Sanford-Burnham Center for Chemical Genomics

伯纳姆化学基因组学中心在MLSCN阶段有着良好的记录和令人印象深刻的机构支持，准备作为一个全面的筛选中心为分子文库探针生产中心网络(MLPCN)做出贡献。伯纳姆中心可能是所有网络中心中最多样化的，它不仅提供基本的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)用于快速多平行合成化合物类似物的微流体技术；(Iii) 在使用基于片段的方法进行基于核磁共振的化合物优化方面具有很强的能力；(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)探索药理学。为筹备MLPCN阶段，为扩大该中心的能力提供了额外的机构支助，包括一个额外的uHTS系统。总之，伯纳姆中心随时准备将NIH路线图的使命推进到全面生产阶段。 伯纳姆中心由5个支持MLPCN用户驱动目标的单位和2个旨在以综合方式推进化学基因组学领域的中心驱动项目组成。支持MLPCN的核心任务的单位如下：(1)分析开发、适应和实施，包括在高含量(HC)分析和软件开发方面的世界级专业知识；(2)HTS，现在可以满足MLPCN对HTS需求的吞吐量和多样性，有能力扩展以满足未来的任何吞吐量需求；(3)化学，包括致力于(A)药物化学、(B)化学信息学、(C)基于核磁共振的化合物验证和优化技术，以及(D)探索药理学；(4)信息学，具有强大的支持性关系数据库，可链接到800万种可商业使用的化合物和支持HC应用程序的多TB存档能力；以及(5)行政管理。实现这些目标的基础设施是在MLSCN阶段建立的，包括数据和资源共享的所有方面；与分析提供商、其他网络中心和NIH的协作互动；机构间知识产权管理；以及中心内部治理，因此我们的中心定位为立即交付结果。中心推动的项目重点是：(1)连续流动微反应器技术的应用，以解决药物化学瓶颈，将化合物模拟的时间和成本减少到当前标准的一小部分；(2)开发用于HC筛查的先进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)新型成像算法和软件，这将使新一代化学基因组学应用能够推动技术应用超越单细胞培养。

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.