A UK National Protein Production Facility for Biomedically Driven Structural Proteomics

人类基因组计划在大约10-15年的时间里，在DNA测序以及大型生物数据库的操作和管理方面取得了许多数量级的进展。由此产生的人类基因组序列被誉为划时代的成就，为人类医疗保健的进步带来了在很大程度上未知的机会。在实用层面上，人们普遍认为，只有当基因组信息得到我们对蛋白质功能的理解的进步的补充时，这种进步才能发生。蛋白质的完整功能描述需要了解其三维结构，通常是作为大型多分子组装的一部分，但基因组序列的确定速度远远超过结构确定的速度。牛津蛋白质生产设施-英国(OPPF-UK)的目标是通过开发高通量工具来促进这一过程，以过度表达和结构解决人类蛋白质和来自人类病原体的蛋白质。在试验阶段，该项目组装了一条用于蛋白质生产的管道，在几个领域涉及复杂的数据管理和机器人技术。这些技术对来自细菌病原体的蛋白质非常有效，目前的挑战是改进这些技术，以提高它们对人类和病毒蛋白质的有效性。目标选择将涉及选择比应用标准实验室方法更有效地提出具有生物医学重要性的问题的领域。其目的是与包括分子、细胞和临床研究在内的成熟的跨学科研究网络相结合。OPPF-UK将成为一个多学科研究中心的一部分，该中心将建在钻石光源附近，英国S新的同步加速器研究设施。OPPF-UK将成为汇集生物、物理和材料科学的独特环境的一部分。

The human genome project, over some 10-15 years, has advanced by many orders of magnitude DNA sequencing and the manipulation and management of large biological data bases. The resulting sequence of the human genome has been hailed as an epoch making achievement ushering in as yet largely uncharted opportunities for advances in human healthcare. At a pragmatic level it is generally accepted that such advances can only occur when the genomic information is complemented by advances in our understanding of protein function. A full functional description of a protein requires knowledge of its 3D structure, often as part of a large multi-molecular assembly, but the rate of determination of genomic sequences has far outstripped that of structure determination. The aim of the Oxford Protein Production Facility - UK (OPPF-UK) is to facilitate this process by developing high throughput tools for the over-expression and structure solution of human proteins and proteins from human pathogens. In the pilot phase the project has assembled a pipeline for protein production involving sophisticated data management and robotic technologies in several areas. These technologies are highly effective for proteins from bacterial pathogens and the challenge now is to refine these technologies to increase their effectiveness for human and viral proteins. Target selection will involve choosing areas where problems of biomedical importance can be advanced more effectively than by the application of standard laboratory methods. The intention is to mesh with well established networks of interdisciplinary research covering molecular, cellular and clinical studies. The OPPF-UK will form part of a multi-disciplinary Research Centre to be built adjacent to the Diamond Light Source, the UK?s new synchrotron research facility. The OPPF-UK will part of a unique environment bringing together biological, physical and material sciences.