# MEDIC - MicroED Imaging Center at UCLA

> **NIH NIH P41** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $2,415,437

## Abstract

MEDIC – MicroED Imaging Center at UCLA
Project Summary
We are proposing to establish a national resource at UCLA for the development, training and dissemination of
advanced electron diffraction technologies. Cryo-electron microscopy (cryoEM) methods promise new life to
high-throughput macromolecular structure determination. CryoEM overcomes the fundamental barrier to X-ray
diffraction determination of macromolecular complexes: growing X-ray grade crystals. Fortunately, the
emergence of microcrystal electron diffraction (MicroED) facilitates the determination of new protein structures
at atomic resolution from vanishingly small crystals. MicroED exploits the strong interaction between electrons
and nano-scale three-dimensional crystals and takes advantage of emerging cryoEM instrumentation coupled
to established crystallographic methods. We pioneered MicroED to achieve milestone discoveries, namely we
determined previously unknown protein structures at atomic resolution from crystals smaller than the wavelength
of visible light. 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 of new and more efficient approaches to structure determination by MicroED opens 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. Our
proposed innovations to technology development in MicroED are in four categories: (1) improved sample
screening and preparation, (2) novel refinement and phasing methods, (2) demonstrating the applicability of
MicroED to natural products and small molecules, and (4) engineering new hardware for investigating structure
dynamics in real time. The biomedical problems associated with these types of assemblies are broad and impact
biomedicine, both through the basic understanding of disease and through enabling new therapeutic platforms.
Our group of key personnel brings together expertise from all modalities of cryoEM, crystallography,
biochemistry, molecular biology, and computation to help develop the next generation of MicroED tools. This
effort will be informed by projects led by expert groups around the country working on projects that pose
significant structural challenges. Together, we propose a resource that can make nanocrystallography and
MicroED routine methodologies for non-experts. Extensive user training and community engagement will further
disseminate the MicroED technology and bring new structures to light.

## Key facts

- **NIH application ID:** 9935721
- **Project number:** 1P41GM136508-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Tamir Gonen
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $2,415,437
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9935721

## Citation

> US National Institutes of Health, RePORTER application 9935721, MEDIC - MicroED Imaging Center at UCLA (1P41GM136508-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9935721. Licensed CC0.

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