CAREER: Enabling nanodisc native mass spectrometry to study membrane active compounds

职业：利用纳米盘原生质谱来研究膜活性化合物

• 批准号: 1845230
• 负责人: Michael Marty
• 金额: $ 75万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1845230&HistoricalAwards=false
• 关键词: CAREER; Enabling; nanodisc; native; mass

Cells within the human body are consistently under attack by invaders, which include bacteria, viruses, and certain molecules in the environment. While it is known that membrane-active compounds (MACs) defend human cells by interacting with the invader's cell membranes, exactly how they do this is still unclear. Dr. Michael Marty of the University of Arizona uses mass spectrometry to gain an understanding of membrane-active compound behavior and thus, provides fundamental insight into how the body's immune system functions. This project uses new mass spectrometry tools to determine how MACs change the structure and stability of cell membrane mimics. A set of integrated educational activities provide professional training in mass spectrometry data analysis while engaging military veterans in science education and research activities. The program eases the transition of veterans from military service to higher education, promotes persistence in STEM education (STEM), and broadens participation in research. Tutorials are also created to enhance the educational infrastructure and broaden the dissemination of data analysis technologies.With this award, the Chemistry of Life Processes Program, with co-funding from the Chemical Measurement and Imaging Program, is funding Dr. Michael Marty at the University of Arizona to study membrane-active compounds (MACs) that directly target lipid membranes. In the past, these mechanisms of action were not well understood because it is difficult to quantify MAC interactions within membranes. Dr. Marty is addressing this challenge through the development of novel chemical measurement techniques based on native mass spectrometry (MS) methods and lipoprotein nanodisc membrane mimetics. By measuring the mass of the entire nanodisc assembly with embedded MAC complexes, it is possible to characterize the oligomeric states of MACs in different lipid environments. This CAREER project provides the foundation for these experiments by uncovering the mechanisms of nanodisc stability under native MS conditions, creating native MS-compatible nanodiscs that model natural membranes, and developing algorithms for the analysis of complex MS data. The research objectives are integrated with two educational objectives that involve the engagement of undergraduate military veterans in STEM research and the development of professional education tutorials.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

人体内部的细胞一直受到入侵者的攻击，其中包括细菌，病毒和环境中的某些分子。虽然众所周知，膜活性化合物（MAC）通过与入侵者的细胞膜相互作用来捍卫人类细胞，但尚不清楚它们的工作方式仍然不清楚。亚利桑那大学的迈克尔·马蒂（Michael Marty）博士使用质谱法来了解膜活性复合行为，因此提供了对人体免疫系统如何发挥作用的基本见解。该项目使用新的质谱工具来确定MAC如何改变细胞膜模拟的结构和稳定性。一系列综合教育活动提供了质谱数据分析的专业培训，同时让退伍军人参与科学教育和研究活动。该计划减轻了退伍军人从兵役到高等教育的过渡，促进STEM教育（STEM）的持久性并扩大了研究的参与。还创建了教程，以增强教育基础架构并扩大数据分析技术的传播。该奖项与化学过程计划的化学计划，并从化学测量和成像计划中获得了共同资助，正在为亚利桑那大学的迈克尔·马蒂（Michael Marty）提供资金，以研究亚利桑那大学的迈克尔·马蒂（Michael Marty），以研究膜活性化合物（MACS）对目标lipid embranses进行了目标。 过去，这些作用机理尚不清楚，因为很难量化膜内的MAC相互作用。 Marty博士通过基于天然质谱法（MS）方法和脂蛋白纳米盘膜模拟物的新型化学测量技术来应对这一挑战。通过用嵌入式MAC复合物测量整个纳米轴组件的质量，可以在不同脂质环境中表征MAC的低聚状态。该职业项目为这些实验提供了基础，通过在本机MS条件下发现纳米轴稳定性的机制，从而创建了与自然膜建模的本机MS兼容的纳米盘，并开发了用于分析复杂MS数据的算法。研究目标与两个教育目标融合在一起，涉及本科退伍军人参与STEM研究和专业教育教程的发展。该奖项反映了NSF的法定任务，并被认为值得通过基金会的知识分子优点和更广泛的审查标准通过评估来进行评估。

项目成果

Stability and Dissociation of Adeno-Associated Viral Capsids by Variable Temperature-Charge Detection-Mass Spectrometry

• DOI: 10.1021/acs.analchem.2c02378
• 发表时间: 2022-08-18
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Kostelic, Marius M.;Ryan, Jack P.;Marty, Michael T.
• 通讯作者: Marty, Michael T.

Nanodiscs and mass spectrometry: Making membranes fly

• DOI: 10.1016/j.ijms.2020.116436
• 发表时间: 2020-12-01
• 期刊: INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
• 影响因子: 1.8
• 作者: Marty, Michael T.

Eliminating Artifacts in Electrospray Deconvolution with a SoftMax Function

• DOI: 10.1007/s13361-019-02286-4
• 发表时间: 2019-10-01
• 期刊: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY
• 影响因子: 3.2
• 作者: Marty, Michael T.

Native Mass Spectrometry of Antimicrobial Peptides in Lipid Nanodiscs Elucidates Complex Assembly

• DOI: 10.1021/acs.analchem.9b02261
• 发表时间: 2019-07-16
• 期刊: ANALYTICAL CHEMISTRY
• 影响因子: 7.4
• 作者: Walker, Lawrence R.;Marzluff, Elaine M.;Marty, Michael T.
• 通讯作者: Marty, Michael T.

Fourier-Transform Approach for Reconstructing Macromolecular Mass Defect Profiles

重建大分子质量缺陷轮廓的傅里叶变换方法

• DOI: 10.1021/jasms.1c00317
• 发表时间: 2022
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Swansiger, Andrew K.;Marty, Michael T.;Prell, James S.
• 通讯作者: Prell, James S.