Automated System for High-Throughput In Vitro Selection of Recombinant Antibodies

描述（由申请人提供）：我们正在申请资金购买高通量自动化，用于重组抗体的体外选择和表征。抗体将显示在噬菌体或酵母上，并选择对抗纯化或显示在真核细胞上的抗原。这些抗体将作为生物探针、生物标记物和潜在的治疗药物。目前，在加州大学旧金山分校或附近的校园里，还没有适合这项技术的仪器。因此，这种高通量自动化的增加将为UCSF提供独特的目的，同时支持至少五个nih资助的项目。新设备将被放置在加州大学旧金山分校的小分子发现中心（SMDC），并向整个加州大学社区开放。SMDC已经建立了维护该设备的空间、人员和充值政策。SMDC包括一个高通量筛选（HTS）小组，因此处于有利地位，可以最大限度地利用新的自动化技术开发。抗体是确定蛋白质在正常或病理生理条件下如何发挥作用的基本试剂。抗体的用途包括定量蛋白质，识别细胞和组织中的时间和空间表达模式，以及识别相互作用的伙伴。这类研究需要具有高特异性的抗体，这些抗体可以在Western blotting、免疫沉淀、免疫组织化学（IHC）和体内成像等检测中发挥作用。超过一半的人类蛋白质组没有被注释，这些蛋白质的功能性抗体也不可靠。传统抗体生成的许多局限性可以通过使用显示技术和抗体（Ab）基因多样性文库来克服。该仪器的购买得到了三个主要用户的广泛支持，这些用户来自UCSF两个不同校区的三个部门，拥有完善的研究项目。自动化将支持NIH资助的这些用户和未来在UCSF的次要用户的研究。

DESCRIPTION (provided by applicant): We are requesting funds to purchase high throughput automation for the in vitro selection and characterization of recombinant antibodies. The antibodies will be displayed on phage or yeast, and selected against antigens that are either purified or displayed on eukaryotic cells. These antibodies will serve as biological probes, biomarkers and potential therapeutics. There is currently no appropriate instrumentation for this technology at UCSF or nearby campuses. The addition of this high-throughput automation would therefore serve a unique purpose at UCSF, while supporting at least five NIH-funded projects. The new equipment would be placed in the Small Molecule Discovery Center (SMDC) at UCSF and be available to the entire UC community. The SMDC has already established the space, staff, and recharge policies to maintain this equipment. The SMDC includes a high-throughput screening (HTS) group and is therefore well-positioned to maximize the use of new automation for technology development. Antibodies are essential reagents for determining how proteins function under normal or pathophysiological conditions. Uses of antibodies include quantifying proteins, identifying the temporal and spatial pattern of expression in cells and tissue, and identifying interacting partners. Such studies require antibodies of high specificity that function in assays including Western blotting, immunoprecipitation, immunohistochemistry (IHC) and in vivo imaging. Over half the human proteome is not annotated and functional antibodies are not reliably available for these proteins. Many of the limitations of traditional antibody generation can be overcome by the use of display technologies and antibody (Ab) gene diversity libraries. The purchase of this instrument has broad support from three major users with well-established research programs from three departments at two different UCSF campuses. The automation would support the NIH funded research of these users and future minor users throughout UCSF.