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

我们需要一个机器人和仪器仪表的集成平台来更新加州大学圣克鲁斯化工厂 筛选中心（CSC），一个共享的研究设施，支持美国国立卫生研究院资助的生物医学研究在UC 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，包括生物钟的调查，宿主-病原体相互作用，细胞周期，RNA 拼接、非洲河盲症等热带疾病，以及制定自然 产品发现CSC的活动已产生超过50种同行评审出版物，其中大部分 是由来自不同部门和专业的教师共同撰写的，许多赠款已获得资助 根据CSC获得的初步数据。HTS是发现生物活性小分子的核心， 作为药物先导或生物工具化合物。由于液体处理机器人和化学图书馆的成本 在过去的十年中，HTS已经成为学术研究的强大发现工具， 实验室虽然CSC是UCSC的一个重要的共享研究设施，拥有强大的行政支持， 它目前的配置存在瓶颈，限制了它对NIH资助的关键项目的潜在影响。经过13 经过多年的持续运行，CSC的堆芯液体处理仪器变得越来越不可靠， 需要更换。所提出的显微镜提供了更好的图像质量，更快的采集时间， 和更有效的图像分析软件，以不断增长的用户群在UCSC谁依赖于基于图像的 筛选他们的研究。随着对小分子方法的兴趣在NIH资助的 在UCSC的生物医学界，我们必须提高我们筛选的效率和准确性， 仪器仪表现代化我们的自动化液体处理系统不仅可以让CSC继续 操作在目前的吞吐量，但将改变设施，使筛选在1536孔板， 从而能够筛选100，000个小分子的更大的替换文库，UCSC已经 作为对该提案的机构承诺的一部分，提出购买。事实上，机构 承诺是非常强大的，支持两个全职员工至少5年后安装，加上一个 应急计划，以确保设施在预算短缺的情况下不间断地运作。 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，其中许多系统具有 直接治疗应用，拟议的升级将使这一重要设施继续催化 在未来的几年里，NIH资助的科学进步。

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.