Cryo-CLEM Labels

About this funding opportunity

This RFA closed on July 20, 2023

SCIENCE GRANT RESOURCES PAGE Cryo-CLEM Labels RFA

The Chan Zuckerberg Initiative (CZI) seeks to support one-year projects in the field of cryo-correlative light and electron microscopy (cryo-CLEM) labels. To gain a deeper mechanistic understanding of biological systems, CZI’s Imaging program aims to visualize and measure them across biological scales and in their biological context. This Request for Applications (RFA) seeks to drive development of complete, general-purpose, intracellular imaging probes for cryo-CLEM. This grant program will advance the utility of cryo-electron tomography (cryo-ET) of cells by providing information on specific aspects of cell function.

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For administrative and programmatic inquiries, technical assistance, or other questions pertaining to this RFA, please contact sciencegrants@chanzuckerberg.com"). Key Dates

June 8, 2023

Application portal opens

July 20, 2023

Applications due by 5 p.m. Pacific Time

Late October 2023

Earliest notification of decisions (subject to change)

December 1, 2023

Expected start date (subject to change) Opportunity

Scope

This RFA will accelerate the development of imaging probes that can leverage and combine the strengths of 1) light microscopy to study cell function and 2) cryo-electron tomography to study sub-cellular structure. Development of genetically-encoded tags (green fluorescent protein, or GFP, and its variants), chemical tags (HaloTag, SNAP-tag), nanobodies, and other imaging labels have revolutionized live-cell and super-resolution fluorescence microscopy. In correlative light and electron microscopy (CLEM), registration of fluorescence microscopy with electron microscopy images can be used to identify specific structures or molecules, such as proteins, organelles, or other cellular components.

Recent advances in cryo-ET technologies have the potential to image the molecular architecture of the cell with atomic resolution. The field currently lacks a robust general-purpose label that is simultaneously visible by light and electron microscopy, can be directed to any intracellular protein of interest, and will only minimally perturb the assembly state or biological function of the targeted molecule. Visibility by cryo-ET is defined as detectable or computationally recognizable in unaveraged tomograms.

The long-term goal of this opportunity is to drive technology development aimed at visualizing intracellular structure and function using cryo-ET. We specifically seek proposals that support the development of intracellular imaging probes that can withstand cryogenic preservation, provide high photon yields to allow accurate localization in cryo-CLEM, and have sufficient electron contrast or a unique shape to be detectable in cryo tomograms. This funding opportunity is explicitly aimed at the design and demonstration of a complete solution for general-purpose, intracellular cryo-CLEM imaging probes that could be broadly disseminated to the cryo-CLEM/cryo-ET field.

Examples of potential areas within the scope of this RFA include, but are not limited to: Complete solution for cryo-CLEM labeling that includes high-yield fluorophores and features that are detectable in electron microscopy (EM), Genetically encoded fluorescent and electron-dense tags with unique shapes for cryo-CLEM, ideally self assembling only when attached to protein of interest, Carbon nanodots or chemically synthesized probes adapted for cryo-CLEM, Nanobody binders with unique shapes for cryo-CLEM, and AI and deep learning approaches to the design of cryo-CLEM labels.

Successful designs should be: Applicable to targets inside of intact cells, Kept as small as possible, Minimally perturbative of the structure or function of target protein, Visible at a single or low copy number by cryo fluorescence microscopy, Detectable in an unaveraged cryo-EM tomogram (either…

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

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

Cryo-CLEM Labels is administered by Chan Zuckerberg Initiative (CZI), listed via Chan Zuckerberg Initiative.