Science and Technology Partnerships

新型亲和试剂的开发：在过去的财政年度，科学和技术伙伴关系办公室（OSTP）继续支持一项倡议，即生产高亲和试剂，作为癌症发展过程中改变的分子通路的分子询问工具。与两家生物技术公司（Beckton Dickinson Pharmingen和Rockland Immunochemicals）的合作，已经产生了近200种新型亲和试剂（多克隆和单克隆抗体），针对数百种CCR感兴趣的关键癌症相关靶点，而CCR研究人员无需支付任何费用。这些伙伴关系为CCR和NCI节省了100多万美元。通过这些合作伙伴关系开发的抗体包括：1)没有市售抗体的新型候选蛋白质；2)存在市售抗体但不符合研究者要求的已知蛋白质；3)具有磷酸化位点的蛋白质可能在癌症发展过程中改变的途径中起重要作用。所有由参与CCR的研究人员生成的抗体特性数据，都可以通过OSTP与高级生物医学计算中心（ABCC）合作开发的网站提供给相关公司。当抗体被商业化时，每家公司都会在他们的营销材料中使用这些数据。本财年将与Epitomics公司展开第三次合作，生产兔单克隆抗体。已知这些抗体比小鼠单克隆或兔多克隆抗体更稳定，具有更高的亲和力。OSTP与Epitomics签订了一份合同，以大幅降低成本（5500美元，而目录价格为20,000美元）使用其抗体生产管道。与其他合作项目类似，CCR研究人员将被要求对抗体进行表征，并将数据提供给Epitomics进行验证和商业化。发现新的蛋白质-蛋白质相互作用：OSTP支持许多项目来定义新的与癌症相关的蛋白质-蛋白质相互作用和细胞信号网络。例如，OSTP管理了一个主要的筛选项目，以识别和表征CCR中正在研究的大量癌症相关蛋白的新结合伙伴。ccr与Myriad Genetics建立了广泛的合作伙伴关系，以访问他们基于酵母双杂交（Y2H）方法的蛋白质-蛋白质相互作用大规模鉴定的自动化过程。CCR和Myriad之间的大规模合作产生了大量数据（超过1800种新的蛋白质相互作用已转移给CCR研究人员），这些数据允许描述以前未表征的信号通路，并更好地了解癌症的分子基础。从这些筛选中获得的数据已通过OSTP与ABCC合作开发的一个网站提供给CCR调查人员。促进获得基因组技术：OSTP一直在评估所有商业上可用的微阵列和其他高通量基因组技术平台。为了使CCR研究人员更容易获得最新进展，OSTP与提供基因组分析技术和服务的公司（Affymetrix, NimbleGen, Agilent, Illumina, GenUs， SABiosciences等）建立了许多合同和定价安排。这些协议大大降低了CCR研究人员获取这些技术的成本和效率。已经建立了一项补贴计划，为从这些公司购买的所有微阵列或要求提供全方位微阵列分析服务的CCR社区提供50%的支付。这种资助机制有助于扩大CCR实验室可用的有限研究资金，并允许我们的研究人员进行原本可能成本过高的实验。许多资助的项目都在顶级期刊上发表了重要论文。最近，OSTP一直在协调CCR的工作，以获得超高通量的下一代测序技术。OSTP参与了安装在两个CCR实验室的两台Illumina/Solexa基因分析仪的收购的所有方面。OSTP将为研究人员提供补贴资金，使许多CCR实验室能够使用这项非常昂贵的技术。OSTP还与SAIC-Frederick， Inc.合作，在位于马里兰州盖瑟斯堡的NCI先进技术中心（ATC）建立一个新的测序设施。该设施将在下一财政年度开始运行，将使所有NCI研究人员广泛使用下一代测序技术。生物信息学和生物统计学分析工具：为了应对CCR快速增长的管理和分析大量基因组和蛋白质组学数据的需求，OSTP与一些生物信息学公司建立了合作关系。为了显著节省NCI的成本，OSTP代表所有NCI研究人员谈判了各种许可协议，以便普遍获得用于微阵列实验、arrayCGH研究、蛋白质组学分析研究、基因组分析和基因筛选的生物信息学和统计分析的复杂工具。此外，OSTP还为所有NCI提供了一些用于研究通路和生物关联网络的软件应用程序。CCR/NCI集成和协作知识环境：为了解决在数量不断增长和不断扩大的公共和私人数据库中查询相关的复杂性，OSTP已经建立了一个新的项目，与Sophic系统联盟和Biomax合作开发CCR/NCI集成和协作知识环境。Biomax开发的软件使生物和生物医学数据和信息之间的复杂关系可视化。它的设计目的是通过对存储在中央存储库中的信息进行注释来使知识制度化。知识环境的配置是为了支持对不同类型的癌症、数据来源和研究策略的研究。CCR/NCI实验室正在根据各自的研究需求配置Biomax软件，以确定其对中心癌症研究的益处。研究领域包括大肠癌和肝癌、神经母细胞瘤、放射肿瘤学和神经肿瘤学。每个实验室都需要对其软件实例进行配置，以适应该实验室进行的研究类型。通用CCR知识环境被配置为提供对集成到单个用户界面中的35个公共数据库的访问，使科学家能够查询广泛的数据源。通过基因组学、蛋白质组学、途径分析和临床研究获得的信息被组合成复杂关系的图形表示。通用CCR知识环境的未来计划包括集成额外的数据库、基因组和蛋白质组学分析工具和软件。

Development of Novel Affinity Reagents: During the past fiscal year, the Office of Science and Technology Partnerships (OSTP) has continued to support an initiative for generating high affinity reagents to serve as tools for molecular interrogation of pathways that become altered during cancer development. Partnerships with two biotechnology companies, Beckton Dickinson Pharmingen and Rockland Immunochemicals, have led to the creation of nearly 200 novel affinity reagents (polyclonal and monoclonal antibodies) against hundreds of key cancer-related targets of interest to the CCR at no cost to CCR investigators. These partnerships represent savings of more than one million dollars to CCR and the NCI. The antibodies that have been developed through these partnerships include: 1) novel candidate proteins for which no commercially available antibodies exist; 2) known proteins for which commercially available antibodies exist but fail to meet investigators' requirements; and 3) proteins with phosphorylation sites that may be of importance in pathways that are altered during cancer development. All of the antibody characterization data generated by participating CCR investigators is made available to the companies involved through a Web site developed in a collaboration between the OSTP and the Advanced Biomedical Computing Center (ABCC). Each company uses this data in their marketing material when the antibodies are released for commercialization. A third collaboration will begin this fiscal year with the company, Epitomics, for production of rabbit monoclonal antibodies. These antibodies are known to be much more stable and have higher affinities than mouse monoclonal or rabbit polyclonal antibodies. The OSTP negotiated a contract with Epitomics to access their antibody production pipeline at a significantly reduced cost ($5,500 versus $20,000 from the catalog price). Similar to the other collaborative programs, CCR investigators will be required to characterize the antibodies and make data available to Epitomics for validation and commercialization. Discovery of Novel Protein-Protein Interactions: The OSTP supported a number of programs for defining novel cancer relevant protein-protein interactions and cell signaling networks. For example, OSTP managed a major screening program to identify and characterize novel binding partners to a large number of cancer-related proteins currently under investigation within the CCR. A CCR-wide partnership with Myriad Genetics was developed to access their automated process for the