# Expanding the Scope of NMR Sample Preparation

> **NIH NIH P41** · UNIVERSITY OF WISCONSIN-MADISON · 2021 · $206,355

## Abstract

TR&D 1 SUMMARY
This technology research and development project targets two major challenges for solid-state NMR and
structural biology. First, sample handling represents a major bottleneck for solid-state NMR, costing time,
money, and wasted sample. Powerful new solid-state NMR relax the volume and labeling requirements, but
only if precious biological samples can be efficiently transferred into tiny MAS rotors. We will develop tools to
make this process faster, more efficient and reliable. We will also develop tools to change sample conditions in
the MAS rotor to better assess the functional state of a sample during experiments. Second, membrane
proteins function in an asymmetric environment in the presence of transmembrane gradients of voltage, ions,
and pH, but structural biology of membrane proteins is carried out in the absence of these gradients. This
makes it difficult to correlate structure with function and creates one of the largest current knowledge gaps in
structural biology. The project develops technology to perform NMR studies of membrane proteins embedded
in lipid bilayers in the presence of transmembrane voltage, pH and ion gradients using several different
approaches to ensure gradient stability during NMR data collection. We will also develop NMR-readout
sensors to measure the membrane potential and pH and ion gradients during NMR data acquisition. This
technology will enable direct measurement of the structure and dynamics of membrane proteins in the
presence of gradients, revealing how transmembrane gradients regulate and drive membrane protein function.
Since a large percentage of drug targets are membrane proteins that create, transform, dissipate or are
regulated by transmembrane gradients, this technology will have high biomedical impact.

## Key facts

- **NIH application ID:** 10089600
- **Project number:** 1P41GM136463-01A1
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **Principal Investigator:** Katherine Anne Henzler-Wildman
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $206,355
- **Award type:** 1
- **Project period:** 2021-01-02 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10089600

## Citation

> US National Institutes of Health, RePORTER application 10089600, Expanding the Scope of NMR Sample Preparation (1P41GM136463-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10089600. Licensed CC0.

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