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

描述(由申请人提供)：我们正在申请购买高通量自动化的资金，用于体外选择和鉴定重组抗体。抗体将展示在噬菌体或酵母上，并针对纯化的或展示在真核细胞上的抗原进行筛选。这些抗体将作为生物探针、生物标记物和潜在的治疗药物。加州大学旧金山分校或附近的校园目前还没有适用于这项技术的仪器。因此，这种高通量自动化的增加将在加州大学旧金山分校服务于一个独特的目的，同时支持至少五个由NIH资助的项目。新设备将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UC社区开放。SMDC已经制定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，因此能够最大限度地利用新的自动化进行技术开发。抗体是决定蛋白质在正常或病理生理条件下功能的基本试剂。抗体的用途包括对蛋白质进行量化，识别细胞和组织中表达的时空模式，以及识别相互作用的伙伴。这类研究需要具有高度特异性的抗体，这些抗体可用于免疫印迹、免疫沉淀、免疫组织化学(IHC)和活体成像等检测。超过一半的人类蛋白质组没有注释，这些蛋白质的功能抗体也不可靠。通过使用展示技术和抗体基因多样性文库，可以克服传统抗体生成的许多局限性。该仪器的购买得到了三个主要用户的广泛支持，这些用户拥有来自加州大学旧金山分校两个不同校区的三个系的良好研究计划。自动化将支持NIH资助的整个加州大学旧金山分校对这些用户和未来的未成年人用户的研究。

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.