Antibody Research Technology Center

描述（由申请人提供）：抗体技术资源中心（ATRC）的目标是开发高质量重组抗体（rAbs）的技术，以产生高价值的蛋白质靶点，这些靶点已被证明是难以产生Ab的。抗体是确定蛋白质在正常和病理生理条件下如何发挥作用的基本试剂，但大多数蛋白质组无法获得抗体，即使可用，抗体的质量也不稳定。广泛可用、可再生、经过验证和标准化的rAbs集合的产生将显著加快蛋白质功能的研究。我们专注于生成分泌的细胞外和膜蛋白以及蛋白质翻译后修饰的rAbs，因为：1)它们占所有蛋白质的20-40%，2)它们已被证明具有挑战性，无论是表达，纯化和/或成功用于Ab生成。加州大学旧金山分校（UCSF）的ATRC有三个技术研究与开发（TR&D）项目，将开发新的高通量抗原和抗体生成技术来生成rAbs。项目1)利用酵母展示的抗原、细胞系和噬菌体抗体文库，开发针对分泌的细胞外、单代和多代膜蛋白生成rAbs的技术，项目负责人：James D. Marks；项目2)开发技术，生成调节蛋白酶功能的功能性rAbs，项目负责人：Charles Craik；项目3)开发技术，生成翻译后修饰及其构象的rAbs，项目负责人：James Wells。推动UCSF和其他地方的生物医学项目将为目标选择提供信息，提供一些抗原，并使用和验证由中心生成的rAbs进行结构和功能分析。这些正在进行的美国国立卫生研究院资助的项目将受益于随时获得高质量的抗体。对这些技术的培训将通过举办年度研讨会、讲习班、网络研讨会以及对访问调查人员进行技术使用方面的现场培训来完成。试剂的传播将通过公布方法、分发含有抗体基因的质粒、抗体载体、表达抗体的细胞系和抗体试剂来完成。

DESCRIPTION (provided by applicant): The goal of the Antibody Technology Resource Center (ATRC) is to develop technologies to generate high quality recombinant antibodies (rAbs) to high-value protein targets that have proven difficult for Ab generation. Abs are essential reagents for determining how proteins function under normal and pathophysiological conditions yet are not available for much of the proteome and when available are of -variable quality. The generation of widely available, renewable, validated and standardized sets of rAbs will significantly accelerate studies of protein function. We are focusing on generating rAbs to secreted extracellular and membrane proteins and protein post-translational modifications since: 1) they comprise 20-40% of all proteins and 2) they have proven challenging to either express, purify and/or successfully use for Ab generation. The ATRC at the University of California, San Francisco (UCSF) has three Technology Research and Development (TR&D) projects that will develop novel high throughput antigen and antibody generation technology to generate rAbs. Project 1) Develop technology to generate rAbs to secreted extracellular, single pass and multipass membrane proteins using yeast displayed antigens, cell lines and phage antibody libraries, Project Leader: James D. Marks; Project 2) Develop technology to generate functional rAbs to proteases that modulate protease function, Project Leader: Charles Craik; and Project 3) Develop technology to generate rAbs to post-translational modifications and their conformers, Project Leader: James Wells. Driving biomedical projects at UCSF and elsewhere will inform target selection, provide some of the antigens and use and validate rAbs generated by the Center for structural and functional assays. These ongoing NIH-funded projects will benefit from ready access to high quality rAbs. Training in the technologies will be accomplished by hosting an annual symposium, workshops, webinars, and by onsite training of visiting investigators in the use of technology. Dissemination of reagents will be accomplished by publication of methods, and by distribution of plasmids containing antibody genes, antibody vectors, antibody expressing cell lines and antibody reagents.