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Expanding the Scope of NMR Sample Preparation

扩大 NMR 样品制备的范围

基本信息

批准号：
10573324
负责人：
Katherine Anne Henzler-Wildman
金额：
$ 18.74万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-02 至 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10573324
关键词：
Activities of Daily Living Aphorisms Benchmarking Biological Cell Membrane Permeability Cells Characteristics Chemicals Data Collection Disease Drug Targeting Ensure Environment Formulation Goals Hour Hydration status Individual Integral Membrane Protein Investments Ionic Strengths Ions Isotope Labeling Knowledge Label Ligands Light Lipid Bilayers Lipids Liposomes Magic Measurement Measures Membrane Membrane Potentials Membrane Proteins Methods Micelles Molecular Weight Nuclear Persons Pharmaceutical Preparations Phase Physiologic pulse Physiological Preparation Process Proton-Motive Force Recycling Relaxation Reproducibility Resolution Resources Sampling Scientist Series Solid Specific qualifier value Structure Techniques Technology Time Titrations Training Tube Viscosity Work biophysical properties biophysical techniques computerized tools cost cryogenics data acquisition design experimental study instrument macromolecule magnetic field milligram nanodisk pH gradient protein function risk mitigation sensor small molecule solid state solid state nuclear magnetic resonance solute structural biology success synergism technology research and development tool voltage wasting

项目摘要

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.

Tr&d 1总结