# New cryo-EM methods to visualize ribosome heterogeneity at single molecule resolution in cells

> **NIH NIH DP2** · UNIVERSITY OF CALIFORNIA BERKELEY · 2024 · $1,444,500

## Abstract

PROJECT SUMMARY
Cryogenic electron microscopy can generate atomic resolution views of cells and is therefore a promising
technology to study the molecular mechanisms underlying key cellular processes in cells. However, cryo-EM
images cannot be interpreted directly to atomic resolution because cryo-EM imaging introduces radiation
damage to biological macromolecules. Current strategies to address radiation damage require combining
multiple copies to generate a single 3D reconstruction representing an average of the individual molecules. This
not suitable for cellular imaging because only a select few macromolecules are present in sufficiently high
numbers to generate an interpretable average. As a postdoc I contributed to the development of an alternate,
single molecule strategy to characterize the structure, interactions, and organization of macromolecular
complexes in cryo-EM images called 2D template matching (2DTM). Since 2DTM does not require averaging, it
has the potential to simultaneously visualize all cellular complexes individually, presenting a potentially
revolutionary new understanding of cellular function in health and disease. However, the potential of 2DTM is
currently limited by the difficulty to localize smaller complexes. With support from the NIH New Innovators
Program, I will pursue new strategies to extend 2DTM to detect and characterize smaller structures. New
technologies, particularly new imaging technologies, open new avenues of research because they allow us to
ask questions and see things that were never previously possible. Opening the cell to visualization at the
resolution of individual macromolecules will undoubtably reveal new, previously unanticipated biology.

## Key facts

- **NIH application ID:** 10910792
- **Project number:** 1DP2GM159184-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Bronwyn Ayla Lucas
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,444,500
- **Award type:** 1
- **Project period:** 2024-09-02 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10910792

## Citation

> US National Institutes of Health, RePORTER application 10910792, New cryo-EM methods to visualize ribosome heterogeneity at single molecule resolution in cells (1DP2GM159184-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10910792. Licensed CC0.

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