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SIG Program: AKTAxpress FPLC System for Protein Purification

SIG 计划：用于蛋白质纯化的 AKTAxpress FPLC 系统

基本信息

批准号：
7794720
负责人：
FRANCES H ARNOLD
金额：
$ 17.58万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-05-06 至 2011-05-05
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): AKTAxpress FPLC System for Protein Purification 1) Project Summary/Abstract Protein purification capabilities underlie structural biology, protein design, and all aspects of protein science. High-throughput automated protein purification can greatly enhance research productivity when many samples must be handled and multi-step purification protocols optimized. Three leading protein research laboratories at Caltech (Arnold, Rees, Tirrell) are requesting support to purchase an AKTAxpress FPLC (Fast Protein Liquid Chromatography) system. This instrument is capable of performing fully- automated, multi-step purifications in an unattended fashion, resulting in highest possible purity and high yields for applications such as crystallography and biochemical protein characterization. The modular setup allows different purification protocols to be run simultaneously on different modules, enabling the three research groups to purify their proteins without interfering with each other. This instrument will remove a very significant bottleneck to our research efforts: protein purification. Time on current purification systems is fully booked, and requires significant researcher input that will be minimized with the AKTAxpress. The modular setup also allows expansion of capabilities when needed (with addition of new purification 'modules', for a total of up to 12). This instrument will support research into the structural basis of cytochrome P450 function and engineering new P450s for synthesis of human metabolites and drug lead diversification (Arnold), membrane protein crystallographic structure analysis (Rees), and engineering proteins through incorporation of nonnatural amino acids (Tirrell). Cytochrome P450 enzymes are key players in human drug metabolism, and understanding their function is critical to development of safe, effective therapeutics. These enzymes can be used to synthesize authentic metabolites for clinical testing (e.g. for toxicity or enhanced therapeutic function). Integral membrane proteins are targets of most popularly prescribed drugs, yet their structural analysis is still in its infancy. Protein engineering via incorporation of nonnatural amino acids offers exciting new opportunities for protein-based therapeutics and diagnostics as well as new research tools. PUBLIC HEALTH RELEVANCE: The research supported by this instrumentation grant will lead to a better understanding of drug metabolism, drug-drug interactions, and mechanisms of drug action. Protein purification is a fundamental tool in structural biology, protein design, and all aspects of protein science. Protein purification is currently a bottleneck for all three groups requesting this instrumentation, and their research productivity will be significantly enhanced by the requested protein purification system.

描述（由申请人提供）：AKTAxpress FPLC蛋白质纯化系统1）项目概述/摘要蛋白质纯化能力是结构生物学、蛋白质设计和蛋白质科学各个方面的基础。高通量自动化蛋白质纯化可以大大提高研究生产力，当许多样品必须处理和多步纯化方案优化。加州理工学院的三个领先的蛋白质研究实验室（Arnold、Rees和Tirrell）正在寻求支持，以购买AKTAxpress FPLC（快速蛋白质液相色谱）系统。该仪器能够以无人值守的方式进行全自动、多步纯化，从而为晶体学和生物化学蛋白质表征等应用提供尽可能高的纯度和高产率。模块化设置允许在不同模块上同时运行不同的纯化方案，使三个研究小组能够在不相互干扰的情况下纯化他们的蛋白质。该仪器将消除我们研究工作的一个非常重要的瓶颈：蛋白质纯化。目前的净化系统的时间已经排满，需要大量的研究人员投入，而AKTAxpress将最大限度地减少这些投入。模块化设置还允许在需要时扩展功能（添加新的纯化“模块”，总共多达12个）。该仪器将支持对细胞色素P450功能的结构基础的研究，并设计新的P450以合成人类代谢物和药物铅多样化（Arnold）、膜蛋白晶体结构分析（Rees）以及通过掺入非天然氨基酸来工程蛋白质（Tirrell）。细胞色素P450酶是人类药物代谢的关键参与者，了解它们的功能对于开发安全，有效的治疗方法至关重要。这些酶可用于合成用于临床测试的真实代谢物（例如用于毒性或增强的治疗功能）。整合膜蛋白是最常用的处方药物的靶点，但它们的结构分析仍处于起步阶段。通过掺入非天然氨基酸的蛋白质工程为基于蛋白质的治疗和诊断以及新的研究工具提供了令人兴奋的新机会。公共卫生相关性：这项仪器补助金支持的研究将导致更好地了解药物代谢，药物相互作用和药物作用机制。蛋白质纯化是结构生物学、蛋白质设计和蛋白质科学各个方面的基本工具。蛋白质纯化目前是要求该仪器的所有三个组的瓶颈，并且所要求的蛋白质纯化系统将显著提高他们的研究生产率。