CORE--SCIENCE FACILITY

科学核心的存在将为该计划项目赠款和神经病理学核心内的各种项目提供试剂和服务。在许多情况下，多个项目对特定试剂和服务的需求是共同的，因此，通过有重点和有技能的工作人员集中提供这些试剂和服务将是最有效的运作方法。将提供的试剂和服务包括：为临床试验招募的散发性CJD患者的DNA测序，以确认他们的PrP基因没有致病突变；提纯和分离喹卡林的立体异构体；用于表征新化合物的分析化学；从组合合成和合理的药物设计研究中初步筛选新化合物的大规模细胞分析； 奎纳克林在人和小鼠体内的代谢和药代动力学研究 药物化学项目中其他先导化合物代谢和药代动力学的测定；放射性标记药物类似物的合成和药物在脑组织中的生物利用度的测定；表面等离子共振(BIACORE)相互作用分析；用于检测潜在药物的纯化感染普恩病毒；用于携带显性负突变或P101 L突变的PrP的13C和15N标记重组蛋白的核磁共振研究；用于组织学和细胞研究的抗体。这一核心将由两名资深科学家指导，他们在Pron研究、分析化学、蛋白质化学、分子生物学、免疫学、抗体生产、重组蛋白质技术和自动化分析开发方面都有丰富的经验。他们将监督一组科学研究助理，这些助理将履行上述职能。

The Scientific Core will exist to provide reagents and services to the various projects within this program project grant and the Neuropathology Core. In many cases the need for specific reagents and services will be common to multiple projects, thus providing them centrally through a focused and skilled staff will be the most efficient method of operation. The reagents and services to be provided will include the following: DNA sequencing of sporadic CJD patients recruited for the clinical trial to confirm that they have no pathogenic mutations in their PrP genes; purification and isolation of the stereoisomers of quinacrine; analytical chemistry for characterization of new chemical compounds; large scale cell-based assays for initial screening of new compounds from combinatorial synthesis and from rational drug design studies; determination of the metabolism and pharmacokinetics of quinacrine in both humans and mice; determination of the metabolism and pharmacokinetics of other lead compounds that emerge from either of the medicinal chemistry projects; synthesis of radiolabeled drug analogs and the determination of the bioavailability of drugs in brain tissue; interaction analysis by surface plasmon resonance (Biacore); purified infectious prions for assaying potential drugs; 13C and 15N-labeled recombinant proteins for NMR studies of PrP carrying a dominant-negative mutation or the P101 L mutation; antibodies for histology and cell-based studies. This core will be directed by two senior scientists who between them have extensive experience of prion research, analytical chemistry, protein chemistry, molecular biology, immunology, antibody production, recombinant protein technology, and development of automated assays. They will supervise a group of scientific research associates who will carry out the functions listed above.