Customized and Integrated Multi-Angle Light Scattering (MALS)-based Multidetection System

基于定制和集成多角度光散射 (MALS) 的多重检测系统

• 批准号: 10415734
• 负责人: Josephine Chu Ferreon
• 金额: $ 33.48万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-15 至 2023-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10415734
• 关键词: Amyloid; Binding; Cancer Center; Cell physiology; Complex; Custom; DNA; Disease; Dissociation; Equilibrium; Equipment; Faculty; Fractionation; Functional disorder; Funding; Institution; Kinetics; Life; Malignant Neoplasms; Medical center; Medicine; Membrane Proteins; Membrane Transport Proteins; Minor; Molecular; Molecular Sieve Chromatography; Molecular Weight; Neurodegenerative Disorders; Pharmaceutical Preparations; Privatization; Proteins; RNA; Research; Research Personnel; Resources; Rice; Sampling; Strategic Planning; System; Techniques; Texas; Therapeutic antibodies; Translational Research; Universities; Viral; Viral Proteins; base; college; detection platform; instrument; instrumentation; light scattering; molecular assembly/self assembly; molecular mass; molecular shape; molecular size; particle; precision medicine; routine screening

PROJECT SUMMARY This application is requesting funds to purchase a customized and integrated Multi-Angle Light Scattering (MALS)-based multi-detection system. The seamless integrated instrumentation combines the power of MALS (static light scattering) for accurate molecular mass determination with a) DLS (dynamic light scattering) for a complete picture of molecular sizes and shapes b) SEC (size exclusion chromatography; SEC-MALS) for fractionation capability and characterization of heterogeneous and multivalent complexes, and c) CG (composition gradient; CG-MALS) for stopped flow potential and determination of kinetic and equilibrium dissociation constants (pM to mM) in complex molecular assemblies. The instrumentation is customized to the emergent research needs of the faculty at Baylor College of Medicine, working on complex high molecular weight (MW) assemblies (e.g. multi-protein, multi- protein:DNA/RNA, membrane proteins and transporters, viral-like particles and viral proteins, therapeutic antibodies, and amyloid aggregates) and challenging systems (e.g. intrinsically disordered proteins, PTM- conjugated proteins and drug-bound or conjugated protein targets). There are representative 13 Major Users and 3 Minor Users. Macromolecular characterization of the various protein targets is essential in understanding the protein's cellular function and dysfunction leading to many life-threatening (e.g. infectious, cancer and neurodegenerative) diseases. There are three known private SEC-MALS instruments and no shared equipment in the region. There is also no known CG-MALS available, which is a critical technique for users to characterize molecular interactions of complex molecular species. Furthermore, the high volume of anticipated usage (including high throughput routine screening), and the sensitivity of most samples compel the users to request this shared instrumentation. The equipment will be part of a biomolecular characterization core that will serve BCM investigators, as well as researchers in the (TMC) Texas Medical Center (e.g. Rice University, MD Anderson Cancer Center), Texas and beyond. In addition, the MALS instrumentation will be an essential technical resource in the global strategic plans of BCM and TMC institutions for precision medicine and translational research.

项目概要 此应用程序正在请求资金购买定制的集成多角度光散射 (MALS)为基础的多重检测系统。无缝集成仪器结合了 MALS（静态光散射），用于通过 a) DLS（动态光散射）进行准确的分子质量测定 b) SEC（尺寸排阻色谱法；散射）以获得分子大小和形状的完整图像 SEC-MALS）用于异质和多价复合物的分馏能力和表征， c) CG（成分梯度；CG-MALS）用于停流电位和动力学和 复杂分子组装体中的平衡解离常数（pM 至 mM）。 该仪器是根据贝勒学院教师的紧急研究需求定制的 医学博士，致力于复杂的高分子量（MW）组装（例如多蛋白质、多 蛋白质：DNA/RNA、膜蛋白和转运蛋白、病毒样颗粒和病毒蛋白、治疗性 抗体和淀粉样蛋白聚集体）和具有挑战性的系统（例如本质上无序的蛋白质、PTM- 缀合蛋白质和药物结合或缀合蛋白质靶标）。有代表性的13个专业 用户和 3 个次要用户。各种蛋白质靶标的大分子表征对于 了解蛋白质的细胞功能和功能障碍导致许多危及生命的事件（例如 传染病、癌症和神经退行性疾病）。 该地区有三台已知的私有 SEC-MALS 仪器，没有共享设备。 也没有已知的 CG-MALS 可用，这是用户表征的关键技术 复杂分子种类的分子相互作用。此外，预期使用量很大 （包括高通量常规筛选），大多数样品的敏感性迫使用户 请求这个共享仪器。该设备将成为生物分子表征核心的一部分 将为 BCM 研究人员以及 (TMC) 德克萨斯医学中心的研究人员（例如 Rice 大学、MD 安德森癌症中心）、德克萨斯州及其他地区。此外，MALS 仪器将 成为 BCM 和 TMC 机构精准全球战略计划中的重要技术资源 医学和转化研究。