GE AKTAEXPLORER CHROMOTOGRAPHY SYSTEM

描述（由申请人提供）：在全球范围内，对抗菌药物的耐药性正在上升，迫切需要新的抗菌药物来对抗严重的人类病原体，如疟疾和耐药细菌。药物开发的转化工作依赖于小分子化合物文库的高通量筛选，以确定抑制微生物细胞功能或毒素作用的新分子。这些“命中”，通过筛选确定，是先导化合物，可能是新的抗菌化合物开发的骨干。这种筛选工作的一个关键组成部分是要筛选的大量微生物酶目标的纯化。我们的实验室已经成功地实施了针对两个这样的靶点的筛选，并正在开发针对其他几个微生物靶点的检测方法。为此，要求支持GE AktaExplorer液相色谱系统。该系统具有多种自动化功能（如pH值和色谱柱检测），专为生物分子纯化的快速开发和优化而设计。其他组件包括分数收集（基于内置的UV， pH，时间或电导率监测），自动采样和简单的操作软件，可为多个用户提供显著的灵活性。该系统的获得将极大地帮助高通量筛选工作，目前受到当前色谱设备的限制。由这一共享工具支持的NIH资助的研究项目包括：(1)疟疾和其他人类寄生虫病的药物开发（贝弗利、奥多姆、西布利和托利亚）；(2)细菌抗毒素药物开发（Haslam）；(3)抗病毒药物开发（法语）；和受体配体相互作用（Bu, Schwartz）。该项目汇集了几位美国国立卫生研究院资助的研究人员，他们对高端蛋白质纯化系统有着类似的需求。所有的研究人员都在儿科和分子微生物学部门，包括两个部门的各自主席。所有的实验室都在麦克唐纳儿科研究大楼内，AKTA系统将被安置在那里。作为首席研究员，奥多姆博士将主要负责监督设备。一个由主要用户组成的咨询委员会已经成立，负责监督设备的使用和维修。有强有力的机构和部门承诺住房和维护AKTA系统。为此，儿科部门已经承诺为维护和服务合同提供资金，确保Akta系统在未来至少10到15年的时间里以最佳状态运行，持续支持nih资助的华盛顿大学研究。

DESCRIPTION (provided by applicant): Globally, resistance to antimicrobial agents is on the rise, and new antimicrobial agents are urgently needed to counter severe human pathogens such as malaria and resistant bacteria. Translational efforts towards drug development depend on high-throughput screening of small molecule compound libraries, in order to identify new molecules that inhibit microbial cellular function or toxin action. These "hits," identified by screening, are lead compounds that may be the backbone of new antimicrobial compound development. A key component of such screening efforts is purification of large amounts of the microbial enzymatic target that is to be screened. Our laboratories have already successfully implemented screens against two such targets and are developing assays for several additional microbial targets. To this end, support is requested for a GE AktaExplorer liquid chromatography system. With multiple automated features (such as pH and column scouting), this system is designed for rapid development and optimization of biomolecular purification. Additional components include fraction collection (on the basis of built-in UV, pH, time, or conductivity monitoring), autosampling, and straightforward operational software that would provide significant flexibility for multiple users. Acquisition of this system would significantly aid high- throughput screening efforts that are currently limited by current chromatographic equipment. NIH funded research projects to be supported by this shared instrument include the following: (1) drug development for malaria and other human parasitic diseases (Beverley, Odom, Sibley, and Tolia); (2) bacterial anti-toxin drug development (Haslam); (3) anti-viral drug development (French); and receptor ligand interactions (Bu, Schwartz). The project brings together several NIH-funded investigators with similar needs for a high-end protein purification system. All of the investigators are in the Departments of Pediatrics and Molecular Microbiology, including respective Chairs of both Departments. All laboratories are within the McDonnell Pediatric Research Building, where the AKTA system will be housed. As principal investigator, Dr. Odom will be principally responsible for overseeing the equipment. An Advisory Committee comprised of major users has been convened to oversee usage and maintenance of the apparatus. There is strong institutional and departmental commitment to housing and maintaining the AKTA system. To that end, the Department of Pediatrics has committed to providing funds for maintenance and service contracts, ensuring the Akta system will function in peak form for at least the next 10 to 15 years in ongoing support of NIH-funded research at Washington University. PUBLIC HEALTH RELEVANCE: A collaborative group of seven NIH-supported investigators from the Departments of Pediatrics and Molecular Microbiology at Washington University School of Medicine request funding for the purchase of an ATKA Explorer 100 Air liquid chromatography system. Each of the investigators requires highly purified proteins to answer basic questions about human disease or to perform high-throughput screening (HTS) of small molecule inhibitors that hold potential as novel therapies against parasitic, viral, and toxin-mediated diseases. As such, the AKTA Explorer will directly facilitate the research undertaken by each investigator and contribute directly to human health.