Upgrade of core imaging instrumentation and robotics for the UCSC Chemical Screening Center

UCSC 化学筛查中心核心成像仪器和机器人升级

• 批准号: 10177241
• 负责人: Robert SCOTT LOKEY
• 金额: $ 193.18万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2022-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10177241
• 关键词: Address; African; Biological; Biomedical Research; Cell Cycle; Chemicals; Communities; Computer software; Data; Development; Employee; Ensure; Event; Faculty; Funding; Grant; Image; Image Analysis; Investigation; Laboratory Research; Libraries; Liquid substance; Methodology; Microscope; Modernization; Natural Products; Ocular Onchocerciasis; Peer Review; Pharmaceutical Preparations; Publications; RNA Splicing; Research; Robotics; Scientific Advances and Accomplishments; System; Therapeutic; Time; Tropical Disease; United States National Institutes of Health; Update; base; biological systems; circadian pacemaker; cost; improved; instrument; instrumentation; interest; medical specialties; operation; pathogen; research facility; screening; small molecule; small molecule libraries; tool

We request an integrated platform of robotics and instrumentation to update the UC Santa Cruz Chemical Screening Center (CSC), a shared research facility that has supported NIH-funded biomedical research at UC Santa Cruz since its inception in 2007. Research conducted at the CSC addresses a range of biomedical questions, including investigations of the circadian clock, host-pathogen interactions, the cell cycle, RNA splicing, tropical diseases such as African River Blindness, and development of methodologies for natural products discovery. Activity in the CSC has resulted in well over 50 peer-reviewed publications, most of which were jointly authored by faculty from different departments and specialties, and many grants have been funded based on preliminary data acquired at the CSC. HTS is central to the discovery of bioactive small molecules, either as drug leads or biological tool compounds. As the cost of liquid handling robotics and chemical libraries has declined during the past decade, HTS has become a powerful discovery tool for the academic research laboratory. While the CSC is an important shared research facility at UCSC with strong administrative support, bottlenecks exist in its current configuration that limit its potential impact on key NIH-funded projects. After 13 years of constant operation, the core liquid handling instruments in the CSC are becoming unreliable and are in need of replacement. The proposed microscope provides much better image quality, faster acquisition times, and more efficient image analysis software to the growing user base at UCSC who depend on image-based screening for their research. As interest in small molecule approaches has grown among the NIH-funded biomedical community at UCSC, we must improve the efficiency, and accuracy of our screening instrumentation. Modernizing our automated liquid handling system will not only allow the CSC to continue operations at the current throughput, but will transform the facility by enabling screening in 1536-well plates, thereby enabling the screening of a larger replacement library of 100,000 small molecules, which UCSC has offered to purchase as part of the Institutional Commitment to this proposal. Indeed, the Institutional Commitment is very strong, supporting two full-time employees for at least 5 years following installation, plus a contingency plan to ensure uninterrupted operation of the facility in the unlikely event of a budgetary shortfall. In short, the UCSC-CSC has facilitated exciting discoveries in a wide array of biological systems, many with direct therapeutic applications, and the proposed upgrade will allow this important facility to continue catalyzing NIH-funded scientific advances for years to come.

我们需要一个机器人和仪器的集成平台来更新加州大学圣克鲁斯化学公司 筛选中心(CSC)，这是一个共享的研究设施，支持加州大学NIH资助的生物医学研究 圣克鲁斯自2007年成立以来。在CSC进行的研究涉及一系列生物医学 问题，包括生物钟、宿主与病原体的相互作用、细胞周期、RNA 剪接，热带疾病，如非洲河盲，以及开发自然 产品发现。公务员制度委员会的活动产生了50多份同行评审的出版物，其中大多数 是由来自不同系和专业的教师共同撰写的，许多助学金已经得到了资助 基于在CSC获得的初步数据。高温超导是发现生物活性小分子的核心， 无论是作为药物先导化合物还是生物工具化合物。因为液体搬运机器人和化学图书馆的成本 在过去的十年中有所下降，HTS已经成为学术研究的强大发现工具 实验室。虽然CSC是加州大学洛杉矶分校一个重要的共享研究机构，拥有强大的行政支持， 其目前的配置存在瓶颈，限制了其对NIH资助的关键项目的潜在影响。13年后 经过多年的不断运行，CSC的岩心液体装卸仪表变得不可靠，而且 需要换新的。所提出的显微镜提供更好的图像质量，更快的采集时间， 为加州大学洛杉矶分校日益增长的依赖基于图像的用户群提供更高效的图像分析软件 为他们的研究进行筛选。随着对小分子的兴趣在NIH资助的 在加州大学圣迭戈分校的生物医学界，我们必须提高筛查的效率和准确性 仪器仪表。我们的自动化液体处理系统的现代化不仅将使CSC继续 在目前的生产能力下运行，但将通过在1536孔板上进行筛选来改变设施， 从而能够筛选出由100,000个小分子组成的更大的替换库，UCSC拥有 提出购买，作为机构对这一提议的承诺的一部分。事实上，机构 承诺非常强烈，在安装后支持两名全职员工至少5年，外加 应急计划，以确保设施在不太可能出现预算缺口的情况下不间断运行。 简而言之，UCSC-CSC在广泛的生物系统中促进了令人兴奋的发现，其中许多 直接治疗应用，拟议的升级将使这一重要设施继续催化 美国国立卫生研究院为未来几年的科学进步提供资金。