A supplement to: NIGMS 1R15GM144907-01A1 - Polymer-Lipid Particles investigated by Magnetic Resonance Spectroscopy

补充：NIGMS 1R15GM144907-01A1 - 通过磁共振波谱研究聚合物脂质颗粒

• 批准号: 10801755
• 负责人: Dominik Konkolewicz
• 金额: $ 9.96万
• 依托单位: MIAMI UNIVERSITY OXFORD
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10801755
• 关键词: Administrative Supplement; Binding Proteins; Biophysics; Calibration; Cell physiology; Cells; Charge; Clinical Trials; Complement; Detection; Development; Electron Spin Resonance Spectroscopy; Environment; Equipment; Evaluation; Funding; Gel Chromatography; Grant; Health; Hydrophobicity; Infection; Knowledge; Length; Lipid Bilayers; Lipids; Magnetic Resonance Spectroscopy; Maintenance; Measurement; Membrane; Membrane Lipids; Membrane Proteins; Mentors; Methods; Modernization; Molecular Weight; National Institute of General Medical Sciences; Parents; Polymer Chemistry; Polymers; Property; Proteins; Refractive Indices; Research; Secure; Services; Spin Labels; Structure; Structure-Activity Relationship; System; Techniques; Technology; Therapeutic; Training; U-Series Cooperative Agreements; United States National Institutes of Health; Virus Diseases; Work; amphiphilicity; analytical tool; cell growth regulation; cost; design; detector; graduate student; insight; instrument; lens; light scattering; materials science; mimetics; nanometer; nanoscale; novel; particle; protein complex; protein structure; repaired; response; self assembly; skills; structural biology; therapeutic development; tool; undergraduate student

A supplement to: NIGMS 1R15GM144907-01A1 - Polymer-Lipid Particles investigated by Magnetic Resonance Spectroscopy In response to: PA-20-272 - Administrative Supplements to Existing NIH Grants and Cooperative Agreements (Parent Admin Supp Clinical Trial Optional) Funds are requested from NIGMS to obtain state of the art gel permeation chromatography (GPC) multi-angle light scattering (MALS) equipment to facilitate polymer analysis. Development of novel polymers is integral to NIGMS 1R15GM144907- 01A1, therefore having reliable methods for characterizing the polymers is essential to the project. Funds are being requested to obtain a TOSOH EcoSEC Elite including Refractive Index and LenS3 Multi-Angle Light Scattering Detector GPC MALS system capable of efficient and accurate polymer analysis to replace equipment that is from 2014. Project Summary/Abstract: Membrane proteins represent approximately 30% of all known proteins but only approximately 1% of solved protein structures. Despite recent advances in methods for membrane protein structural biology, knowledge about this important class of proteins lags behind their soluble counterparts. Membrane proteins are critical to numerous aspects of health, ranging from regulation cellular function and transport into and out of the cell, through to viral infections which use membrane proteins as part of the infection cycle. In almost 90% of newly developed and approved therapeutics, protein structural information was used to guide the development of the therapeutic molecules. Due to the limited and incomplete structural information on membrane proteins, the development of therapeutics and treatments that target membrane bound proteins is limited. A challenge in elucidating membrane protein structures is the lack of robust and appropriate lipid membrane mimetics. Existing membrane mimetics have limitations that can hinder membrane protein structural determination. This highlights an urgent need to develop lipid membrane mimetics which both provide a good approximation to the native lipid bilayer in terms of both structure and curvature, while also facilitating structural analysis of the membrane protein embedded in the mimetic. Yet polymer structure-function relationships are not well established for polymers that interact with lipids and membrane proteins. This project will use modern controlled polymer chemistry tools, to create a new class of polymers that will self-assemble with lipids. These self-assembled polymer-lipid systems will form well defined discs on the order of 10s of nanometers, giving lipid membrane mimetics suitable for the analysis of many membrane proteins. The advanced polymer chemistry techniques will enable fine tuning of polymer’s length, charges, and hydrophobicity. Polymer analysis through GPC MALS will give detailed information on the polymer’s properties, facilitation structure -function relationships between polymers and their self-assembled structures. Polymers will also be modified with spin-labels for electron paramagnetic resonance spectroscopy. Electron paramagnetic resonance spectroscopy methods will be used on polymers, lipids and membrane proteins modified with appropriate spin labels, providing insights into the local dynamics and proximities of the self-assembled polymer-lipid and polymer-lipid-membrane protein complexes. These insights can be used to guide the design of polymers for robust lipid membrane mimetics. Training and mentoring of undergraduate students as well as a graduate assistant will be a core feature of the proposed project. Undergraduate students will be integrated fully into the projects, including the polymer analysis, along with the graduate student, gaining skills in this field at the interface of materials science and biophysics.

