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

项目总结 此应用程序正在申请资金，以购买定制和集成的多角度光散射 (MALS)为基础的多探测系统。无缝集成的仪器设备结合了 MALS(静态光散射)，用于使用a)DLS(动态光)精确测定分子质量 散射)以获得分子大小和形状的完整图像b)SEC(大小排除层析； SEC-MALS)用于异相和多价络合物的分馏能力和表征， 和c)Cg(组成梯度；Cg-MALS)，用于停止流动电位和测定动力学和 复杂分子组装中的平衡离解常数(Pm到Mm)。 该仪器是为贝勒学院教职员工的紧急研究需求而定制的 医学部，致力于复杂的高分子量(MW)组件(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 抗体和淀粉样聚集体)和具有挑战性的系统(例如，固有的无序蛋白、PTM- 结合蛋白和药物结合或结合蛋白靶标)。有代表性的13大 用户和3个次要用户。不同蛋白质靶标的大分子表征在 了解蛋白质的细胞功能和功能障碍会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)。 该地区有三个已知的私人证券交易委员会工具，但没有共享设备。 也没有已知的CG-MAL可用，这是用户要表征的关键技术 复杂分子物种的分子相互作用。此外，大量的预期使用量 (包括高通量常规筛选)，以及大多数样本的敏感性迫使用户 请求此共享检测。该设备将成为生物分子表征核心的一部分 这将服务于BCM调查人员以及(TMC)德克萨斯医疗中心(例如赖斯)的研究人员 大学，MD安德森癌症中心)，德克萨斯州和其他地方。此外，MALS仪器将 成为BCM和TMC机构全球战略计划中的重要技术资源，以实现精确度 医学和翻译研究。

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.