CORE--SCIENCE FACILITY

科学核心将存在，以提供试剂和服务的各种项目在这个程序项目赠款和神经病理学核心。在许多情况下，对特定试剂和服务的需求将是多个项目共同的，因此，通过重点突出和熟练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。提供的试剂和服务将包括：对临床试验招募的散发性克雅二氏症患者进行DNA测序，以确认他们的PrP基因没有致病突变;纯化和分离奎纳克林的立体异构体;分析化学，以确定新化合物的特征;用于从组合合成和合理药物设计研究中初步筛选新化合物的大规模基于细胞的测定; 测定奎纳克林在人类和小鼠中的代谢和药代动力学; 确定药物化学项目中出现的其他先导化合物的代谢和药代动力学;合成放射性标记的药物类似物并确定药物在脑组织中的生物利用度;通过表面等离子体共振（Biacore）进行相互作用分析;用于测定潜在药物的纯化感染性朊病毒; 13 C和15 N标记的重组蛋白用于携带显性负突变或P101 L突变的PrP的NMR研究;用于组织学和基于细胞的研究的抗体。该核心将由两名资深科学家指导，他们在朊病毒研究、分析化学、蛋白质化学、分子生物学、免疫学、抗体生产、重组蛋白技术和自动化检测开发方面拥有丰富的经验。他们将监督一组从事上述职能的科研助理。

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.