large-scale identification of protein-protein interactions that is based on the yeast two-hybrid (Y2H) methodology. This large-scale effort between CCR and Myriad generated a host of data (over 1,800 novel protein interactions have been transferred to CCR investigators) that are permitting the delineation of previously uncharacterized signaling pathways and a better understanding of the molecular basis underlying cancer. The data derived from these screens has been made available to CCR investigators through a Web site developed in collaboration between OSTP and the ABCC. Facilitating Access to Genomic Technologies: The OSTP has been evaluating all commercially available platforms for microarray and other high throughput genomic technologies. To make the latest advances easily accessible to CCR researchers, the OSTP has established a number of contracts and pricing arrangements with companies providing genomic profiling technologies and services (Affymetrix, NimbleGen, Agilent, Illumina, GenUs, SABiosciences, etc). These agreements have led to far lower cost and an efficient and easy way for CCR investigators to access these technologies. A subsidy program has been established providing 50% payment to the CCR community for all microarrays that are purchased from these companies or full-service microarray analysis that is requested. This funding mechanism has helped to extend the limited research dollars available to CCR laboratories and has permitted our researchers to conduct experiments that might otherwise be cost prohibitive. Many of the funded projects have led to important publications in top tier journals. Most recently, the OSTP has been coordinating CCR's efforts to access the ultra high-throughput, next-generation sequencing technologies. OSTP was involved in all aspects of acquisition of two Illumina/Solexa genetic analyzers that were installed in two CCR laboratories. The OSTP will be providing investigators with subsidy funds to make this very expensive technology accessible to many CCR labs. The OSTP is also working with SAIC-Frederick, Inc. to create a new sequencing facility to be located at the NCI's Advanced Technology Center (ATC) in Gaithersburg, MD. This facility, which will begin operation during the next fiscal year, will make next-generation sequencing technology broadly available to all NCI researchers. Tools for Bioinformatics and Biostatistics Analysis: In response to CCR's rapidly growing need to manage and analyze large sets of genomic and proteomic data, the OSTP has developed several partnerships with bioinformatics companies. At significant cost savings to NCI, OSTP negotiated a variety of license agreements on behalf of all NCI researchers for universal access to sophisticated tools for bioinformatic and statistical analysis of microarray experiments, arrayCGH studies, proteomic profiling studies, genomic analysis, and genetic screens. In addition, the OSTP has made a number of software applications for the investigation of pathways and biological association networks available to all of NCI. A CCR/NCI Integrated and Collaborative Knowledge Environment: To address the complexities associated with querying across the growing number and ever-expanding public and private databases, the OSTP has established a new program to develop a CCR/NCI integrated and collaborative knowledge environment in collaboration with Sophic Systems Alliance and Biomax. Software developed by Biomax enables the visualization of complex relationships between biological and biomedical data and information. It is designed to institutionalize knowledge by enabling the annotation of information stored in a central repository. The Knowledge Environment was configured to support research on different types of cancer, sources of data, and research strategies. The CCR/NCI laboratories are configuring the Biomax software according to their individual research requirements to determine its benefits to cancer research at the Center. The areas of research include colorectal and liver carcinogenesis, neuroblastoma, radiation oncology, and neuro-oncology. Each lab requires configuration of their software instance that is tailored to the type of research conducted in that lab. The Common CCR Knowledge Environment was configured to provide access to 35 public databases integrated into a single user interface, allowing scientists to query a wide range of data sources. Information derived through genomics, proteomics, pathway analysis, and clinical studies are combined into graphical representations of complex relationships. Future plans for the Common CCR Knowledge Environment include the integration of additional databases, genomic and proteomic analysis tools, and software.