# Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies

> **NIH NIH R35** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2021 · $371,577

## Abstract

PROJECT SUMMARY
Despite modern advances in structural biology, structures of many biomedically relevant
macromolecular assemblies remain out of reach or lack atomic resolution detail. In addition, the
process of determining entirely novel structures remains laborious. Large crystals required for
conventional crystallography experiments are a challenge to grow, and determination of
structures from small or imperfect crystals by x-ray crystallography remains limited. Cryo-
electron microscopy (cryo-EM) methods promise to bring new life to high-throughput
approaches in macromolecular structure determination. The cryo-EM revolution has brought
with it new high-resolution methods including micro electron diffraction (MicroED). MicroED
exploits the strong interaction between electrons and nano-scale three-dimensional crystals by
leveraging emerging cryo-EM instrumentation against established crystallographic knowledge.
My group has helped achieve milestone discoveries in MicroED and determined entirely new
protein structures from crystals and crystal fragments smaller than the wavelength of visible
light, at atomic resolution. These technological advances, coupled with the greater availability of
advanced cryoEM instruments, present an opportunity for further improvement of high-
throughput structure determination. The development new and more efficient approaches to
structure determination by MicroED could open new avenues for comprehensive exploration of
complex macromolecular structures that remain out of reach for standard methods. These
systems include macromolecular complexes that grow small, fragile, or imperfect crystals. The
biomedical problems associated with these types of assemblies are varied and could broadly
impact biomedicine, both through the basic interpretation of disease and as therapeutic
platforms. Specifically, we aim to target infectious and/or toxic filamentous nanoassemblies
associated with amyloid disease. Through our efforts in determining these challenging
structures, we find inspiration to guide the improvement and development of cryoEM
techniques, particularly MicroED. With this goal in mind, my group will take on the development
of new high-throughput methods for crystallographic structure determination while obtaining
structures of pressing biomedical targets at truly atomic resolution.

## Key facts

- **NIH application ID:** 10219307
- **Project number:** 5R35GM128867-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jose Alfonso Rodriguez
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $371,577
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10219307

## Citation

> US National Institutes of Health, RePORTER application 10219307, Micro Electron Diffraction of Toxic and/or Infectious Macromolecular Nanoassemblies (5R35GM128867-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10219307. Licensed CC0.

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