the molecular architecture of the Chlamydomonas Golgi apparatus with native morphology. Data courtesy of Dr. Benjamin Engel, Helmholz Munich. Image courtesy of ThermoFisher Scientific.

In situ cryo-electron tomography reveals the molecular architecture of the Chlamydomonas Golgi apparatus with native morphology. Data courtesy of Dr. Benjamin Engel, Helmholz Munich. Image courtesy of ThermoFisher Scientific.

Info FIB-Milling Sample Preparation for Cellular CryoET

Information:

This program is closed for new applications.

Link to Request for Proposals

Request for Proposals:

FIB Milling Cryo-ET RFP_Final.pdf

Program Summary

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. Applicant institution(s) must demonstrate their commitment for additional funding beyond the $1.5 million support from the Arnold and Mabel Beckman Foundation, if necessary, to complete the objectives of the program described below. Additional information on the institutional support requirements can be found in the template in the online application portal.

Program Objectives

Proposals should be centered around core biological problems and a research program that is enabled by the high-resolution, in-situ imaging capabilities of the cryogenic light microscopy guided FIB-milling for cryo-electron tomography of cellular interiors. Additional consideration will be given to proposals that include other imaging, sensing, or analysis technologies as an integral part of one or more of the proposed research project(s). Applicants shall identify the…

Topic areas: Life Sciences and Health, General and Cross-cutting R&D, Physical Sciences.

Funding amount

This grant provides Varies in funding.

Deadline

Applications are accepted on a rolling basis; there is no single fixed deadline.

Who can apply

This opportunity is open to the following applicant types:

• Not specified by the program.

Eligibility

The program did not publish a separate eligibility statement. See the official opportunity page for the full eligibility criteria.

Agency

FIB-Milling Sample Preparation for Cellular CryoET is administered by Arnold and Mabel Beckman Foundation (Beckman), listed via Arnold and Mabel Beckman Foundation.