补充：NIGMS 1 R15 GM 144907 - 01 A1-聚合物-脂质颗粒 通过磁共振光谱研究 回应：PA-20-272 -现有NIH赠款的行政补充， 合作协议（家长管理支持临床试验可选） 要求NIGMS提供资金，以获得最先进的凝胶渗透技术 多角度光散射（MALS）设备，以便于 聚合物分析新型聚合物的开发是NIGMS 1 R15 GM 144907的组成部分- 01 A1，因此，具有用于表征聚合物的可靠方法对于 该项目正在申请资金以获得TOSOH EcoSEC Elite，包括 折射率和LenS 3多角度光散射检测器GPC MALS系统 能够高效准确地进行聚合物分析，以取代2014年的设备。 项目摘要/摘要：膜蛋白约占所有蛋白质的30%。 已知的蛋白质，但只有大约1%的解决蛋白质结构。尽管最近 膜蛋白结构生物学方法的进展， 一类重要的蛋白质滞后于它们的可溶性对应物。膜蛋白是 对健康的许多方面至关重要，从调节细胞功能， 运输进出细胞，通过使用膜蛋白的病毒感染 作为感染循环的一部分。在近90%的新开发和批准的 治疗学，蛋白质结构信息用于指导 治疗分子由于有限和不完整的结构信息， 膜蛋白，治疗和治疗的发展，目标 膜结合蛋白是有限的。阐明膜蛋白的挑战 结构的缺陷是缺乏稳健和适当的脂质膜模拟物。现有 膜模拟物具有可能阻碍膜蛋白结构的局限性 保持战略定力这突出了迫切需要开发脂质膜模拟物， 两者都提供了与天然脂质双层在两种结构方面的良好近似 和曲率，同时也有利于膜蛋白的结构分析 嵌入在模拟物中然而，聚合物的结构-功能关系并不好 建立了与脂质和膜蛋白相互作用的聚合物。 这个项目将使用现代可控高分子化学工具，创建一个新的类 能够与脂质自我组装的聚合物。这些自组装的聚合物-脂质 系统将形成10纳米量级的明确定义的盘， 膜模拟物适用于许多膜蛋白的分析。先进 聚合物化学技术将能够微调聚合物的长度，电荷， 疏水性通过GPC MALS进行的聚合物分析将提供有关聚合物的详细信息。 聚合物的性质，促进聚合物之间的结构-功能关系， 它们的自我组装结构。聚合物也将被修改与自旋标签， 电子顺磁共振谱电子顺磁共振 光谱方法将用于聚合物，脂质和膜蛋白修饰 与适当的自旋标签，提供深入了解当地的动态和邻近的 自组装聚合物-脂质和聚合物-脂质-膜蛋白复合物。这些 这些见解可用于指导用于稳健脂质膜模拟物的聚合物的设计。 培训和指导本科生以及研究生助理将 成为项目的核心特征。本科生将全面融入 进入项目，包括聚合物分析，沿着与研究生，获得 在材料科学和生物物理学的界面上的这一领域的技能。