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.

：NIGMS 1R15GM144907-01A1-聚合物脂质颗粒的补充 通过磁共振光谱研究 响应：PA-20-272-现有NIH赠款的行政补品以及 合作协议（家长管理员支持临床试验可选） 从Nigms要求资金获得最先进的凝胶渗透状态 色谱（GPC）多角度光散射（MALS）设备以促进 聚合物分析。新型聚合物的开发与斑点15GM144907-不可或缺 01a1，因此具有表征聚合物的可靠方法对于 项目。要求资金获得Tosoh Ecosec Elite，包括 折射率和镜头3多角度散射检测器GPC MALS系统 能够有效，准确的聚合物分析以取代2014年以来的设备。 项目摘要/摘要：膜蛋白约占所有的30％ 已知蛋白质，但仅约1％的溶液蛋白质结构。尽管最近 膜蛋白结构生物学方法的进步，知道这一点 重要类别的蛋白质落在其固体对应物后面。膜蛋白是 对健康的许多方面至关重要，从调节细胞功能和 传输到使用膜蛋白的病毒感染进入细胞和流入细胞 作为感染周期的一部分。在几乎90％的新开发和批准中 治疗，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，靶向的理论和治疗的发展 膜结合蛋白是有限的。阐明膜蛋白的挑战 结构是缺乏健壮且适当的脂质膜模拟物。现存的 膜模拟物具有可能阻碍膜蛋白结构的局限性 决心。这凸显了迫切需要开发脂质膜模拟物 两者都可以就两种结构而言，都可以与天然脂质双层 和曲率，同时还支持膜蛋白的结构分析 嵌入模拟物中。但是聚合物结构功能关系不好 为与脂质和膜蛋白相互作用的聚合物建立。 该项目将使用现代受控聚合物化学工具来创建新类 聚合物会与脂质自组装。这些自组装的聚合物脂 系统将在10s纳米的订单上形成明确定义的光盘，从而产生脂质 膜模拟物适用于分析许多膜蛋白。高级 聚合物化学技术将使聚合物的长度，费用和 疏水性。通过GPC MALS分析的聚合物分析将提供有关该的详细信息 聚合物的性能，设施结构 - 聚合物之间的功能关系 他们的自组装结构。聚合物也将用自旋标记进行修饰 电子顺磁共振光谱。电子顺磁共振 光谱法将用于改性的聚合物，脂质和膜蛋白 具有适当的自旋标签，提供有关局部动态和接近的见解 自组装的聚合物脂质和聚合物 - 纤维 - 膜膜蛋白复合物。这些 洞察力可用于指导聚合物的设计，以实现强大的脂质膜模拟物。 本科生的培训和心理以及研究生助理将 成为拟议项目的核心特征。本科生将被充分整合 进入项目，包括聚合物分析，以及研究生，获得 材料科学与生物物理学界面的该领域的技能。