Instrumentation for Genetic and Chemical Screening

描述(由申请人提供)：本提案的目标是在斯坦福大学创建一个新的高通量筛查(HTS)设施。遗传学和化学合成的最新进展促进了生物医学研究的新策略，高通量液体处理和数据采集仪器将使斯坦福大学的教职员工和学生能够利用这些新的科学方法。例如，整个基因组的测序和选择性改变基因表达的技术的发展，现在基本上可以对任何基因产品进行快速功能评估。筛选天然产品和合成化学品中的生物活性化合物也正在成为破译生物过程的一种强有力的补充方法。 拟建的Biomek FX机器人液体处理工作站和EnVision多标签微孔板读取器将构成该设施的主要仪器系统，使用该设备，斯坦福大学的研究人员将能够对涉及遗传和/或化学扰动的生物系统进行系统和全面的筛查。可能的方法包括：(1)用于体内或体外蛋白质表达的cDNA文库；(2)用于靶向下调蛋白质表达的siRNA文库；以及(3)用于识别特定生物过程的小分子调节剂的化学文库。拟议中的HTS设施将由分子药理学系开发和管理，该提案中特别概述的研究项目涉及其教职员工关于心肌肥大、神经元功能、药物输送策略、胚胎信号通路和肿瘤发生机制的研究。然而，应该强调的是，这些调查只是高温超导设施将支持的各种研究活动的代表。整个斯坦福大学研究界及其邻近机构都可以使用，拟议的仪器将通过促进生物医学科学中全基因组方法的使用和化学生物学研究的进步，广泛地促进我们对人类健康和疾病的分子和细胞理解。

DESCRIPTION (provided by applicant): The objective of this proposal is to create a new high-throughput screening (HTS) facility at Stanford University. Recent advances in genetics and chemical synthesis have fostered novel strategies for biomedical research, and high-throughput liquid-handling and data acquisition instrumentation will enable Stanford faculty and students to exploit these new scientific approaches. For example, the sequencing of entire genomes and the development of techniques to selectively alter gene expression now permit the rapid functional evaluation of essentially any gene product. The screening of natural products and synthetic chemicals for biologically active compounds is also emerging as a powerful complementary approach for deciphering biological processes. The proposed Biomek FX robotic liquid-handling workstation and EnVision multi-label microplate reader will constitute the primary instrumentation systems of this facility, and with this equipment, Stanford researchers will be able to conduct systematic and comprehensive screens of biological systems involving genetic and/or chemical perturbations. Possible approaches include the use of: (1) cDNA libraries for in vivo or in vitro protein expression; (2) siRNA libraries for targeted 'knock-downs' of protein expression; and (3) chemical libraries for the identification of small molecule modulators of specific biological processes. The proposed HTS facility will be developed and managed by the Department of Molecular Pharmacology, and the research projects specifically outlined in this proposal involve studies by its faculty members that pertain to cardiac hypertrophy, neuronal function, drug delivery strategies, embryonic signaling pathways, and mechanisms of oncogenesis. It should be emphasized, however, that these investigations are merely representative of the diverse research activities that the HTS facility will support. Available to the entire Stanford research community and its neighboring institutions, the proposed instrumentation will broadly advance our molecular and cellular understanding of human health and disease by promoting the use of genome-wide approaches in the biomedical sciences and the advancement of chemical biology research.