University of New Mexico Center for Molecular Discovery

描述（由申请人提供）：新墨西哥大学分子发现中心（UNMCMD）是一个专注于多路HT流式细胞术的专业中心，延续了新墨西哥分子文库筛选中心（U54MH074425）和生物医学研究合作伙伴关系（R24EB000264）。我们发明了HT流式细胞术平台HyperCyt¿并将其引入MLSCN。我们的发现工具能够进行配体结合和/或蛋白质相互作用（PPI）的均匀分析，多参数或高含量分析，以及细胞反应或结合的实时测量。我们在11分钟内分析了384孔板。在MLSMR上完成的筛选已经产生了用于细胞（分子和表型）和基于珠子的靶标的探针。经验表明，大多数目标可以显示在流式细胞术兼容的格式。通过创建悬浮粒子阵列，目标可以高度复用或在复杂的细胞群上执行，而不会损失吞吐量。我们的团队发表了100多篇论文，20多项发明，出版了关于生物技术流式细胞术和虚拟筛选的书籍，并在全球发表了100多篇口头演讲。我们拥有150多年的流式细胞术经验，包括在生物化学、细胞和分子生物学方面的应用，以及酵母靶标的双重专业化。我们中的一个人在工业HTS方面有20年的经验，为150个新目标提供HTS。我们的核心能力包括：1)有效的外联和伙伴关系；2)确定和发展创新目标；3)实施外部初级和二级分析；4)多路目标的生产模式筛选；5)数据上传到PubChem。我们在将显像剂和同位素整合到MLPCN方面具有独特的优势。我们打算在所有的活动中进行创新。通过外展，我们将为MLPCN创建和维护多种检测方法。检测开发将包括但不限于酵母、真核生物和分析目标。我们将为MLPCN的分析目标和探针（包括化合物溶解度）创建优先级和实施伙伴关系的机制。我们将创建工具来分析和可视化多个HTS数据集。我们将加强和维护与目标供应商和化学专业中心的网络协作工具，以进行筛选和跟踪，并在MLPCN内进行协作分析和化合物溶解度。一个中心驱动项目的重点是提高吞吐量（从384孔格式到1536孔格式），并通过利用我们中心与商业合作伙伴最近的设计和工程突破来提高高温流式细胞仪的性能。通过合作外展，我们将评估来自洛斯阿拉莫斯国家实验室P41国家流式细胞术资源的新发现技术。第二个中心驱动项目开发了酵母靶点工具箱，如PPI，途径分析，蛋白质- dna相互作用，以及一个通用的，多重酵母双杂交发现平台。

DESCRIPTION (provided by applicant): The University of New Mexico Center for Molecular Discovery (UNMCMD), a specialty center focusing on multiplexed, HT flow cytometry, continues the New Mexico Molecular Libraries Screening Center (U54MH074425) and a Biomedical Research Partnership (R24EB000264). We invented the HT flow cytometry platform HyperCyt¿ and introduced it to the MLSCN. Our discovery tools enable homogeneous analysis of ligand binding and/or protein-protein interaction (PPI), multiparameter or high content analysis, and real-time measurements of cell response or binding. We analyze a 384 well plate in 11 min. Completed screens on the MLSMR have produced probes for cell (molecular and phenotypic) and bead-based targets. Experience indicates that most targets can be displayed in a flow cytometry compatible format. By creating a suspension array of particles, targets can be highly multiplexed or performed on complex cell populations without loss of throughput. Our team has produced >100 publications, >20 inventions, books on Flow Cytometry for Biotechnology and Virtual Screening, and >100 oral outreach presentations world-wide. We have >150 years of flow cytometry experience that includes applications in biochemistry, and cell and molecular biology compatible with a dual specialization in yeast targets. One of us has >20 years of experience in industrial HTS for >150 novel targets. We have core capabilities that include 1) effective outreach and partnership; 2) identifying and developing innovative targets; 3) implementing external primary and secondary assays; 4) production mode screening of multiplexed targets; and 5) data upload to PubChem. We are uniquely positioned to integrate imaging agents and isotopes into the MLPCN. We intend to innovate in all of our activities. Through outreach, we will create and maintain a pipeline of multiplex assays for the MLPCN. Assay development will include, but not be limited to, yeast, eukaryotic, and profiling targets. We will create mechanisms to prioritize and implement partnerships for profiling targets and probes, including compound solubility, for the MLPCN. We will create tools to analyze and visualize multiplex HTS data sets. We will enhance and maintain collaborative tools for networking with target providers and Chemistry Specialty Centers for screening and follow up, and within the MLPCN for collaborative profiling and compound solubility. One Center Driven Project focuses on increasing throughput (from 384 to 1536 well format) and improving the performance of HT flow cytometry by exploiting recent design and engineering breakthroughs in our Center along with commercial partners. Through collaborative outreach, we will evaluate new discovery technologies emerging from the Los Alamos National Labs P41 National Flow Cytometry Resource. A second Center Driven Project develops a toolbox for yeast targets such as PPI, Pathway analysis, protein-DNA interactions, and a universal, multiplex yeast two-hybrid discovery platform.