Burnham Center for Chemical Genomics

描述（由申请人提供）：伯纳姆化学基因组学中心，在MLSCN阶段和令人印象深刻的机构支持有着良好的记录，准备为分子库探针生产中心网络（MLPCN）作为一个综合筛选中心做出贡献。伯纳姆中心可能是所有网络中心中最多样化的，不仅提供基本的HTS和uHTS能力和出色的药物化学，而且还提供（i）基于多光谱高通量显微镜（HTM）的表型筛选的先进开发;（ii）用于化合物类似物快速多平行合成的微流体技术;（iii） 使用基于片段的方法进行基于NMR的化合物优化的强大能力;（iv）先进的3D计算建模和基于结构的化合物优化能力;以及（v）探索性药理学。在MLPCN阶段的准备工作中，为扩大该中心的能力提供了额外的机构支持，包括额外的uHTS系统。总之，伯纳姆中心随时准备推进NIH路线图的使命进入全面生产阶段。伯纳姆中心分为5个单元，支持MLPCN的用户驱动目标，以及2个中心驱动项目，旨在以综合方式推进化学基因组学领域。支持MLPCN核心使命的是以下单位：（1）检测开发、调整和实施，包括高含量（HC）检测和软件开发方面的世界级专业知识;（2）HTS，随时准备处理MLPCN现在的通量和HTS需求的多样性，并具有扩展能力以满足任何未来的通量需求;（3）化学，其中包括专门从事（a）药物化学、（B）化学信息学、（c）用于化合物验证和优化的基于NMR的技术和（d）探索药理学的综合子单元;（4）信息学，具有强大的支持关系数据库，可链接到800多万种商业化合物，并具有多TB的存档能力，以支持人道主义协调员的应用;（5）行政管理。在MLSCN阶段建立了实现这些目标的基础设施，包括数据和资源共享的各个方面;与检测提供商，其他网络中心和NIH的协作互动;机构间知识产权管理;以及内部中心治理，从而使我们的中心能够立即提供结果。该中心主导的项目侧重于：（1）应用连续流微反应器技术解决药物化学瓶颈，将化合物模拟的时间和成本降低到当前标准的一小部分;以及（2）开发用于HC筛查（HCS）的先进SD成像技术，包括（a）3D细胞培养系统;（B）创新的HTM仪器;以及（c）新型成像技术。 算法和软件，这将使新一代的化学基因组学应用，推动技术应用超越单细胞培养。:

DESCRIPTION (provided by applicant): The Burnham Center for Chemical Genomics, with a strong track record in the MLSCN phase and impressive institutional support, is poised to contribute to the Molecular Libraries Probe Production Centers Network (MLPCN) as a Comprehensive Screening Center. The Burnham Center is probably the most diverse of all Network Centers, offering not only basic HTS and uHTS capabilities and outstanding medicinal chemistry, but also (i) advanced development of phenotypic screens based on multi-spectral high throughput microscopy (HTM); (ii) microfluidics technology for rapid multi-parallel synthesis of compound analogues; (iii) strong capabilities in NMR-based compound optimization using fragment-based approaches; (iv) advanced 3D computational modeling and structure-based compound optimization capabilities; and (v) exploratory pharmacology. In preparation for the MLPCN Phase, additional institutional support was provided for expanding the capabilities of the Center, including an additional uHTS system. Altogether, the Burnham Center stands ready to advance the mission of the NIH Roadmap into full Production Phase. The Burnham Center is organized into 5 Units that support the User-driven goals of MLPCN, and 2 Center-driven projects aimed at advancing the field of chemical genomics in an integrated manner. Supporting MLPCN's core mission are the following Units: (1) Assay development, adaptation and implementation, which includes world-class expertise in high-content (HC) assay and software development; (2) HTS, ready to handle now the throughput and diversity of HTS demands of MLPCN, with capacity to expand for meeting any future throughput demands; (3) Chemistry, which includes integrated subunits devoted to (a) medicinal chemistry, (b) cheminformatics, (c) NMR-based technologies for compound validation and optimization, and (d) exploratory pharmacology; (4) Informatics, with a powerful supporting relational database with links to > 8 million commercially available compounds and multi-Terabyte archiving capacity for supporting HC applications; and (5) Administration. The infrastructure for accomplishing these goals was established during the MLSCN phase, including all aspects of data and resource sharing; collaborative interactions with assay providers, other Network Centers and NIH; inter-institutional IP management; and internal Center governance, thus positioning our Center to deliver results immediately. The Center-driven projects focus on: (1) applications of continuous-flow microreactor technology for addressing the medicinal chemistry bottleneck, reducing the time and costs of compound analoging to a fraction of current standards; and (2) development of advanced SD-imaging technologies for HC screening (HCS), including (a) 3D cell culture systems; (b) innovative HTM instrumentation; and (c) novel imaging algorithms and software, which will enable a new generation of chemical genomics applications that push technology applications beyond monolaver cell cultures. :