GE AKTAEXPLORER CHROMOTOGRAPHY SYSTEM

GE AKTAEXPLORER 色谱系统

• 批准号: 7794250
• 负责人: Audrey Ragan Odom John
• 金额: $ 12.18万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-08 至 2011-04-07
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7794250
• 关键词: Advisory Committees; Air; Anti-Bacterial Agents; Antimicrobial Resistance; Biological Assay; Cell physiology; Collection; Commit; Computer software; Contract Services; Development; Disease; Ensure; Equipment; Funding; Health; Housing; Human; Laboratories; Lead; Libraries; Ligands; Liquid Chromatography; Maintenance; Malaria; Mediating; Microbiology; Molecular; Monitor; Parasitic Diseases; Pediatric Research; Principal Investigator; Proteins; Research; Research Personnel; Research Project Grants; Screening procedure; System; Time; Toxin; United States National Institutes of Health; Universities; Vertebral column; Viral; Washington; antimicrobial; antimicrobial drug; bacterial resistance; base; design; drug development; flexibility; high throughput screening; human disease; inhibitor/antagonist; instrument; medical schools; microbial; novel; pathogen; pediatric department; protein purification; public health relevance; receptor; small molecule

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.

描述（由申请人提供）：在全球范围内，对抗菌剂的耐药性正在上升，迫切需要新的抗菌剂来对抗严重的人类病原体，如疟疾和耐药细菌。药物开发的转化努力取决于小分子化合物文库的高通量筛选，以鉴定抑制微生物细胞功能或毒素作用的新分子。通过筛选鉴定的这些“命中物”是先导化合物，可能是新抗微生物化合物开发的支柱。这种筛选工作的一个关键组成部分是纯化大量待筛选的微生物酶靶标。我们的实验室已经成功地针对两个这样的目标进行了筛选，并正在开发针对其他几个微生物目标的检测方法。为此，需要支持GE AktaExplorer液相色谱系统。该系统具有多种自动化功能（如pH和柱搜索），专为快速开发和优化生物分子纯化而设计。其他组件包括馏分收集（基于内置的UV、pH值、时间或电导率监测）、自动采样和简单的操作软件，可为多个用户提供极大的灵活性。该系统的获得将大大有助于目前受当前色谱设备限制的高通量筛选工作。该共享工具支持的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（Beverley，Odom，Sibley和Tolia）;（2）细菌抗毒素药物开发（Haslam）;（3）抗病毒药物开发（法国）;和受体配体相互作用（Bu，Schwartz）。该项目汇集了几个NIH资助的研究人员，他们对高端蛋白质纯化系统有类似的需求。所有研究者都在儿科和分子微生物学部门，包括两个部门的各自主席。所有实验室都在McDonnell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召开会议，以监督仪器的使用和维修。有强有力的机构和部门的承诺，住房和维护AKTA系统。为此，儿科系已承诺为维护和服务合同提供资金，确保Akta系统至少在未来10至15年内以峰值形式运行，以持续支持华盛顿大学NIH资助的研究。 公共卫生相关性：来自华盛顿大学医学院儿科和分子微生物学系的七名NIH支持的研究人员组成的合作小组要求资助购买ATKA Explorer 100 Air液相色谱系统。每个研究人员都需要高度纯化的蛋白质来回答有关人类疾病的基本问题，或对小分子抑制剂进行高通量筛选（HTS），这些抑制剂有可能成为对抗寄生虫，病毒和毒素介导的疾病的新型疗法。因此，AKTA Explorer将直接促进每位研究人员进行的研究，并直接为人类健康做出贡献。