Acquisition of a High-throughput Confocal Imaging System

描述(由申请人提供)：几乎每个生物过程的核心都是潜在的细胞生物学，它使科学家能够“看到”细胞内发生的事情。因此，动态高分辨率成像已成为几乎所有生物实验室的支柱。虽然这项技术继续以快速的速度发展，但大部分成像仍然是低吞吐量的，在任何给定的时间只能分析一个样本。随着大规模基因组学、蛋白质组学和功能基因组学方法的出现成为新发现的主要途径，我们也必须有能力用高通量细胞学来补充这些研究。这项提议是为了获得高通量的共焦成像系统。拟议的仪器包括一个高通量显微镜系统、用于活体哺乳动物细胞工作的环境室、平板搬运机器人和数据服务器。该系统专门设计用于对多孔板格式(6-1536口井)的样品进行高含量成像。这种仪器将允许我们的用户处理一系列广泛的生物医学问题，这些问题可以通过高通量分析荧光标记的样本来解决。对细胞在有丝分裂过程中进行高分辨率成像的能力将使用户能够阐明细胞周期进展的分子机制，并潜在地识别化疗开发的新靶点。对微生物细胞分裂和分化以及生物膜形成进行高通量遗传筛选的能力将使用户能够深入了解控制这些过程的机制，并可能导致发现抗生素开发的新途径。最后，神经药理学信号在大脑功能的各个方面都是至关重要的。在高通量细胞学分析中进行药理筛选的能力将是对他们目前阐明信号转导途径的方法的重大改进。总体而言，拟议的仪器将对我校生命科学研究人员的研究方法和进展产生重大影响。

DESCRIPTION (provided by applicant): At the heart of nearly every biological process is the underlying cell biology that allows scientists to "see" what is happening within a cell. Dynamic high-resolution imaging has therefore become a mainstay in nearly any biological laboratory. While the technology has continued to evolve at a rapid pace, much of the imaging remains low-throughput where only a single sample can be analyzed at any given time. With the advent of large-scale genomics, proteomics, and functional genomics approaches being major routes to new discoveries, it is imperative that we also have the ability to complement those studies with high- throughput cytology. This proposal is to acquire a high-throughput confocal imaging system. The proposed instrumentation comprises a high-throughput microscope system, environmental chamber for live mammalian cell work, plate handling robotics and data servers. The system is specifically designed to perform high-content imaging of samples in a multi-well plate format (6-1536 wells). This instrumentation will allow our users to approach a wide array of biomedical questions that can be pursued through high- throughput analysis of fluorescently labeled samples. The ability to perform high-resolution imaging of cells progressing through mitosis will allow users to elucidate molecular mechanisms of cell cycle progression and the potential identification of new targets for chemotherapeutic development. The ability to perform high-throughput genetic screens of microbial cell division and differentiation as well as biofilm formation will allow users to gain insight into the mechanisms controlling these processes and may lead to the discovery of new pathways for antibiotic development. Finally neuropharmacological signaling is crucial in all aspects of brain function. The ability to perform pharmacological screens in high-throughput cytological assays would be a major enhancement over their current approaches of elucidating the signal transduction pathways. Overall the proposed instrumentation would have a significant impact on the research approaches and progress made by life sciences researchers at our university.